Cell Transplantation

Bronchiolitis obliterans syndrome (BOS) is a severe pulmonary complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with limited therapeutic options once refractory to standard immunosuppression. We conducted a pilot study from January 2018 to December 2024, enrolling consecutive patients with BOS defined by NIH criteria who failed glucocorticoids and calcineurin inhibitors for ≥4 weeks. Sixteen patients received salvage therapy with ruxolitinib 5 mg twice daily and nintedanib 150 mg twice daily (RN cohort) in continuous 28-day cycles for up to six cycles, while 37 contemporary patients served as controls. At baseline, NIH lung scores in the RN cohort were 18.8% NIH 1, 18.8% NIH 2, and 62.5% NIH 3. The median number of treatment cycles was 3.5 (range, 1–6). At 3 months, 11 patients (68.8%) achieved ≥10% improvement in %FEV1 from baseline (median = 26.5%, range = 15.6%–58.2%). By NIH lung response criteria, the overall response rate (ORR) was 62.5% (12.5% complete response, 50.0% partial response) in the RN cohort versus 13.5% (5.4% complete, 8.1% partial) in controls. Notably, hematologic toxicities were less frequent with RN therapy than in controls. These findings suggest that low-dose ruxolitinib combined with nintedanib is an effective and well-tolerated salvage regimen for BOS after allo-HSCT and warrant confirmation in a prospective phase II study.

Myocardial infarction (MI), mainly caused by coronary artery occlusion, remains a leading cause of death worldwide. Although many patients survive after emergency treatment, chronic MI often develops, underscoring the need for effective therapies. This study evaluated the therapeutic potential of human umbilical mesenchymal stromal cells (HUMSCs) in a rat model with chronic MI. MI was induced by permanent ligation of the left anterior descending artery. Seven days post-ligation, 4×10⁶ HUMSCs were transplanted into the peri-infarct myocardium, while an additional 2.5×10⁷ HUMSCs were introduced into the mediastinal space around the ligation site. Successful model establishment was confirmed by elevated cardiac biomarkers and characteristic electrocardiographic changes. Echocardiography and magnetic resonance imaging demonstrated significant impairments in myocardial strain dynamics, reduced ejection fraction, and diminished fractional shortening, all of which improved following HUMSC transplantation. The transplantation also reduced macrophage infiltration, increased M2 macrophage polarization, suppressed fibroblast activation, attenuated fibrosis, and promoted angiogenesis, ultimately preserving cardiomyocytes and improving cardiac function. The transplanted HUMSCs were detected in rat’s myocardium without differentiating into cardiomyocytes or endothelial cells. These findings suggest that adequate HUMSC transplantation offers a promising therapy to attenuate progression of chronic MI or heart failure.

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Liver transplantation is the only curative option for end-stage liver disease, but its applicability is limited by donor shortages. Hepatocyte transplantation offers a promising alternative, particularly for pediatric acute liver failure, yet its success relies on the availability of viable cells. Cryopreservation enables off-the-shelf use, though long-term storage may impair cell quality. This study investigates whether cryostorage duration, donor characteristics, and organ retrieval parameters affect the viability and functionality of cryopreserved primary human hepatocytes (PHHs). We conducted a retrospective analysis of 144 thawing events across 81 GMP-grade hepatocyte batches, cryopreserved for up to 14 years. Donor age ranged from 3 days to 70 years. Viability and functionality were assessed using MTT assays, albumin and urea secretion, and CYP450 activity. Linear regression was used to analyze correlations (P < 0.05 considered significant). The cryopreservation duration had no significant impact on hepatocyte viability or function, confirming that clinical-grade PHHs can maintain quality for up to 14 years. However, donor age correlated negatively with post-thaw viability (R² = 0.035, P = 0.029), yield (R² = 0.039, P = 0.041), and metabolic activity (R² = 0.278, P = 0.008), while showing a positive correlation with induced ethoxy resorufin O-demethylation (EROD) function (R² = 0.432, P = 0.020). Donor body mass index (BMI) showed significant negative associations with viability (R² = 0.075, P = 0.003), yield (R² = 0.069, P = 0.011), and metabolic activity (R² = 0.267, P = 0.019). Cold ischemia time (CIT) showed a weak negative correlation with viability (R² = 0.151, P < 0.0001), particularly when CIT exceeded ~10 h and viability fell below 60%. Clinical-grade cryopreserved hepatocytes retain viability and function for over a decade. CIT, donor BMI, and age impacted post-thaw quality, while warm ischemia time (WIT), within our current criteria, and storage duration had minimal impact. These findings support refining donor selection to improve cryopreservation outcomes.

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Autoimmune diseases (AIDs) are a class of diseases caused by autoimmune intolerance, which can be divided into systemic and organ-specific diseases. AIDs affect approximately 10% of the global population and rank among the leading causes of disability and mortality. At present, immunosuppressive agents are the first choice for the treatment of AIDs. B-cell-targeted therapies—particularly CD20 monoclonal antibodies—have brought new hope for systemic AIDs, yet a subset of patients still respond poorly. As a rapidly developing cellular immunotherapy technology, Chimeric antigen receptor T cell (CAR-T) plays an important role in the treatment of hematological malignancies. CAR-T targeting B-cell-specific antigens can rapidly deplete circulating B cells, thereby reducing the formation of autoantibodies, which has become the basis for research on CAR-T in the treatment of autoimmune diseases. Currently, many studies are underway, and CAR-T and its derivative therapies bring new hope for the treatment of autoimmune diseases.

The effective application of allogeneic mesenchymal stem cells (MSCs) has the potential to enhance cartilage regeneration. This study aimed to evaluate the therapeutic efficacy of intra-articular (IA) injections of small umbilical cord–derived fast proliferating cells (smumf cells) combined with magnesium (Mg²⁺) in a rat model of full-thickness cartilage defects (FTDs). Adhesion of smumf cells was assessed on type I collagen-coated surfaces in vitro, in an uncontained ex vivo model, and via cell tracking in a rat FTD model. Therapeutic efficacy was evaluated using histological analyses of macroscopic and microscopic in vivo (at 4 and 8 weeks, n = 6). Mg²⁺ improved the adhesion of smumf cells by up to 1.89-fold in the ex vivo model, and by 2.80-fold in cell tracking. A single injection of smumf cells alone improved histological scores by 2.33-fold at 4 weeks, whereas the combination with Mg²⁺ resulted in further improvements in both macroscopic (1.30-fold) and microscopic (1.26-fold) scores at 8 weeks. Moreover, the smumf cells + Mg²⁺ group showed significant increases in tissue thickness (1.40-fold), safranin O-positive area (2.88-fold), and type II collagen synthesis (1.22-fold) in rat model. This study demonstrates that a single IA injection of smumf cells combined with Mg² enhances cell homing and functional adhesion at the defect site, thereby promoting superior cartilage regeneration compared with smumf cells alone.

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Hypothyroidism, a prevalent endocrine disorder characterized by insidious onset and prolonged progression, leads to metabolic slowdown and multiorgan dysfunction, significantly compromising patients’ quality of life. While hormone replacement therapy improves most patients’ serum thyroid function, it faces limitations, including individual response variations, lifelong medication requirements, and potential risks, with no reversal of existing tissue damage. In recent years, the mesenchymal stem cells (MSCs) and their derivatives have gained prominence in immunomodulation and regenerative medicine because of their abundant sources, low immunogenicity, potent paracrine effects, and multidirectional differentiation capabilities for tissue repair. Their unique advantages in modulating the immune microenvironment, promoting angiogenesis, reducing fibrosis, and stimulating endogenous cell regeneration offer novel strategies to overcome treatment bottlenecks in hypothyroidism and its complications, effectively repairing thyroid and multiorgan damage in animal models. This review synthesizes literature from the PubMed and Web of Science databases, incorporating relevant basic research and clinical trials. This study examined the systemic impacts of hypothyroidism, evaluated the experimental and clinical roles of the MSCs in thyroid tissue reconstruction and organ protection, and analyzed molecular mechanisms, including immune regulation, the antioxidant stress response, anti-apoptosis, and cellular function restoration. Clinical application potential is assessed alongside critical challenges such as standardized preparation, long-term safety, in vivo homing efficiency, and large-scale production.

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Xenogeneic cells isolated from safe animal tissues and expanded ex vivo hold potential as immunotherapeutic agents capable of stimulating the body’s immune system to treat cancers. This study aimed to evaluate the in vivo safety and immunological effects of xenogeneic mammary cells of porcine origin (XMC), ensuring that their local administration is a safe medical intervention for breast cancer treatment. The safety of local XMC treatment was assessed by injecting varying doses of these cells into the abdominal mammary fat-pad tissues as prime and booster shots. Over a 28-day observation period, the tested dose range showed no significant changes in body weight or organ weight, and histopathological analysis revealed no pathological alterations in liver or kidney tissues. No abnormal findings were observed in hematology and serum biochemistry parameters. However, a dose-dependent periductal inflammation and lymphoid tissue infiltration were observed at the injection site. To further assess immune responses to xenogeneic cells, we evaluated their ability to stimulate immune cell proliferation and cytokine secretion in co-cultures with mouse splenocytes and human leukemia cell lines. Cell proliferation was measured by flow cytometry, and cytokine was analyzed using the ELISA method. Co-cultures of mouse splenocytes, KG-1, or Jurkat cells with XMCs elicited a proliferative response and increased secretion of cytokines, including interleukin-2 and interferon gamma, which are involved in immune rejection and antitumor activity. Physical interactions between immune cells and xenogeneic cells have also been demonstrated. The mouse safety study and cell-based bioassay results indicate that XMCs were safe within the tested dose range in this preclinical in vivo assessment, and their immune-stimulatory effects were clearly measurable.

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Diabetes mellitus (DM) is a metabolic disorder with chronic hyperglycemia due to insulin deficiency and/or impaired insulin action. DM is a common disease, but it often threatens a patient’s quality of life. Cellular replacement therapy using insulin-producing cells is a promising therapy for severe DM because of the proper provision of internal insulin according to a change in blood glucose concentrations. This Special Collection, “Cellular Replacement Therapy for Diabetes,” was planned to appeal the current status and present novel translational trials of this therapy. Ten specialists presented their research, which attempted to overcome three limitations of the current cellular replacement therapy, including the regulation of immunity, limited donor supplies, and establishment of a preferable transplant site for cellular replacement therapy. Regarding regulation of immunity, potential of mesenchymal stem cells and immunomodulatory splenocytes is clarified. Regarding alternative donors, the current status of porcine islet xenotransplantation and therapy using multipotent stem cell–derived cells is introduced. And regarding transplant site, possibility of liver surface and subcutaneous tissue is elucidated.

γδ T lymphocytes and NK cells are effective to kill tumors or viral-infected cells avoiding graft versus host disease (GvHD), thus they have attracted high interest as potential tool for adoptive cell therapy. We generated an advanced therapy medicinal product (ATMP) composed of mature γδ T and NK cells to provide an innovative tool to protect patients against tumor relapse and life-threatening infection after haploidentical hematopoietic stem cell transplantation. The ATMP was manufactured and validated in a GMP facility and was obtained from leukapheresis stimulated with zoledronic acid and IL-2, afterward depleted of αβ T lymphocytes using the CliniMACS Prodigy. The ATMP is characterized by high homogeneity, cell viability, cytotoxic abilities, stability after cryogenic preservation, and it was virtually free of αβ T and B lymphocytes. Both NK and γδ T cells were activated and characterized by high expression of cytotoxic and activating receptors including NKG2D, CD16, NKp30, NKp44, and NKp46. Furthermore, γδ T lymphocytes and NK cells were cytotoxic against myeloid leukemia or neuroblastoma cells. In conclusion, we implemented a novel ATMP to be shortly translated into clinical practice, which may be used in the post-transplant phase as efficacious immunotherapy in neuroblastoma and leukemic pediatric patients.

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Islet cell transplantation holds great promise for restoring glycemic control in patients with type 1 diabetes. However, its long-term efficacy remains limited due to poor islet survival, immune rejection, and insufficient vascularization. Mesenchymal stem cells (MSCs) have emerged as potent biological adjuvants capable of addressing these challenges through a range of molecular mechanisms. MSCs secrete a variety of growth factors, immunoregulatory and pro-angiogenic molecules that enhance viability of islet cells, modulate the immune response, promote neo-angiogenesis and enhance islet engraftment. In addition, MSC-derived exosomes (MSC-Exos) have been identified as key mediators, delivering regulatory microRNAs and proteins that replicate many of the beneficial effects of MSCs in a cell-free format. MSC-Exos act as small RNA carriers and immunomodulators, promoting islet survival and functional integration. Understanding the molecular interplay between MSCs, their exosomes, and the islet microenvironment provides crucial insights for the development of advanced co-transplantation strategies. Accordingly, in this review article, we summarized current knowledge about molecular mechanisms that are responsible for MSC-dependent improvement of islet cell transplantation and we highlighted the translational potential of MSC and MSC-Exos-based approaches in improving islet graft outcomes for type 1 diabetes.

Enhancer–promoter (E-P) interactions are central to cell-type-specific transcriptional programs, yet the molecular machinery that establishes and maintains these loops has remained poorly defined. A recent study by Jiang et al, published in Nature Genetics, presents a series of transformative discoveries that redefine our understanding of E-P interactions and their role in gene regulation and cell fate determination. The research introduces LoopID, a chromatin-interaction-based proteomic platform that, for the first time, enables systematic identification of protein components, termed the “looposome,” localized specifically at chromatin looping anchors. Using LoopID, they profile the “looposome” in mouse embryonic stem cells (ESCs) and uncover an unexpected, catalytic-independent role for the histone demethylase JMJD2 (KDM4) in organizing chromatin architecture through phase-separated condensates. Beyond mechanism, the study demonstrates that targeted assembly of JMJD2 condensates at defined genomic loci can engineer E-P interactions driving cellular reprogramming toward pluripotent and two-cell-like states. Together, these findings represent not only a major technical advance but also a conceptual leap—establish LoopID as a foundational technology for dissecting chromatin structure, introduce a new conceptual framework for epigenetic regulators as structural organizers, and provide a powerful strategy to manipulate cell fate by rewiring three-dimensional (3D) genome architecture.

Enterocutaneous fistula (ECF) traditionally relies on surgical treatment and lacks effective therapies to promote tissue regeneration. This study constructed a composite system based on hypoxia-preconditioned human umbilical cord mesenchymal stem cell–derived exosomes loaded onto a gelatin sponge (GS Hypo-Exos), aiming to explore its potential application in ECF treatment. First, systematic characterization of exosomes was performed: transmission electron microscopy, nanoparticle tracking analysis, western blot, and flow cytometry confirmed successful exosome extraction. Material evaluation indicated that the gelatin sponge exhibited high porosity and good biocompatibility. Scanning electron microscopy confirmed successful loading of exosomes onto the sponge surface, and in vitro release experiments showed that GS Hypo-Exos enabled sustained release of VEGF and IGF-1, with release behavior superior to the normoxic control group. Small-animal in vivo imaging further demonstrated that exosome-loaded gelatin sponge could be retained locally at the fistula site for up to 21 days post-surgery. In the Sprague–Dawley rat ECF model, the GS Hypo-Exos treatment group (group C) showed superior healing effects compared with the normoxic exosome group: fistula area and circumference were significantly reduced, and animal weight recovery was the fastest. Serological analysis revealed that this group had the lowest level of inflammatory factor TNF-α and the highest level of anti-inflammatory factor IL-4. Local tissue levels of VEGF and TGF-β1 were significantly increased. Histopathological examination indicated reduced inflammatory cell infiltration and increased collagen fiber proliferation in group C. Regarding molecular mechanisms, real-time quantitative polymerase chain reaction and western blot results consistently showed significantly upregulated expression of the cell proliferation marker Ki67 and markedly downregulated expression of the apoptosis-related protein Caspase-3 in group C. In summary, GS Hypo-Exos effectively promotes structural and functional repair of ECF through synergistic sustained-release delivery and immunomodulation, providing experimental evidence for the development of novel ECF repair strategies.

The natural cycle of hair growth and shedding is continuous. However, an abnormal rate of hair regrowth can signal alopecia, a condition characterized by excessive hair loss and thinning. Alopecia is a common dermatological concern globally, affecting individuals across all ages and sexes, often resulting in psychological distress and diminished quality of life. Despite the availability of various current therapy options such as minoxidil, finasteride, JAK inhibitors, low-level laser, and hair transplantation, these approaches are often limited by variable efficacy or side effects. Consequently, there is growing research interest in regenerative therapies using stem cells as a promising avenue to overcome these shortcomings. Stem cells, characterized by their ability to self-renew and differentiate into multiple cell types, offer the potential to promote hair follicle regeneration. Among the different stem cell types under investigation, hair follicle stem cells (HFSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) have attracted attention due to their regenerative capabilities and immunomodulatory properties. This narrative review explores the underlying causes of alopecia, current and emerging therapies, particularly emphasizing the therapeutic potential of stem cells and their specialized roles in promoting a supportive environment for the hair follicle and scalp. It also examines ongoing clinical and preclinical studies involving stem cell–based therapies for hair loss, aiming to assess their feasibility as future clinical solutions for alopecia.

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To investigate the efficacy and safety of MTBF as conditioning regimen for salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed or refractory acute myeloid leukemia (R/R AML). We conducted a single-arm prospective clinical trial (NCT06385808). The main outcome was cumulative incidence of relapse (CIR), and the secondary outcomes were progression-free survival (PFS), overall survival (OS), engraftment time, graft-versus-host disease (GVHD), and non-hematological adverse effects. Twenty-four R/R AML patients from the First Affiliated Hospital of Xi’an Jiaotong University were enrolled, and all achieved engraftment. Mucositis was the predominant toxicity and was managed appropriately. The two-year CIR was 10%. The two-year OS and PFS were 78.9 ± 11.1% and 51.2 ± 19.3%, respectively. Two patients experienced relapse, and three patients died of infection. Subgroup analyses demonstrated that maintenance treatment post-transplantation may improve OS. The MTBF regimen for salvage allo-HSCT in R/R AML exhibited notable anti-leukemia activity and tolerable toxicity. (NCT06385808, Efficacy and Safety of MTBF Conditioning Regimen for Salvageable Allo-HSCT in the Treatment of R/R AML).

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Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a major therapeutic challenge after allogeneic hematopoietic stem cell transplantation. Although ruxolitinib and basiliximab are widely used, their limitations highlight the need for safer, more effective, and scalable biologic strategies. Xenopax, a humanized anti-CD25 monoclonal antibody, has demonstrated encouraging results across real-world and clinical studies. The multicenter RELAX study reported a 28-day overall response rate of 64.5% and a 2-year overall survival of 68.0%, with reduced corticosteroid exposure and infection rates compared with historical basiliximab cohorts. Importantly, RELAX incorporated an economic assessment, showing a lower incremental cost per responder and reinforcing xenopax as a cost-efficient option for SR-aGVHD. Beyond salvage therapy, xenopax is gaining momentum in prophylactic settings, including as a potential replacement for methotrexate in haploidentical transplantation. Looking ahead, integration with autonomous decision-support systems—most notably daGOAT, the first AI platform validated to prescribe risk-adapted GVHD prophylaxis—may further strengthen CD25-targeted approaches. Together, these developments position xenopax as a versatile biologic with the potential to reshape both treatment and prevention paradigms in GVHD management.

This retrospective study evaluated 75 patients with chronic active Epstein–Barr virus infection (CAEBV) to compare the efficacy and survival outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) and programmed death-1 (PD-1) blockade therapy. Patients were classified into HSCT and non-HSCT groups. The primary endpoints were overall response rate (ORR), overall survival (OS), and event-free survival (EFS). HSCT significantly improved ORR, 3-year OS, and 3-year EFS compared to non-HSCT treatment. Subgroup analysis showed that PD-1 blockade achieved outcomes comparable to HSCT in a subset of patients; however, HSCT remained superior, overall, particularly in patients without hemophagocytic lymphohistiocytosis (HLH). The presence of HLH was identified as an independent risk factor for inferior survival. In conclusion, allogeneic HSCT remains the preferred curative strategy for CAEBV, whereas PD-1 blockade represents a promising alternative for carefully selected patients. Early recognition and management of HLH are crucial for improving prognosis.

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Intramedullary cellular transplantation within the human spinal cord has historically been regarded as a highly experimental intervention associated with substantial theoretical risk. However, cumulative clinical evidence progressively challenges this perception. Multiple early-phase clinical studies have demonstrated the technical feasibility and procedural tolerability of intramedullary and intralesional cellular delivery in spinal cord injury (SCI), employing heterogeneous cellular products, including bone marrow-derived mononuclear cells, mesenchymal stromal cells (MSCs), and neural stem cells. Despite considerable heterogeneity in cellular composition, dosing strategies, injection volumes, and delivery paradigms, severe injection-related complications remain uncommon. Reported adverse events are predominantly mild and transient, while procedure-induced neurological deterioration has not emerged as a reproducible safety signal. These observations suggest that controlled spinal cellular administration may represent a biologically tolerated intervention rather than an intrinsically destabilizing procedure. Beyond procedural considerations, long-term biological safety remains a central dimension of translational evaluation. While theoretical concerns persist — particularly regarding tumorigenesis, clonal selection, and potential genomic instability associated with ex vivo MSC expansion — currently available clinical data have not identified reproducible or causally attributable neoplastic transformation signals within currently reported follow-up durations. Interpretation of long-term safety outcomes therefore requires careful distinction between theoretical biological plausibility and empirical clinical observations. In parallel, minimally manipulated autologous cellular products such as freshly isolated stromal vascular fraction (SVF) introduce a complementary translational framework. By preserving physiological cellular heterogeneity and eliminating risks associated with ex vivo expansion, SVF-based approaches further emphasize the need to reinterpret cellular variability as an intrinsic biological property rather than a marker of product instability. Collectively, available evidence supports consideration of multidimensional safety frameworks integrating procedural, short-term biological, and long-term theoretical domains. Future progress will depend on harmonized reporting standards, extended longitudinal evaluation, and large-scale collaborative datasets capable of refining biologically grounded safety models for spinal cellular therapies.

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The global shortage of human donor livers poses a formidable barrier to treating end-stage liver diseases and unresectable hepatic malignancies, leaving millions of patients without life-saving options each year. While genetically engineered pig-to-human xenotransplantation has achieved significant breakthroughs in cardiac and renal fields, liver xenotransplantation has long lagged due to the liver’s intricate metabolic, synthetic, and immunological functions. The recent report by Zhang et al. in the Journal of Hepatology—documenting the world’s first successful auxiliary liver xenotransplantation from a 10-gene-edited pig to a living human, with the recipient surviving 171 days—marks a transformative milestone in regenerative medicine. This commentary examines the study’s groundbreaking contributions to donor genetic engineering and perioperative clinical management, while critically analyzing the persistent challenge of xenotransplantation-associated thrombotic microangiopathy and outlining future directions to advance clinical translation.

The tumor microenvironment (TME) plays a significant role in the occurrence, development, and prognosis of lymphomas. The mechanisms of each TME component in lymphoma and related therapeutic strategies are reviewed in this article. In the immune-related TME, regulatory T-cells (Tregs), tumor-associated macrophages (TAMs), and other immune cells mediate immune suppression and evasion. In the non-immune-related TME, cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) are involved in tumor progression, drug resistance, and immune evasion. In addition, aberrant glucose, amino acid, and lipid metabolism in tumor cells not only sustain their rapid proliferation and survival but also reshape the TME to favor immune escape, thereby worsening patient outcomes. Various treatment strategies targeting the components of the TME and metabolic abnormalities have brought new hope for the treatment of lymphoma. Further in-depth investigation into the intricate crosstalk between the TME and lymphoma cells will be instrumental in developing more effective, personalized precision therapies to improve patient survival.

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Autologous chondrocyte implantation (ACI) has long been regarded as the gold-standard chondrocyte-based therapy for articular cartilage repair. The main challenge in ACI is that chondrocytes lose their chondrogenic phenotype after monolayer expansion in vitro. The monolayer-expanded chondrocytes show dedifferentiation and senescence, hindering their ability to synthesize hyaline cartilage. Currently, there is no effective method to alleviate dedifferentiation and senescence in these monolayer-expanded chondrocytes. Adipose-derived stem cells (ADSCs) have been increasingly explored as a viable alternative cell source to chondrocytes for articular cartilage tissue engineering. Besides inducing chondrogenesis of ADSCs into chondrocyte, recent research emphasizes the positive impact of ADSC-secreted extracellular vesicles (ADSC-EVs). We demonstrate that ADSC-EVs alleviate dedifferentiation and senescence in monolayer-expanded chondrocytes, enhancing their capacity to produce hyaline cartilage. The ADSC-EVs treatment redifferentiated the monolayer-expanded chondrocytes by upregulating collagen type II (Col-II), sulfated glycosaminoglycan (sGAG), and SOX-9 expression and decreasing collagen type I (Col-I) levels. The redifferentiated chondrocytes also showed enhanced cell proliferation and reduced levels of P16 and senescence-associated β-galactosidase (SA-β-gal). Moreover, ADSC-EV treatment increased the ability of monolayer-expanded chondrocytes to synthesize hyaline cartilaginous matrices in 3D pellet culture. This effect is achieved through the suppression of interleukin-1β–induced mitogen-activated protein kinase (MAPK) signaling. Through next-generation sequencing and bioinformatic analyses, the miRNAs contained in ADSC-EVs were revealed as key candidates involved in mitigating dedifferentiation and senescence. Our findings propose a novel approach employing ADSC-EVs to restore the chondrogenic phenotype of monolayer-expanded chondrocytes, offering an alternative strategy for more effective ACI.

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Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic liver disorder and can progress to steatohepatitis and fibrosis; although approved pharmacotherapies for metabolic dysfunction–associated steatohepatitis (MASH) with fibrosis remain limited. Autologous chemically induced liver progenitor (CLiP) cells, generated from mature hepatocytes without genetic modification, have shown therapeutic promise in rodents, but their efficacy has not been tested in large animals. Six female Clawn miniature pigs (15–42 kg) were fed a high-fat, high-cholesterol diet to induce MASLD with biopsy-proven fibrosis (Brunt stage ≥1). Animals were assigned to CLiP transplantation (n = 3) or saline control (n = 3). Autologous CLiPs (5 × 10⁷) were generated from laparoscopically resected liver wedges, expanded ex vivo, and infused intraportally. Safety was assessed by monitoring, liver function tests, and lipid profiles. Efficacy was evaluated 1 month later by blinded histology and immunohistochemistry. CLiP transplantation was feasible and well tolerated. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) showed minimal changes in both groups, but total cholesterol and triglycerides decreased in treated pigs and increased in controls. Histologically, two of three CLiP-treated livers regressed from Brunt stage 1 to 0, with resolution of steatosis and reduced stellate cell activation, whereas controls showed no regression. These findings support CLiP therapy as a regenerative option for MASLD.

Liver cirrhosis causes substantial morbidity, and options beyond transplantation are limited. Umbilical cord–derived mesenchymal stem cells (UC-MSCs) may support liver repair, but their delivery via the hepatic artery has not been evaluated. This study assessed the safety and exploratory efficacy of allogeneic UC-MSCs infusion in cirrhosis. Twenty patients with liver cirrhosis entered a single-center open-label pilot trial in Hanoi, Vietnam, between 2020 and 2023; 17 completed follow-up and were included in exploratory analyses. All received a single hepatic artery infusion of UC-MSCs at 1 × 10⁶ cells/kg and were assessed at baseline, 3, 6, and 12 months for liver function, Model for End-stage Liver Disease (MELD) and Child–Pugh scores, Chronic Liver Disease Questionnaire (CLDQ), and adverse events. No serious adverse events occurred; mild events were self-limited. Albumin increased at 3 and 6 months (P = 0.048; P = 0.027). Bilirubin, liver enzymes, coagulation, and MELD remained stable. Child–Pugh score decreased transiently at 3 months (P = 0.024). CLDQ increased across most domains, except systemic symptoms. Hepatic artery infusion of UC-MSCs was safe and well tolerated, with observed increases in albumin and in most CLDQ domains, while other parameters remained stable. Findings are exploratory because of the small sample size and lack of a control group and therefore require confirmation in larger, controlled studies.

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Vascularized composite allotransplantation (VCA) enables functional and aesthetic reconstruction after complex tissue loss but remains limited by donor scarcity and immunosuppression. Xenotransplantation, using tissues from other species, offers a potential solution. While progress in solid organ xenografts has accelerated, vascularized composite xenotransplantation (VCX) remains largely experimental. This study presents the first systematic review of VCX, tracing its development over the past century and preclinical efforts to overcome immunologic and technical barriers. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines searched PubMed, EMBASE, Cochrane, Web of Science, and Google Scholar for English-language VCX studies. Methodological quality was assessed using the Newcastle-Ottawa Scale, SYRCLE Risk of Bias tool, and Oxford Levels of Evidence. Of 257 records, six preclinical studies (1885–2023) met inclusion criteria. Donor species included pigs, rabbits, dogs, and humans; recipients were rodents or nonhuman primates. Most used heterotopic grafts (e.g., limbs, groin flaps, thymosternal blocks) combining skin, muscle, bone, and nerves. Techniques included cryopreservation, microsurgical anastomosis, and genetically modified pig grafts (e.g., GalTKO.hCD46). All demonstrated short-term survival without long-term function. Despite technical feasibility, VCX remains experimental. Advances in gene editing, immune modulation, and tissue engineering are essential for clinical translation and may ultimately redefine reconstructive transplantation.

Cell transplantation using cell sheet technology is a promising regenerative approach that enables the delivery of a large number of viable cells while preserving cell–cell interactions and extracellular matrix. However, the clinical application of autologous cell sheets is limited by donor-site invasiveness, prolonged preparation time, and high manufacturing costs. Allogeneic cell sheets may overcome these limitations, but their therapeutic effects and immunological profiles require further clarification. In this study, we investigated the tissue-repair effects and immune responses associated with allogeneic skeletal muscle-derived cell (SMDC) sheet transplantation. In vitro analyses showed that human SMDCs suppressed activated T-cell proliferation in a cell number-dependent manner, lacked co-stimulatory molecules, and expressed immune checkpoint ligands, suggesting a potentially low-immunogenic and immunomodulatory phenotype. For in vivo evaluation, L8-derived syngeneic comparator sheets and allogeneic SMDC sheets derived from different rat strains were transplanted onto the serosal surface in a rat gastric ulcer model. SMDC sheet transplantation promoted early ulcer repair without increasing systemic inflammatory responses, as assessed by serum C-reactive protein levels. Histological analyses revealed limited macrophage and T-cell infiltration at the transplantation sites, although the extent of local immune responses varied depending on donor–recipient strain combinations. Transcriptomic analysis of ulcer tissues showed that the L8-derived syngeneic comparator and selected allogeneic groups shared downregulation of inflammation-related pathways, whereas another allogeneic donor strain induced a distinct transcriptional profile. These findings suggest that allogeneic SMDC sheets can promote early tissue repair without inducing overt systemic inflammatory activation. However, donor–recipient strain compatibility may influence local immunological and transcriptional responses after transplantation. The observed effects are consistent with early paracrine and immunomodulatory mechanisms, although direct cell tracking and more detailed immunological analyses are required. Allogeneic SMDC sheets may represent a potential ready-to-use strategy for gastrointestinal tissue repair, provided that appropriate donor selection and further preclinical validation are performed.

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Extracellular vesicles (Evs) act as a natural intercellular message transmitter, Evs can carry proteins, ribonucleic acid (RNA) and other bioactive substances, and have rich biological regulatory functions. Because of its low immunogenicity and high biocompatibility, it has become a popular research object in drug delivery. These remarkable properties also create new opportunities for modern therapy. However, due to the complex preparation process, there are challenges in terms of targeting accuracy, load release controllability, and pharmacokinetic optimization, and many problems may be encountered in reality. Based on real-life biomedical experiments, this paper summarizes the methods and types of Evs loading drugs, membrane modification methods, and the use of biological materials to improve the release efficiency, so as to provide reference for future research on engineered Evs.

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B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy has demonstrated promising efficacy in relapsed/refractory multiple myeloma (MM). However, evidence supporting its use in earlier treatment settings remains limited. This study presents a preliminary case series evaluating the feasibility of BCMA CAR-T cell therapy as post-induction consolidation in newly diagnosed multiple myeloma (NDMM) patients who did not proceed to autologous stem cell transplantation (ASCT). Four patients were included in this analysis. After induction therapy, all patients achieved very good partial response or better and did not proceed to ASCT due to ineligibility or personal preference. They subsequently received BCMA CAR-T cell therapy as consolidation treatment. All patients tolerated the BCMA CAR-T cell infusion well. Cytokine release syndrome occurred in all cases, but was limited to grades 1–2, and no immune effector cell–associated neurotoxicity syndrome was observed. Following therapy, patients maintained or further deepened responses and ultimately reached stringent complete response (sCR) and minimal residual disease (MRD) negativity. During a median follow-up period of 17.8 months, all patients remained in sCR status and MRD negativity without the need for additional anti-tumor therapy, and none experienced relapse or disease progression. These preliminary results suggest that BCMA CAR-T cell therapy as post-induction consolidation is feasible and associated with manageable toxicity in NDMM patients not proceeding to ASCT, warranting further evaluation in larger prospective studies.

Islet transplantation is a promising treatment for diabetes, but the shortage of donor islets limits its broad application. Induced pluripotent stem cells (iPSCs) provide an alternative source for generating insulin-producing cells; however, whether the somatic cell origin of human iPSCs influences pancreatic endocrine differentiation remains incompletely defined. In this study, we generated iPSCs from human pancreatic duct cells (HD-iPSCs) and compared their differentiation propensity and functional characteristics with human fibroblast-derived iPSCs (HF-iPSCs) under identical differentiation conditions. HD-iPSC-derived cells showed higher expression of pancreatic endocrine and β-cell-associated markers, including insulin, PDX1, and FOXA2, compared with HF-iPSC-derived cells. Flow cytometric analysis further confirmed a higher proportion of insulin-positive cells in differentiated HD-iPSC-derived cells. Functionally, HD-iPSC-derived cells exhibited greater glucose-stimulated C-peptide secretion than HF-iPSC-derived cells, although their secretory capacity remained lower than that of native human islets. Following transplantation into streptozotocin-induced diabetic mice, HD-iPSC-derived cells reduced blood glucose levels more effectively than HF-iPSC-derived cells, and insulin-positive grafts were detected in vivo. These findings suggest that human pancreatic duct cell-derived iPSCs have enhanced pancreatic endocrine differentiation potential compared with fibroblast-derived iPSCs. Although further maturation and optimization are required, pancreatic duct cells may represent a favorable somatic cell source for generating iPSC-derived insulin-producing cells for diabetes cell therapy.

Craniomaxillofacial (CMF) bone defects pose significant regenerative challenges due to complex anatomy and physiological demands. While autologous bone grafting remains the gold standard, it is limited by donor-site morbidity and supply constraints. Mesoporous bioactive glass (MBG), characterized by its ordered nanoporous structure and superior bioactivity, offers a promising alternative. This review systematically analyzes the integration of MBG with 3D printing technologies, including direct ink writing, stereolithography, selective laser sintering, and fused deposition modeling. We critically evaluate physicochemical challenges such as rheological optimization and thermal devitrification while elucidating the “osteo-immune-vascular” axis orchestrated by these scaffolds. Specifically, we discuss how ionic dissolution products modulate macrophage polarization, stabilize hypoxia-inducible factor-1α (HIF-1α) to induce CD31ʰⁱEmcnʰⁱ vessel formation, and activate Wnt/β-catenin signaling. Despite promising preclinical data, clinical translation faces hurdles regarding regulatory approval and manufacturing standardization. Future developments in 4D printing, AI-driven inverse topology design, and organ-on-a-chip validation represent a paradigm shift from passive substitution to active regeneration, paving the way for the tissue-engineered reconstruction of complex CMF defects.

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Chronic active Epstein–Barr virus (CAEBV) infection is a rare and highly lethal lymphoproliferative disorder. The pathological basis of this condition involves Epstein–Barr virus (EBV) persisting in hematopoietic stem cells, driving clonal expansion of T cells or natural killer (NK) cells, and subsequently triggering systemic inflammatory responses and multi-organ failure. Current treatment modalities, encompassing antiviral medications, immunosuppressants, and cytotoxic chemotherapy, offer only transient remissions, with the majority of patients ultimately experiencing relapse. Recent single-cell sequencing and chimera studies have confirmed that EBV-infected hematopoietic stem cells constitute the “seed” cell population for CAEBV initiation and maintenance. This finding indicates that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment known to date that can fully eradicate viral reservoirs and restore normal immunity, suggesting that it may represent a curative strategy. Nevertheless, transplantation timing, donor matching, conditioning intensity, and transplant-related complications have been shown to have a significant impact on long-term prognosis. The clinical decision-making process necessitates a high degree of individualization, incorporating molecular risk factors, disease activity, and comorbidities. Advancing research into the latent-lytic cycle regulation mechanisms of EBV, in addition to the clinical translation of small-molecule inhibitors targeting viral proteins and EBV-specific adoptive cell therapies, holds great promise for the future. One such potential avenue for future research is the development of an integrated “pre-transplant viral load reduction-post-transplant relapse prevention” strategy. This approach shows great potential in reducing transplant-related mortality and continuously improving survival outcomes for CAEBV patients.

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Recent years have witnessed rapid advancements in 3D bioprinting and the widespread application of mesenchymal stem cells (MSCs) across various medical disciplines. The synergistic integration of 3D bioprinting and MSCs has opened innovative avenues for tissue engineering and regenerative medicine, particularly in bone tissue repair and regeneration. However, the progress of 3D bioprinting in the field of MSCs research still requires further exploration, and there remains a scarcity of related bibliometric analyses in this domain. With the aim of addressing this existing gap, this research systematically searched the Web of Science Core Collection for publications spanning from January 2003 to October 2025. It employed CiteSpace for cluster and evolution analysis, VOSviewer for collaboration network and keyword co-occurrence analysis, and the R package “bibliometrix” for statistical evaluation of bibliometric indicators. This bibliometric analysis focused on tissue engineering research integrating 3D bioprinting with MSCs, encompassing 1,846 original articles. These articles were authored by 10,276 researchers from 2,024 institutions across 69 countries and published in 342 academic journals. From 2014 to 2023, the number of annual publications exhibited a fluctuating yet rapid upward trend. China and the United States emerged as the most influential countries, with China experiencing a particularly substantial increase in research output—though international collaborations among institutions and authors remained limited. Wu C.T. and Bose S. stood out as key contributors to this field, while journals such as Biomaterials and Biofabrication have significantly advanced the discipline. High-frequency keywords including “3D printing” and “tissue engineering” reflected the core research directions, whereas emerging terms such as “MSC-EVs” and “nanocomposites” indicated current frontiers; in addition, “bioink,” “3D scaffold,” “osteogenesis,” and “angiogenesis” represented areas gaining growing research attention. Overall, this bibliometric study provides a thorough overview of the research tendencies and developments related to 3D bioprinting in the MSC field.

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Although post-transplant cyclophosphamide (PTCy) is widely used to prevent graft-versus-host disease (GVHD), its protective effect remains inadequate in patients undergoing myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). We retrospectively evaluated the efficacy of PTCy combined with either pre-transplant or post-transplant antithymocyte globulin (ATG) for GVHD prevention in 114 haplo-PBSCT recipients. The PTCy+FTATG group (n = 74) received ATG at a total dose of 5 mg/kg on days −3 to −1, together with PTCy at 25 mg/kg on days +3 and +4. The PTCy+PTATG group (n = 40) received PTCy at 50 mg/kg on days +3 and +4, followed by ATG at 2.5 mg/kg on day +8. Both univariate and multivariate analyses showed that PTCy+FTATG prophylaxis significantly lowered the risk of grade II–IV acute GVHD (9.5% vs 27.5% [HR 0.24; 95% CI: 0.10–0.59; P = 0.002]) and grade III–IV acute GVHD (5.4% vs 17.5% [HR 0.19; 95% CI: 0.07–0.54; P = 0.002]). The 2-year cumulative incidence of chronic GVHD was 16.7% in the PTCy+FTATG group and 27.5% in the PTCy+PTATG group (P = 0.15). At 2 years, overall survival (OS), progression-free survival (PFS), and graft-versus-host disease-free relapse-free survival (GRFS) were 87.8% vs 72.5% (P = 0.04), 82.2% vs 65.0% (P = 0.03), and 78.1% vs 55.0% (P = 0.005), respectively. These results suggest that half-dose PTCy combined with low-dose pre-transplant ATG may be a promising strategy for GVHD prophylaxis.

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Knee osteoarthritis (OA) causes pain and disability, and autologous adipose-derived stem cell (ASC) therapy has emerged as a regenerative treatment option. This retrospective cohort study compared short-term outcomes of intra-articular ASC injections between patients with moderate (Kellgren–Lawrence [KL] 2/3) and severe (KL 4) OA. Among 242 treated patients, 98 in each group were analyzed after propensity score matching for age, sex, and body mass index. Pain (VAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales were evaluated at baseline and 1, 3, and 6 months. Both groups showed significant improvements in pain and function, with KL 2/3 patients exhibiting greater gains in KOOS Total, Activities of Daily Living, Sports/Recreation, Quality of Life, and VAS pain compared with KL 4. KOOS pain and symptoms improved similarly in both groups. Analgesic effects increased over time, and no serious adverse events were observed. Mild transient swelling or discomfort occurred in about 5% to 6% of cases. ASC injections provided meaningful symptom relief and functional improvement, particularly in moderate OA, suggesting that preserved joint structure benefits therapeutic efficacy. In advanced OA, benefits were present but attenuated, indicating limited regenerative potential in end-stage disease.

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To address the lack of effective treatments for germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH), a devastating condition in preterm infants with poor prognosis, this study investigated the neuroprotective potential and underlying mechanism of human umbilical cord-derived mesenchymal stem cells (HUCMSCs). Using a collagenase VII-S-induced GMH neonatal rat model and lipopolysaccharide-stimulated BV2 microglial cells, in vivo and in vitro experiments were performed. In vivo results showed that intraventricular HUCMSCs administration alleviated cerebral injury (reduced ventricular enlargement and cortical damage) and improved motor, memory, and cognitive functions in GMH rats. Both HUCMSCs and MSC-conditioned medium (MSC-CM) modulated microglial polarization toward the pro-resolving phenotype, suppressed pro-inflammatory polarization, and decreased TNF-α and IL-6 expression. Mechanistically, MSCs downregulated ROCK2 protein levels; the ROCK agonist PA abrogated MSC-CM’s anti-inflammatory effects, while the ROCK inhibitor Y27632 mimicked MSC-CM’s pro-M2 polarization. Collectively, this study demonstrates that HUCMSCs exert neuroprotection against GMH by suppressing ROCK2 to regulate microglial polarization, thereby mitigating neuroinflammation and promoting nerve repair, highlighting MSCs as a promising therapeutic strategy for GMH-IVH.

Hematopoietic stem cell transplantation (HSCT) is frequently accompanied by severe inflammation-related complications, among which graft-versus-host disease (GVHD) stands out as one of the most common and life-threatening. As a systemic inflammatory disorder, GVHD arises when donor T cells recognize the recipient’s alloantigens and initiate an immune attack. Currently, effective second-line treatment options remain scarce for patients with antibiotic-resistant or steroid-refractory GVHD. Mesenchymal stem cells (MSCs) are non-hematopoietic cells widely distributed in fetal and adult tissues and organs, endowed with multipotent differentiation potential and prominent immunomodulatory properties. Emerging evidence suggests that impaired function or apoptosis of MSCs exacerbates HSCT-associated complications and significantly compromises hematopoietic stem cell engraftment. Over the past two decades, leveraging their potent anti-inflammatory and immunomodulatory capacities, MSCs have been rapidly integrated into HSCT research and clinical practice, where they play a pivotal role in promoting hematopoietic engraftment and preventing or treating GVHD. This review elaborates on the molecular basis of MSCs’ anti-inflammatory effects and the inflammatory pathological characteristics of HSCT-related complications. We conducted a systematic literature search in PubMed, Web of Science, and Embase databases up to December 2025. The search strategy combined the following terms: (“mesenchymal stem cells” OR “MSCs”) AND (“hematopoietic stem cell transplantation” OR “HSCT”) AND (“graft-versus-host disease” OR “GVHD”) AND (“inflammation” OR “immune regulation”). It systematically analyzes the molecular mechanisms underlying MSCs’ anti-inflammatory actions and their application progress in HSCT, aiming to provide a theoretical foundation and translational insights for the rational clinical application of MSCs in HSCT.

Very small embryonic-like stem cells (VSELs) have been identified as potential precursors of the endothelial lineage in humans. Traditionally characterized by CD34 and CD133 markers, these populations remain poorly delineated, particularly regarding their morphological traits. Leveraging recent advances in imaging flow cytometry (iFC), this study sought to refine the characterization of VSELs by analyzing CD34⁺ and CD133⁺ Lin^⁻ CD45^⁻ cells from various sources, including bone marrow (BM), mobilized blood (MB), peripheral blood (PB), and cord blood (CB). Using high-resolution iFC, we assessed cell circularity and size, identifying significant morphological differences within subpopulations smaller than 7 µm. CD133⁺ cells predominantly exhibited irregular shapes, whereas CD34⁺ cells, regardless of CD133 co-expression, were mostly circular. Quantification across multiple sources revealed an enrichment of small circular CD34⁺ cells, especially in BM, MB, and CB. A comparative analysis with conventional flow cytometry (cFC) showed similar counts for CD34⁺ cells between methods (P = 0.06) but a significantly higher number of CD133⁺ cells with cFC (P < 0.0001), reflecting its inability to assess morphology. These findings highlight iFC as a powerful tool for rare stem cell analysis and propose CD34, rather than CD133, as a more reliable marker for identifying circular VSELs under 7 µm, refining future stem cell–isolation strategies.

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Donor-derived recipient-specific anti-HLA antibodies (RSAs) are rarely investigated in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective study, 185 haploidentical donor-recipient pairs were consecutively analyzed. Anti-HLA antibodies were detected in eight donors (4.3%) and 31 recipients (16.8%), with only one donor (0.5%) harboring RSAs. Donors were predominantly young, male, and transfusion-naïve, which likely contributed to the low antibody prevalence. No association was observed between donor antibody positivity and graft rejection or severe acute graft-versus-host disease (GVHD). However, recipients of antibody-positive grafts showed higher rates of Epstein–Barr virus (EBV) reactivation and transfusion refractoriness. Our findings suggest that donor-derived HLA antibodies, particularly RSAs, are infrequent and clinically limited under current haploidentical donor selection and immunosuppressive strategies, but may subtly influence post-transplant immune recovery.

Focal segmental glomerulosclerosis (FSGS) is one of the major causes of nephrotic syndrome, which can progress to end-stage renal disease, leading to kidney transplantation. Following renal transplantation, recurrence of FSGS (rFSGS) occurs in 30%–40% of patients with a high risk of graft loss. rFSGS typically presents with nephrotic-range proteinuria within days after post-transplantation. This review summarizes pathophysiology, biomarkers, and therapeutic strategies for rFSGS. Monogenic causes of FSGS, such as those caused by APOL1 mutation, show variable recurrence, while NPHS2 and ACTN4 show low recurrence of FSGS. Evidence suggests that idiopathic or primary FSGS is strongly associated with rFSGS, owing to podocyte structural damage caused by circulating permeability factors or immune dysfunction. Recent advances have identified biomarkers such as anti-nephrin antibodies, anti-CD40 antibodies, soluble tumor necrosis factor receptor 2 (sTNFR2), and soluble urokinase-type plasminogen activator receptor (suPAR) that help in early detection of recurrent FSGS. Post-transplant monitoring includes measuring urine protein-to-creatinine ratio (UPCR) and 24-h urine protein excretion, and a kidney biopsy. Preventive strategies, although including plasmapheresis and rituximab, show limited benefit and are not recommended for routine prophylaxis. Treatment options include plasmapheresis, immunoadsorption, and immunosuppressive drugs such as cyclophosphamide, rituximab, or calcineurin inhibitors. Recurrent FSGS is a clinical challenge with its multifactorial pathogenesis. Incorporating strategies such as genetic testing, risk stratification, and early detection with the help of biomarkers and early treatment can induce remission and preserve graft survival. Despite these advances, large prospective studies are still required for standardizing prevention and management strategies for rFSGS.

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Recent years have witnessed rapid progress in mitochondrial transplantation (MT) as a novel strategy for restoring mitochondrial function in diverse pathological conditions, including somatic mitochondrial transfer and reproductive mitochondrial replacement therapy. With its expanding applications in regenerative medicine and disease modeling, systematic quantitative evaluation of the global MT research landscape remains limited. To address this gap, we performed a bibliometric analysis of publications indexed in the Web of Science Core Collection from 1996 to 2024, with cross-database validation using Scopus. CiteSpace, VOSviewer, and the R package bibliometrix were applied to assess publication trends, collaboration networks, co-citation patterns, and keyword co-occurrence. In total, 1104 articles and reviews were included. The results revealed rapid growth in MT-related research, with the United States and China as leading contributors. Mitochondrion emerged as the most influential journal, while Yamada Y, Harashima H, and McCully JD were recognized as key authors. High-frequency keywords highlighted major themes including mitochondrial transfer, mesenchymal stem cells, and ischemia–reperfusion injury. Emerging terms such as extracellular vesicles, tunneling nanotubes, and advanced delivery systems, particularly the MITO-Porter platform, reflected current research frontiers. Overall, this study provides a comprehensive overview of global research trends and evolving directions in mitochondrial transplantation.

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Bone defects arise from trauma, infection, tumor resection, or congenital deformities, with large defects often progressing to nonunion. Autologous bone grafting is considered the gold standard therapy due to its osteoconductive, osteoinductive, and osteogenic properties, but it is limited by insufficient graft volume and donor-site complications. Allogeneic grafts and early synthetic bone substitutes partially addressed these limitations but typically provided only osteoconductive function and performed poorly in complex microenvironments. Bone tissue engineering utilizes bioactive scaffolds, cells, and factors to promote bone repair through mechanical support, osteogenic regulation, and cellular adhesion/proliferation/differentiation mechanisms. This review synthesizes current evidence on bioactive scaffold materials and bone marrow enrichment strategies for bone defect repair within a scaffold–bone marrow coupling framework. It also highlights key roles of pore architecture, angiogenesis, osteoimmunomodulation, and defect-specific material selection, while critically discussing current limitations, evidence gaps, and future translational directions.

This review examines how mechanical and chemical stimuli shape stem-cell behavior and how live-cell imaging combined with artificial intelligence can support the evaluation and optimization of 3D bioprinting workflows. Current evidence indicates that substrate stiffness, stretch, shear stress, compression, and soluble factors such as transforming growth factor beta (TGF-β), bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2) influence viability, migration, morphology, and lineage commitment in biopolymeric constructs. Imaging modalities including phase-contrast, fluorescence, confocal, two-photon, and light-sheet microscopy enable dynamic observation of these responses, while computational pipelines for segmentation, tracking, and feature extraction improve scalability and reproducibility of analysis. Across the reviewed studies, image-derived readouts such as cell distribution, motility, adhesion patterns, and early morphological changes emerge as promising indicators of construct quality and maturation potential. At the same time, broader application remains limited by phototoxicity, imaging depth constraints, data-processing demands, incomplete standardization of metrics, and restricted model generalizability. Overall, imaging-based cell tracking integrated with AI-assisted analysis offers a practical framework for post-print evaluation and iterative optimization in 3D bioprinting, with potential to strengthen quality control, reproducibility, and biological interpretation in regenerative engineering.

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Chimeric antigen receptor T-cell (CAR-T) therapy is a breakthrough in cancer treatment that can induce durable remission in patients with hematological malignancies who have failed prior therapies. As the use of CAR-T cell therapy increases, treatment-related renal complications deserves careful attention, particularly in patients with a solitary kidney, in whom renal complications may further increase clinical risk. Here, we report the case of a living kidney donor who was diagnosed with diffuse large B-cell lymphoma (DLBCL). After CAR-T cell therapy, the patient developed only mild cytokine release syndrome (CRS), without signs of acute kidney injury or renal impairment, and subsequently achieved a favorable metabolic response approaching complete remission.

Human pancreatic islets are essential for studies in β-cell biology, cell transplantation, and tissue engineering, yet access to viable human islets remains limited because conventional isolation protocols primarily rely on whole pancreases from deceased donors. Surgical pancreatectomy specimens may represent an accessible alternative source, but factors influencing successful isolation and functional preservation remain poorly defined. In this study, we evaluated a standardized method for isolating human islets from pancreatic tissue obtained from surgical pancreatectomy specimens and investigated patient-, specimen-, and surgery-related factors affecting islet yield and functionality. Between March and October 2024, 50 consecutive islet isolations were performed from pancreatic specimens obtained during surgical resections. Following enzymatic digestion, tissue fractions were cultured for 24 h before handpicking of morphologically intact islets. Islet yield was quantified as islet equivalents (IEQ), and functional integrity was assessed by glucose-stimulated insulin secretion assays on culture days 1, 3, and 5. A mean yield of 6690 IEQ/g pancreatic tissue was obtained (range 0–56,500 IEQ/g). Exploratory analyses suggested potential associations between islet yield and factors such as younger patient age, shorter surgical duration, and preserved pancreatic parenchyma. However, these findings should be interpreted cautiously given the variability of the specimens and the exploratory design of the study. These findings support the feasibility of using surgical pancreatectomy specimens as an accessible source of functional human islets for experimental and translational research.

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Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic beta cells (β-cell), leading to lifelong dependence on exogenous insulin. Despite advances in insulin delivery systems and glucose monitoring, achieving tight glycemic control remains a challenge for many patients. In recent years, stem cell–derived β-cell therapy has emerged as a promising strategy for restoring endogenous insulin production. This review explores the progress in differentiating human pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells (iPSCs), into functional insulin-secreting β-like cells. We highlight recent breakthroughs in improving cell maturity, graft survival, and immune protection. Delivery approaches, encapsulation technologies, and transplantation strategies are discussed alongside an overview of ongoing clinical trials. The review also addresses current limitations, including immune rejection, cell dedifferentiation, and safety concerns. Finally, we examine future directions, such as genome editing, personalized cell therapy, and the integration of artificial intelligence in monitoring and optimizing treatment. Stem cell–derived β-cell therapy holds transformative potential as a curative approach for T1D, but further research is essential to overcome remaining barriers to its widespread clinical application.

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Stem Cell–Derived β-Cell Replacement Therapy for Type 1 Diabetes: From Differentiation to Clinical Translation.

This graphical abstract summarizes how stem cell–derived β-cells are generated, protected from immune rejection, and translated into clinical therapies for type 1 diabetes. It highlights the convergence of stem cell biology, bioengineering, immunomodulation, and clinical trials, outlining a roadmap toward durable and potentially curative β-cell replacement.

Following biomaterial implantation, modulation of the acute immune response is essential for tissue regeneration. Polymorphonuclear leukocytes (PMNs) are critical effector cells in wound healing, and PMN dysfunction is mediated by mitochondrial dysfunction and can lead to prolonged inflammation and tissue damage. It was hypothesized that mitochondrial transplantation could be applied to PMNs in pro-inflammatory states as a means of upregulating regenerative proteins. Primary human PMNs were isolated from donor blood. Isolated PMNs and exogenous mitochondria were co-incubated to induce mitochondrial transplantation. Resulting interactions were assessed through microscopy to confirm initial uptake and mitochondria membrane potential retention, intracellular reactive oxygen species (ROS) analyses (n = 5), and PMN secretome quantification (n = 10) using multiplex protein analysis. Human PMNs were able to successfully uptake delivered mitochondria, and regenerative factors essential for tissue repair and immune cell recruitment including fibroblast growth factor-2 (FGF-2), interleukin (IL)-22, monocyte chemoattractant protein-1 (MCP-1), and granulocyte colony-stimulating factor (G-CSF) were significantly upregulated, indicating that exogenous mitochondria represent promising modulators of PMN function with broad clinical potential.

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Normal wound healing is a complex, yet critical process. Unfortunately, delayed or impaired wound healing presents a significant burden for numerous patients worldwide. Recent research has demonstrated that exosomes, a subtype of extracellular vesicles, may play a pivotal role in mediating cell-cell communication during wound healing. This narrative review aims to explore the use of exosomes in wound healing, with a focus on in vivo application of exosomes in animal wound models. A total of 73 studies are outlined in this narrative review, exploring either excisional, diabetic, burn, ischemic, or pressure wounds. Overall, the most frequent source of exosomes was adipose-derived mesenchymal stem cells, and the most common application method was local or subcutaneous injection. While these studies demonstrated great promise for the use of exosomes for therapeutic use in wound healing, this review also discusses the challenges and obstacles that will need to be overcome, including standardizing methods, further characterizing exosomes and identifying the optimal sources and doses in the development of exosome therapies.

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Autoimmune disease–related critical limb ischemia (AD-CLI) represents a significant portion of no-option critical limb ischemia (NO-CLI). Despite the demonstrated safety and efficacy of cell transplantation for NO-CLI, most studies focused on thromboangiitis obliterans (TAO). There remains a scarcity of reports on cell transplantation for AD-CLI induced by systemic lupus erythematosus (SLE), hypereosinophilic syndrome (HES), and so on. From May 2011 to May 2024, 22 patients with 36 ischemic limbs were enrolled. The primary outcome was amputation, whereas secondary outcomes included toe-brachial index (TBI), Wong-Baker Faces Pain Rating Scale (WBFPS), transcutaneous oxygen pressure (TcPO₂), and so on. Among them, 8 had SLE, 11 had HES, and 3 had eosinophilic granulomatous polyangiitis (EGPA). During the follow-up, one EGPA patient died, two patients underwent major amputation, and five underwent minor amputation. The 2-year major and total amputation-free survival rates were 86.4% and 72.7%, respectively. Critical limb ischemia (CLI) relief was observed in 14 patients, with a 1-year cumulative CLI-free survival rate of 61.0%. Significant improvements were noted in postoperative TBI and WBFPS. Autologous cell transplantation showed satisfactory safety and efficacy outcomes for non-TAO AD-CLI patients. Validation of the conclusions awaits more evidence based on the long-term outcomes of a larger number of patients.

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Cardiac xenotransplantation is advancing rapidly from basic research to early clinical use, but its research landscape has not been comprehensively mapped. We conducted a bibliometric and science-mapping analysis of English-language articles and reviews in the Web of Science Core Collection (1964–2025). Using VOSviewer, CiteSpace, and Bibliometrix, we assessed publication growth, collaboration networks, citation impact, and topic trends. The field has grown steadily and has accelerated in recent years in parallel with key clinical developments. Collaboration is strongest among institutions in the United States, Europe, and East Asia, and a small number of authors and centers contribute a large share of publications. Most studies are published in specialty transplantation journals, whereas major breakthroughs often appear in general medical journals. Research topics continue to focus on rejection and complement biology, while newer work highlights gene-edited donors, biosafety, clinical trial readiness, and pig-to-human models. Overall, the field appears to be maturing toward clinical implementation, and these findings can help guide research priorities, funding decisions, and policy planning.

To identify the optimal transplantation route for enhancing homing of mesenchymal stem cells (MSCs) to the kidney, thereby ameliorating rat Adriamycin nephropathy (AN). In vivo animal imaging revealed that ultrasound-guided intrarenal-arterial transplantation of GFP-MSCs markedly increased the number of MSCs homing to the kidney compared with the intravenous injection (IV) and renal parenchyma (RP) routes. Multimodal ultrasonography revealed that the renal artery (RA) group exhibited reduced renal parenchymal echogenicity and significantly increased cortical microvascular perfusion compared to the Adriamycin (ADR), IV, and RP groups. Hematoxylin and eosin (H&E) staining, Masson staining, and electron microscopy revealed that the RA group had an enlarged glomerular volume, diminished renal interstitial fibrosis, and attenuated mitochondrial damage compared to the ADR, IV, and RP groups. Western blotting, qRT-PCR and immunohistochemistry further indicated that the RA group mitigated rat AN by downregulating the JAK2, AKT1, and STAT3 signaling pathways more effectively than the ADR, IV, and RP groups did. The above findings indicate that under ultrasound guidance, MSCs transplanted via the renal artery can ameliorate AN-induced renal injury by acting on the JAK/STAT signaling pathway.

We used different approaches to transplant MSCs. Under ultrasound-mediated conditions, the MSCs transplanted via the renal artery significantly improved the renal damage in rats with doxorubicin-induced nephropathy through the JAK2/STAT3 signaling pathway.

The tumorigenesis and long-term bio-function of the implanted mesenchymal stromal cells (MSCs) were needed before clinical applications. We herein observed 7 months and investigated the viable tumors formation, the survival rate, the distribution of the injected cells in different reproductive organs after intravenous (IV) injection of the human menstrual blood–derived MSCs (LXT- and CDH-huMenSCs), and the human umbilical MSCs (huMSCs). The survival rate was not different among the huMenSCs, the huMSCs, and the negative control (IV injection of PBS) group. The longevities of the mice died within the observation period of the LXT and the huMSCs groups were significantly longer than that in the other groups; the positive control (IV injection of LLC (Lewis lung carcinoma cells)) group had the shortest longevity. The number of visible tumors in the huMenSCs, huMSCs, and the negative control group was lower than that in the positive control group. Human-sourced DNA was only detected in the ovaries of the huMSCs-injected mice. The histological morphology of the CDH- group had more normal follicles than that in other groups; the CDH- and the huMSCs group had more atretic follicles than that in other groups. In the huMenSCs and the huMSCs groups, the testis seminiferous tubules were fuller and more orderly arranged than the negative control group. The endometrial thickness of the LXT- group was thicker than that of the huMSCs- and the negative control groups, whereas the number of uterine glands was similar among all groups. The results suggested that IV administrations of xenogeneic huMenSCs and huMSCs in nude mice did not cause tumor formation. The injected huMenSCs from different donors functioned differentially on the mice’s life-span, endometrial thickness, and the number of follicles.

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Mesenchymal stem cells (MSCs) are recognized for their capacity to modulate immune responses, including those directed against tumors. In this study, we investigated the temporal effects of MSCs administration on anti-tumor immunity in a murine 4T1 breast cancer model. BALB/c mice were intraperitoneally injected with MSCs either 24 h (MSC1d) or 14 days (MSC14d) after orthotopic implantation of 4T1 mammary carcinoma cells. Early MSC administration (MSC1d) exhibited changes in immune cell phenotypes consistent with enhanced antitumor potential, including increased activity of natural killer (NK) cells, dendritic cells (DCs), macrophages, and T lymphocytes. These immunological changes correlated with reduced tumor growth and prolonged survival. Mice in the MSC1d group exhibited elevated serum levels of pro-inflammatory and anti-tumor cytokines (TNF-α, IFN-γ, IL-6, and IL-17), alongside decreased concentrations of immunosuppressive cytokines (TGF-β and IL-10). Tumor tissue analysis revealed increased infiltration of NK cells expressing markers associated with antitumor activity (IFN-γ-producing CD178⁺), CD80⁺/CD86⁺/I-A⁺ TNF-α-producing DCs, Th1-type CD4⁺ T cells, and Granzyme B-expressing CD8⁺ cytotoxic T lymphocytes (CTLs). Additionally, spleens of MSC1d-treated mice displayed significantly elevated populations of CD11c⁺ DCs, TNF-α/IFN-γ-secreting NK cells, CD4⁺ Th1 and Th17 cells, and CD8⁺ CTLs expressing markers associated with cytotoxic function (TNF-α, IFN-γ, and IL-17). Conversely, late MSCs administration (MSC14d) was associated with immunosuppression. Tumors from MSC14d-treated mice showed a decreased presence of IFN-γ⁺ and IL-17⁺ NK1.1⁺ cells, F4/80⁺ macrophages, IL-12⁺ DCs, and cytotoxic T cells. Spleens from these mice revealed a significant expansion of regulatory T cell (Treg)-like populations, including CD25⁻, FoxP3⁻, CD25⁺FoxP3⁻ cells, and TGF-β/IL-10-producing CD3⁺ and CD4⁺ T cells. Furthermore, serum levels of immunosuppressive mediators TGF-β and vascular endothelial growth factor (VEGF) were significantly elevated in the MSC14d group. Collectively, these findings demonstrate that the immunomodulatory effects of MSCs on breast cancer are highly dependent on the timing of their administration. Mesenchymal stem cells delivered during early tumor development enhance phenotypes consistent with antitumor potential and suppress tumor progression, whereas administration during later stages promotes immune evasion and tumor growth.

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This study investigated donor and islet isolation procedural factors influencing the islet yield during human islet isolation for transplantation. We retrospectively analyzed 133 islet isolations from deceased donors performed over 15 years at a single center. Isolations were stratified by post-purification islet yield (≥400,000 islet equivalents [IEQ], successful; <400,000 IEQ, unsuccessful) and by intent (clinical vs research). Higher donor body mass index and height over 170 cm were independently associated with successful isolation, whereas an enzyme perfusion temperature exceeding 14°C for ≥50% of the perfusion duration emerged as an independent risk factor for isolation failure. Clinically intended isolations exhibited tighter thermal control during Phase 1 digestion, greater digestion efficiency, and lower undigested tissue weight. A logistic regression model incorporating body surface area, packed tissue volume, and phase 1 digestion time (the interval from the start of warm recirculation to the collection phase) showed a moderate predictive value for isolation success (area under the curve = 0.755). Subgroup analysis revealed that longer relative phase 2 digestion time (the interval from the start of collection to its end) and higher North American Islet Donor Scores were associated with higher islet yield. These findings highlight the importance of donor anthropometrics, procedural consistency, and thermal regulation during islet isolation. Optimizing donor selection and controlling intra-procedural variables can improve islet yield and increase the likelihood of achieving the required clinical transplantation islet dose.

Facial nerve transection frequently results in incomplete functional recovery despite microsurgical repair due to axonal misalignment and limited intrinsic regenerative capacity. Schwann cells (SCs) are essential for peripheral nerve repair, supporting axon elongation, remyelination, and neurotrophic signaling. Human embryonic stem cell–derived Schwann cells (hESC-SCs), including Schwann cell precursors (SCPs) and immature SCs, constitute a scalable source of cells for tissue-engineered nerve grafts. This study investigated whether silicone conduits loaded with hESC-SCs could enhance facial nerve regeneration following complete transection in rats. hESCs were differentiated into SCPs or immature SCs using a stepwise in vitro protocol and purified by fluorescence-activated cell sorting (FACS). Forty-eight Sprague-Dawley rats underwent right facial nerve transection with a 3-mm gap and were randomly assigned to six groups: sham, axotomy only, empty conduit, Matrigel-filled conduit, conduit with SCPs, or conduit with immature SCs. At 12 weeks post-surgery, toluidine blue histochemistry, transmission electron microscopy (TEM), and morphometric evaluation demonstrated significantly larger axonal diameters, thicker myelin sheaths, and improved g-ratios in SC-treated conduits compared with empty conduit and axotomy-only controls (P < 0.05). Behavioral assessments showed partial functional recovery in SC-treated groups, with blink reflex performance significantly superior to controls at 8 and 12 weeks (P < 0.05). No significant differences were found between SCP and immature SC groups. These findings suggest that hESC-SCs incorporated into bioengineered conduits represent a potentially effective cell-based strategy for peripheral nerve regeneration. However, the interpretation of mechanistic effects is limited by the absence of direct engraftment validation and molecular analyses.

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Currently, there is very limited large-scale real-world data on the use of total marrow irradiation (TMI) as conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary objective of this study was to evaluate the real-world feasibility, efficacy, and safety of TMI-based conditioning in a large multicenter cohort. We retrospectively included consecutive patients undergoing allo-HSCT with TMI-based conditioning across four Chinese centers (2017–2024). The primary endpoint was overall survival (OS); secondary endpoints included disease-free survival (DFS), graft-versus-host disease–free/relapse-free survival (GRFS), nonrelapse mortality (NRM), graft-versus-host disease (GVHD), and safety. Among 205 patients, acute lymphoblastic leukemia (ALL) was the predominant diagnosis (81.5%). With a median follow-up of 19.3 months among survivors, 2-year OS, DFS, and GRFS were 71.7%, 60.0%, and 37.8%, respectively. One-year cumulative incidences of relapse and NRM were 20.2% and 13.8%. Day-100 grade II–IV acute GVHD occurred in 32.9%, and 1-year moderate-to-severe chronic GVHD in 19.1%. In multivariable analyses, acute myeloid leukemia (AML) diagnosis, haploidentical donor, and Eastern Cooperative Oncology Group (ECOG) performance status >1 were associated with inferior outcomes. Exploratory dose-stratified analyses were performed. Severe toxicities within 100 days were infrequent, predominantly infections (21.46%). In this large multicenter cohort, TMI-based conditioning demonstrated real-world feasibility with encouraging survival and manageable safety outcomes.

Tissue engineering strategies aim to create bone models to enhance our understanding of bone development and improve bone repair. Endochondral ossification (EO), where cartilage is replaced by bone, is difficult to replicate. We developed a collagen–hyaluronic acid (HA) hydrogel system for a three-dimensional (3D) co-cultivation of human chondrocytes, human mesenchymal stem cell (hMSCs), and human umbilical vein endothelial cells (HUVECs) to model the early stages of EO. To our knowledge, this specific tri-culture configuration within such a hydrogel composition has not been previously reported, providing a novel platform for studying EO-related cellular and matrix interactions in vitro. Differentiation and migration of hMSCs and HUVECs were studied in collagen I (Col I) hydrogels, with or without the addition of collagen II (Col II), HA, and chondrocytes. Col II and HA enhanced cell osteogenic differentiation, as documented by an increased COL1A1 and ALPL gene expression and enhanced alkaline phosphatase activity. Chondrocytes further promoted osteogenic cell differentiation and temporarily enhanced hypertrophic and angiogenic signaling as evidenced by elevated MMP13 and VEGFA expression. Furthermore, elevated SOX9 expression and Alcian blue staining indicated a chondrogenic-supportive environment. These findings highlight the synergistic effects of osteogenic and chondrogenic signals, emphasizing the potential of combining Col I and Col II, HA, and essential cell types in hydrogels to optimize bone and cartilage tissue engineering.

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This systematic review examines emerging delivery systems for bioactive molecules within regenerative endodontic therapy (RET) where hydrogels, nanogels, and polymeric nanoparticles along with advanced nanocarriers such as liposomes aquasomes, vesosomes, and mesoporous silica nanoparticles form the primary focus. The extensive literature search in PubMed, Scopus, and Web of Science databases (until August 2025) yielded a total of 47 eligible articles, including in vitro, ex vivo, animal, and a few clinical studies. Hydrogels emerged as a significant category, showcasing enhanced regenerative effects when used for the sustained release of various growth factors such as transforming growth factor-beta (TGF-β₁), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF). This was associated with improved angiogenesis and odontogenic differentiation. Nanogels exhibited high protein-loading efficiency and facilitated the differentiation of dental pulp stem cells, while polymeric nanoparticles demonstrated prolonged antibiotic and growth factor delivery with lower cytotoxicity. Among advanced nanocarriers, mesoporous silica nanoparticles showed promising potential for controlled release of growth factors and the formation of pulp-like tissues in animal models. In summary, the selected platforms for the delivery of bioactive molecules within RET show significant promise in terms of enhancing cell viability, bioactivity, and tissue regeneration. The findings indicate a practical pathway for clinicians aiming to achieve successful pulp–dentin tissue regeneration through translation research.

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NPM1-mutated acute myeloid leukemia (AML) is a distinct entity with specific biological and clinicopathological features. Prognosis varies depending on the associated mutations and clinical characteristics. This study evaluated the prognostic factors of NPM1-mutated AML in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We enrolled 139 patients with NPM1-mutated AML who underwent allo-HSCT. The median age at allo-HSCT was 47 years with a median follow-up of 1,134 days. The 3-year cumulative incidence of relapse (CIR), leukemia-free survival (LFS), and overall survival (OS) rates were 15.1%, 78.4%, and 78.0%, respectively. FLT3-ITD mutations showed higher CIR (22.6% vs 5.3%, P = 0.006), lower LFS (70.9% vs 88.1%, P = 0.019), and reduced OS (70.8% vs 87.5%, P = 0.036). FLT3-ITD and DTA mutations indicated adverse prognosis, while IDH1/2 mutations showed improved outcomes. Matched sibling donor (MSD) allo-HSCT patients had higher CIR and lower LFS and OS than unrelated donor (URD) or haploidentical-related donor (HRD) recipients. Pre-HSCT MRD status affected the outcomes, with MRD+ and nCR patients showing worse outcomes. Multivariable analysis identified FLT3-ITD, MSD, and pre-MRD status as significant predictors. In conclusion, FLT3-ITD and DTA mutations are associated with an adverse prognosis, whereas HRD or URD transplants may offer better outcomes than MSD allo-HSCT.

Ligament injuries can lead to lasting instability and early joint degeneration despite rehabilitation or surgery. Stem cell therapies may aid regeneration, but studies are highly variable. Bibliometric analysis can summarize trends, hotspots, and research gaps. We searched the Web of Science Core Collection for English-language original articles on stem cell therapy for ligament injuries from 2001 to 2025 on April 2, 2025, excluding non-original publications. Publication and citation trends were summarized, and co-authorship, co-citation, and keyword networks were mapped using Excel, VOSviewer, CiteSpace, and Bibliometric.com. A total of 599 articles were included, with steadily increasing annual publications. The United States and China were leading contributors, with strong collaboration networks involving major institutions such as the University of Pittsburgh and Zhejiang University. Keyword analyses identified seven main themes spanning mechanisms, clinical translation, tissue engineering, surgery/grafting, injury models, biomechanics, and biomaterials. Recent hotspots included “inflammation” and “artificial ligament”. Stem cell research for ligament injuries is increasingly focused on mechanisms and biomaterials, but evidence is still mainly preclinical and inconsistent. Better comparative clinical studies and standardized, well-defined biomaterial–cell approaches are needed.

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This study aimed to define the incidence of Clostridioides difficile infection (CDI), identify its risk factors, and evaluate its association with early post-transplant complications and overall clinical outcomes. To characterize CDI in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting, we retrospectively analyzed a cohort of 539 recipients who experienced diarrhea in the peri-transplant period (from conditioning to discharge from laminar flow). Among these diarrheic recipients, 64 patients developed CDI, the cumulative incidence of CDI was 12.1%, with a median onset of day -1 (range, -7 to +26) relative to HSCT. In a multivariate analysis, older age was independently associated with a lower risk of CDI (HR, 0.97; P = 0.008) among diarrheic recipients. The incidence of CDI stratified by the median onset time revealed that pre-transplant CDI was an independent risk factor for grade 1-4 lower gastrointestinal acute graft-versus-host disease (lower-GI aGVHD) (HR, 2.43; P=0.024). Furthermore, pre-transplant CDI was associated with a markedly increased risk of severe fungal infection (HR,6.97; P=0.026) and 100-day non-relapse mortality (NRM) (HR, 3.13; P=0.046). In conclusion, this study highlights a critical, timing-dependent distinction in CDI-associated severe complications and mortality in allo-HSCT recipients with diarrhea.

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Amniotic epithelial cells (AECs) have immunomodulatory and anti-inflammatory properties that may improve outcomes in cell transplantation. However, their effect on islet engraftment after intraportal co-transplantation remains unclear. We evaluated the impact of co-transplanting syngeneic 600 islet equivalents (IEQs) with human AECs (hAECs) via the portal vein in a rat streptozotocin-induced diabetes model. The co-transplantation (Co-Tx) group showed normalization of blood glucose levels within 7 days after transplantation, sustained normoglycemia thereafter, and achieved a higher diabetes reversal rate than controls (100% vs. 71.4%, p < 0.01). Serum CXCL1 levels were significantly lower in the Co-Tx group indicating suppression of early inflammatory responses. Thrombin-antithrombin complex (TAT) levels also tended to be lower, raising the possibility of attenuation of the instant blood-mediated inflammatory reaction (IBMIR). In contrast, no significant differences were observed in VEGF levels or intrahepatic microvascular density. Co-transplantation with hAECs enhances islet engraftment likely through suppression of early inflammation, highlighting their potential as an adjunctive cellular therapy in islet transplantation.

Peripheral nerve injury (PNI) often results in persistent functional deficits, and current treatments remain suboptimal. This study developed a tissue-engineered graft by integrating Cdc42-modified bone marrow-derived mesenchymal stem cell (BMSC)-derived exosomes (Exos-Cdc42) with an acellular nerve allograft (ANA) and evaluated its therapeutic potential for nerve regeneration and functional recovery. Exosomes were isolated from BMSCs, and Exos-Cdc42 were generated by transfecting these cells with Cdc42 overexpression vectors. In vitro, Exos-Cdc42 significantly enhanced Schwann cell proliferation, migration, and secretion of neurotrophic factor (BDNF, NGF, CNTF), while upregulating repair-associated markers and downregulating myelination-related markers. In vivo, the combination of Exos-Cdc42 and ANA improved functional recovery of the sciatic nerve, as evidenced by higher sciatic functional index scores and increased muscle weight. Histological analyses demonstrated enhanced axonal regeneration and myelination, characterized by thicker myelin sheaths and larger axon diameters. These findings suggest that Exos-Cdc42 enhance the therapeutic efficacy of ANA by promoting Schwann cell-mediated repair responses, representing a promising strategy for peripheral nerve regeneration.

Oral cancer ranks among the most prevalent malignant tumors of the head and neck, comprising 1%–2% of all global malignancies. Despite advancements in surgery, radiotherapy, chemotherapy, and immunotherapy, challenges remain in oral cancer treatment, including high recurrence rates, severe side effects, and limited efficacy. Hydrogels, biocompatible materials with a three-dimensional network structure, have emerged as promising candidates in oral cancer therapy due to their dual roles in drug delivery and immune modulation. This review examines the contribution of hydrogels to oral cancer treatment through their synergistic control of drug release and localized immune activation. By enabling targeted, stimuli-responsive drug release, and enhancing local immune responses, hydrogels reduce systemic toxicity and improve treatment precision. When integrated with advanced approaches such as gene therapy and immune modulation, hydrogels hold potential to further amplify therapeutic efficacy. Although preclinical results are promising, clinical translation requires addressing scalability, quality control, and long-term safety concerns. With ongoing development, hydrogels are positioned to become vital tools in the treatment of oral cancer, periodontitis, and other oral diseases.

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Umbilical cord mesenchymal stromal cells (UC-MSCs) are emerging as leading stem cells in regenerative medicine due to their high proliferative capacity, potent immunomodulatory effects, and non-invasive collection. However, the absence of standardized guidance on optimal passage number and tissue-specific characterization criteria limits clinical translation, raising concerns about variability in potency, genomic stability, and safety. This review synthesizes evidence on how in vitro passaging alters UC-MSC properties, including purity, proliferation, senescence, genomic integrity, differentiation, and immunomodulation. Preclinical data suggest that UC-MSCs tolerate extended passaging better than MSCs derived from other sources, with several functional attributes preserved up to later passages. Clinical evidence indicates that early to middle passages (P3–P5) achieve the best balance between scalability and therapeutic efficacy. We further propose an updated immunophenotypic framework incorporating tissue-specific positive and negative markers to enhance clinical-grade characterization. Establishing harmonized passage guidelines and potency assays is essential to maximize reproducibility, safety, and the translational potential of UC-MSC therapies.

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Traumatic brain injury (TBI) remains a major global health challenge with limited effective treatments. This systematic review documents the significant evolution of mesenchymal stem cell (MSC) therapies from traditional cell transplants to advanced cell-free products and engineered delivery systems. A systematic search was conducted across Web of Science, Embase, and PubMed/Medline for studies published from January 2015 to June 2025, resulting in the inclusion of 80 studies for qualitative synthesis. The review identifies four primary therapeutic mechanisms: reducing inflammation, protecting brain cells, maintaining the blood–brain barrier, and supporting tissue repair/regrowth. This PROSPERO-registered systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality and risk-of-bias were rigorously assessed using a multi-tool approach tailored to study design (Cochrane RoB, SYRCLE, NOS/JBI). Recent clinical evidence (e.g. STEMTRA trial) suggests these treatments are safe and can improve function in chronic TBI patients. Despite this, critical research gaps persist in establishing standardized protocols, optimal dosing, and long-term safety data. Emerging trends include (1) shifting toward enhanced exosomes/secretomes, (2) integrating MSCs/derivatives with advanced biomaterials for controlled delivery, (3) exploring alternative MSC sources, and (4) developing combination therapies. With a deepening mechanistic understanding and positive early clinical results, future research must prioritize standardization and personalized treatment plans to accelerate clinical translation.

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Neurodegenerative dementias, including Alzheimer’s disease and vascular dementia, have long been viewed through a neuron-centric lens. However, growing evidence highlights the indispensable and multifaceted roles of glial cells, astrocytes, microglia, and oligodendrocytes in both the onset and progression of these disorders. While prior reviews have cataloged glial dysfunction in isolation, this review offers a novel, integrative framework that maps the interconnected roles of glial subtypes across molecular, cellular, and circuit-level pathology in dementia. We critically synthesize recent advances in single-cell RNA sequencing, spatial transcriptomics, and glial imaging to redefine glial heterogeneity and function in disease states. Special emphasis is placed on the dynamic cross talk between glial populations and the feedback loops that govern their dual roles in neuroprotection and neurodegeneration. Furthermore, we examine emerging therapeutic strategies targeting glial-specific pathways, including NF-κB, JAK/STAT, CSF1R, and TREM2 signaling, as well as remyelinating agents and stem cell–based interventions. By integrating glial biology with therapeutic innovation, this review positions glial cells not as supporting actors but as central regulators and potential gatekeepers of dementia pathogenesis and treatment.

Post-transplant relapse remains the chief therapeutic challenge in Ph-negative B cell acute lymphoblastic leukemia (Ph^- B-ALL). This retrospective study evaluated whether short-course blinatumomab for measurable resident disease (MRD) eradication could improve transplant outcomes. We compared 23 patients receiving pre-transplant short-course blinatumomab (2-week) for MRD eradication with 46 chemotherapy-only controls. All achieved MRD-negative before allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Only two patients developed grade 2 cytokine release syndrome with blinatumomab. The neutrophil and platelet engraftment times were similar between the two groups. The blinatumomab cohort had a significantly lower 18-month cumulative incidence (CI) of relapse (p = 0.05) and chronic graft-versus-host disease (GVHD) (14.8% vs. 41.8%; p = 0.05), with comparable non-relapse mortality (NRM) (p = 0.98) and 180-day grade II-IV acute GVHD rates (p = 0.93). Consequently, this cohort showed superior 18-month relapse-free survival (RFS) (90.9% vs. 65.2%; HR 0.30, 95% CI 0.09-1.04; p = 0.04), improved 18-month overall survival (OS) (95.7% vs. 81.9%; HR 0.20, 95% CI 0.03-1.71), and a trend toward better GVHD-free and relapse-free survival (GRFS) (74.71% vs. 63.71%; HR 0.64, 95% CI 0.23-1.78). Multivariate analysis confirmed blinatumomab as an independent favorable factor for RFS. In conclusion, short-course blinatumomab as a bridge-to-transplantation could reduce the risk of relapse and improve survival for Ph^- B-ALL patients undergoing allo-PBSCT.

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Stromal vascular fraction (SVF)-based therapies and autologous fat grafting have emerged as promising regenerative strategies due to their pro-angiogenic, immunomodulatory, and trophic properties. However, despite encouraging preclinical and clinical findings, therapeutic outcomes remain highly heterogeneous, with marked variability in graft retention and functional efficacy between patients. Increasing evidence suggests that this variability cannot be explained solely by procedural factors or cellular composition, but may also depend on host-related immune and microenvironmental determinants. This review explores the biological mechanisms governing SVF engraftment and introduces the emerging concept of “SVF therapy resistance,” defined as the failure of autologous regenerative therapies resulting from maladaptive interactions between transplanted stromal cells and the host tissue environment. Particular attention is given to sterile inflammation, innate immune activation, and early graft–host interactions. Following transplantation, tissue injury and ischemia induce the release of danger-associated molecular patterns (DAMPs), triggering neutrophil recruitment, macrophage activation, complement signaling, and inflammatory remodeling. While controlled inflammatory responses may support tissue repair and angiogenesis, excessive neutrophil activation, neutrophil extracellular trap (NET) formation, persistent pro-inflammatory macrophage polarization, and impaired vascular adaptation may compromise graft survival and regenerative efficacy. The review further discusses how SVF processing, inflammatory priming, stromal cell heterogeneity, and donor-related factors—including obesity, aging, metabolic dysfunction, and chronic inflammation—may influence therapeutic responsiveness. Emerging evidence from mesenchymal stromal cell biology suggests that stromal cells are highly sensitive to inflammatory licensing and microenvironmental cues. Candidate biomarkers and immune profiling strategies capable of identifying responders and non-responders to SVF-based therapies are also reviewed. Finally, these mechanisms are discussed in spinal cord injury, a condition characterized by chronic inflammation and vascular dysfunction. Overall, this review proposes a translational framework linking innate immunity, sterile inflammation, angiogenesis, and stromal cell heterogeneity to the variability of SVF therapy outcomes, highlighting the need for personalized regenerative medicine approaches.

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Mesenchymal stromal cell (MSC)–based therapies have demonstrated broad therapeutic potential across inflammatory, degenerative, and neurological disorders; however, clinical outcomes remain highly variable, largely due to heterogeneity in cell source, dosing strategies, routes of administration, treatment timing, and patient-specific factors. This review evaluates how MSC dose and delivery route influence clinical efficacy and safety, and whether specific administration routes require tailored dosing strategies. A systematic literature search of PubMed, Scopus, Web of Science, and the Cochrane Library (2015–2025) identified 29 eligible clinical trials employing intravenous (n = 13), intrathecal (n = 10), intramuscular (n = 4), intranasal (n = 1), and multi-route (n = 1) administration, with doses ranging from 2 × 10⁵ cells/kg body weight to fixed doses exceeding 1 × 10⁸ cells. Intravenous delivery was predominantly used for systemic indications but was limited by pulmonary first-pass sequestration, whereas intrathecal and intranasal routes enhanced central nervous system targeting and intramuscular administration supported prolonged local persistence and paracrine activity. Although MSC therapy was generally well tolerated across studies, substantial outcome variability underscores the need for harmonized frameworks for dose selection, route optimization, and manufacturing consistency. This review highlights critical gaps in dose–route optimization and supports the development of standardized clinical guidelines and advanced strategies, including MSC priming and engineering, to improve therapeutic predictability and translational success.

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Organ-on-a-chip (OoC) platforms are microengineered systems that combine microfluidic control with living cells to emulate the physiological functions of human tissues and organs in vitro. OoC has become a transformative tool in pharmaceutical research, offering unprecedented capabilities for predicting drug efficacy, pharmacokinetics, and toxicity with human-relevant precision. This study presents a comprehensive scientometric and patent landscape analysis of OoC studies in pharmaceutical sciences spanning 2008–2025. Using CiteSpace, we mapped 1,786 publications to identify influential authors, landmark works, and temporal shifts in thematic focus. Keyword burst and clustering analyses reveal emerging frontiers in multi-organ integration, disease modeling, and drug screening. Patent data indicate a rapid expansion since 2016, led by China and the United States, underscoring a translational trajectory from fundamental research to applied biotechnology. These findings delineate the evolving intellectual and technological framework of organ-on-a-chip research in drug development and highlight future priorities in multi-organ systems, biomaterials optimization, and clinical translation.

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Metastatic colorectal cancers (mCRCs) exhibit substantial heterogeneity at the genetic, transcriptomic, histological, and microenvironmental levels, which contributes to therapeutic resistance and variable clinical outcomes. Patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) have emerged as powerful platforms for modeling this complex disease. PDOs faithfully recapitulate tumor architecture, molecular features, and heterogeneity, enabling high-throughput drug screening and personalized treatment response prediction. In addition, PDX models maintain tumor–stroma interactions in vivo and accurately reflect histological and pharmacological phenotypes, supporting studies on treatment response and resistance mechanisms. Recent advances indicate that these models capture intratumoral, intertumoral, and interpatient variability; reveal patterns and mechanisms of drug sensitivity heterogeneity; and can be used to predict chemotherapy efficacy. However, limitations remain for both model types. Innovations such as humanized PDX mouse models and immune‒organoid coculture systems are being developed to overcome these barriers. This review summarizes the latest progress in PDO and PDX applications in research on mCRC heterogeneity, highlights their role in dissecting tumor heterogeneity, and discusses future directions for integrating these models into precision oncology.