Cell Transplantation最新文献

{"title":"Tissue repair and donor-dependent immune responses after allogeneic skeletal muscle-derived cell sheet transplantation in a rat gastric ulcer model.","authors":"Yuta Kawaguchi, Moeka Nakayama, Kengo Kanetaka, Miki Higashi, Yasuhiro Maruya, Shinichiro Kobayashi, Masaki Matsumura, Takahiro Naka, Susumu Eguchi","doi":"10.1177/09636897261466845","DOIUrl":"10.1177/09636897261466845","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261466845"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human pancreatic duct cell-derived iPSCs show enhanced differentiation into insulin-producing cells.","authors":"Sung-Bin Lim, Moon-Kyu Lee","doi":"10.1177/09636897261469970","DOIUrl":"10.1177/09636897261469970","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261469970"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and clinical relevance of donor-derived recipient-specific anti-HLA antibodies in haploidentical hematopoietic stem cell transplantation: a retrospective study.","authors":"Xianbo Huang, Yanling Ren, Shasha Wang, Chen Mei, Yu Xu, Jie Jin, Hongyan Tong, Jiejing Qian","doi":"10.1177/09636897261417187","DOIUrl":"10.1177/09636897261417187","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261417187"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12852576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential therapeutics ingredients for dental pulp regeneration focusing on DPSCs and DPSC secretome with market projection.","authors":"Vinita Dsouza, Amrutha Hebbar, Shashi Rashmi Acharya, Raviraja N Seetharam, Kirthanashri S Vasanthan","doi":"10.1177/09636897251414002","DOIUrl":"https://doi.org/10.1177/09636897251414002","url":null,"abstract":"<p><p>Regeneration of dental pulp has surfaced as an exciting area of exploration in regenerative endodontics, as a result of progress in stem cell biology and their applications, along with biomaterials. Of the different cell populations studied, dental pulp stem cells (DPSCs) are recognized as possessing significant regenerative potential considering their multipotency, immunomodulatory properties and capacity to differentiate into odontoblast-like cells. Interest has also increased in alternative approaches, such as the DPSC-derived secretome, which serves as a bioactive consulting of molecules like cytokines, growth factors and extracellular vesicles, to initiate regenerative processes through paracrine signalling without the limitations of cell-based treatments. This review highlights the relative therapeutic potential of DPSCs secretome when integrated with three-dimensional scaffolds for the regeneration of the pulp-dentin complex. We discuss the biological mechanisms by which DPSCs secretome helps in regeneration assess the compatibility of scaffolds, and review advantages and limitations regarding their use based on efficacy, immunogenicity, storage and clinical use. Although DPSC scaffolds provide direct tissue reconstruction, secretome-enhanced scaffolds are clinically applicable as a cell-free, scalable and potentially safer method. A better understanding of the advantages and disadvantages of DPSC secretome-modified scaffolds will assist in the development of future and emerging translational opportunities for personalized, minimally invasive regenerative endodontic therapies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251414002"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of cell transplantation for ischemic stroke: A meta-analysis of randomized controlled trials.","authors":"Xue-Song Liang, Ying-Xuan Guo, Johannes Boltze, Shen Li","doi":"10.1177/09636897261480252","DOIUrl":"10.1177/09636897261480252","url":null,"abstract":"<p><p>Cell transplantation is a potential therapeutic strategy for ischemic stroke, but its clinical efficacy remains inconsistent. This meta-analysis evaluated functional outcomes at different follow-up time points, as well as neuroimaging and paracrine biomarkers. A systematic search of Embase, PubMed, Web of Science, and the Cochrane Library up to December 31, 2025 identified 21 randomized controlled trials involving 1,269 patients. The analysis showed that cell transplantation improved NIHSS at 6 and 12 months and final follow-up; mRS at 12 months and final follow-up; and BI at 3 and 6 months and final follow-up. Functional independence increased as measured by mRS scores at 0-1 and 0-2 at 12 months and by BI ≥90 or 95 at 3 and 12 months and final follow-up. MSCs improved NIHSS and BI, EPCs improved NIHSS and mRS, whereas MNCs showed no statistically significant effects. BBB-bypassing delivery demonstrated consistent efficacy. Transplantation within 10 days or after 90 days showed beneficial effects. Fugl-Meyer assessment scores and VEGF increased after cell transplantation, while infarct volume and DTI-FA showed no change. Cell transplantation induced functional benefits. Efficacy may depend on cell type, delivery strategy, and timing of transplantation, underscoring the critical influence of these variables on therapeutic outcomes.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261480252"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pilot phase IIa randomized, placebo-controlled, double-blind trial of intravenous human pluripotent adipose-derived stem cells (PASCs) in Parkinson's disease: The REPOSE study.","authors":"María Laura Gimeno, Gregorio Chazenbalk, Lisa Riggioni, Abby Ortega, Luis Miranda, Juan Antonio Valverde, José A Molina-Mora, Linette González Rojas, Pamela Vargas, Carlos Zuñiga, Luis Rosales, Freddy Henríquez","doi":"10.1177/09636897261492438","DOIUrl":"10.1177/09636897261492438","url":null,"abstract":"<p><p>Pluripotent adipose-derived stem cells (PASCs) are a non-tumorigenic, stress-enduring SSEA-3⁺ cell population sharing key biological markers with Muse cells while representing a phenotypically distinct population. This Phase IIa randomized, double-blind, placebo-controlled pilot trial evaluated the safety, feasibility, and exploratory clinical effects of intravenous PASCs in Parkinson's disease (PD). Forty participants with Hoehn and Yahr stages I-III PD were randomized 1:1 to receive three intravenous infusions of PASCs (25 million cells) or placebo at baseline, month 3, and month 6, with 12-month follow-up. All participants underwent a structured neurological rehabilitation program. The primary endpoint was safety (CTCAE v5.0). No treatment-related adverse events of any grade were observed across 60 infusions. One thromboembolic event in the PASC group was independently adjudicated as of uncertain relationship to the study intervention, and one death in the placebo group was adjudicated as unrelated. For each of the seven exploratory functional and quality-of-life endpoints, the global treatment-by-time interaction was tested and adjusted for multiplicity using the Benjamini-Hochberg procedure; no endpoint reached significance after control of the false discovery rate (all q > 0.05). Repeated intravenous PASC administration is safe and feasible in PD. Efficacy was not demonstrated in this pilot trial, and the exploratory findings are hypothesis-generating, supporting further investigation in adequately powered Phase IIb/III trials.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261492438"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning models using longitudinal laboratory data predict survival in allogeneic stem cell recipients.","authors":"Asif Adil, Aryan H Patel, Damon P Ho, Obaid Ur Rehman, Catharine Root, Stephanie N Hurwitz","doi":"10.1177/09636897261493864","DOIUrl":"10.1177/09636897261493864","url":null,"abstract":"<p><p>Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative therapy for hematologic malignancies and bone marrow failure syndromes, yet outcomes remain highly heterogeneous and existing prognostic tools rely predominantly on pre-transplant clinical characteristics. We retrospectively analyzed 500 consecutive patients who underwent allogeneic HSCT at a single academic center between 2019 and 2025. Clinical characteristics, transplant variables, comorbidities, medication exposures, and longitudinal laboratory parameters were evaluated for associations with overall survival. Machine learning models incorporating dynamic post-transplant laboratory parameters demonstrated high performance in predicting overall survival compared to existing risk stratification techniques. Among evaluated predictors, early hematologic recovery emerged as one of the strongest determinants of long-term outcome. Specifically, achievement of a platelet count ≥90,000/μL by day +30 was independently associated with superior overall survival. These findings demonstrate that dynamic post-transplant laboratory data provide clinically meaningful prognostic information beyond traditional pre-transplant risk factors. Integration of early hematologic recovery metrics into machine learning-based prediction models may enable more accurate identification of high-risk patients and support individualized surveillance and management strategies following allogeneic HSCT.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261493864"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles secreted by adipose-derived stem cells alleviate dedifferentiation and senescence in monolayer-expanded chondrocytes by suppressing interleukin-1β-induced MAPK signaling.","authors":"Shun-Cheng Wu, Ling-Hua Chang, Che-Wei Wu, Chung-Hwan Chen, Je-Ken Chang, Mei-Ling Ho","doi":"10.1177/09636897261440426","DOIUrl":"10.1177/09636897261440426","url":null,"abstract":"<p><p>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 <i>in vitro</i>. 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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261440426"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory effects of mesenchymal stem cells and their research progress in hematopoietic stem cell transplantation: A comprehensive review.","authors":"Changling Zhu, Shuai Ma, Wangfu Jiang, Li Xu, Na Ma","doi":"10.1177/09636897261440416","DOIUrl":"10.1177/09636897261440416","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261440416"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulating ROCK2 by human umbilical cord mesenchymal stem cells promotes pro-resolving microglial polarization and alleviates cerebral injury in germinal matrix hemorrhage.","authors":"Mengting Yang, Sha Wu, Jianwei Xu, Xiaoping Zhu, Maoqiong Chen","doi":"10.1177/09636897261443446","DOIUrl":"10.1177/09636897261443446","url":null,"abstract":"<p><p>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, <i>in vivo</i> and <i>in vitro</i> experiments were performed. <i>In vivo</i> 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 <i>TNF-α</i> and <i>IL-6</i> 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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261443446"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}