Cell Transplantation最新文献

{"title":"Chronic graft-versus-host disease: Update on pathobiology, biomarkers, and evolving treatment algorithms.","authors":"Yibo Wu, Xiaolin Yuan, Jinya Lin, Yi Luo","doi":"10.1177/09636897261471702","DOIUrl":"10.1177/09636897261471702","url":null,"abstract":"<p><p>Chronic graft-versus-host disease (cGVHD) remains the leading cause of late non-relapse mortality and long-term disability after allogeneic hematopoietic cell transplantation (allo-HCT), affecting 30-70% of long-term survivors. Despite its substantial morbidity and the toxicities associated with prolonged corticosteroid use, therapeutic advances have accelerated considerably. This review synthesizes current mechanistic insights and clinical evidence within the framework of the well-established three-phase pathogenesis model of cGVHD. Phase 1 (early inflammation) involves tissue injury and innate immune activation; Phase 2 (months 2-12) is characterized by impaired central and peripheral tolerance with aberrant B- and T-cell responses; Phase 3 (>1 year) features macrophage-driven fibrosis and end-organ damage. Recognizing that these phases are conceptual and frequently overlap in clinical practice, we explore the alignment of contemporary biomarkers with each phase-ST2/CXCL9 (Phase 1), BAFF/autoantibodies (Phase 2), and MMP3/TGF-β (Phase 3)-and discuss how FDA-approved agents (ibrutinib, ruxolitinib, belumosudil, axatilimab) may target phase-specific pathways. A conceptual, risk-stratified treatment algorithm is proposed to link pathobiology to clinical decision-making, with the important caveat that biomarker-guided selection remains investigational and currently complements, rather than replaces, comprehensive clinical assessment. Notably, the adoption of prophylaxis and upfront strategies to prevent cGVHD has substantially reduced cGVHD incidence in modern cohorts.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261471702"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547935","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":"Muse cell transplantation attenuates neuroinflammation and preserves endothelial reparative responses after radiation-induced brain injury.","authors":"Xiaojie Wang, Zheng Sun, Shuang Li, Zhi Lu, Linli Zhang, Xiangqian Qi, Yue Wang, Changchuan Bai, Meiqing Lou, Chengbo Tan, Xiaonan Cui","doi":"10.1177/09636897261474028","DOIUrl":"10.1177/09636897261474028","url":null,"abstract":"<p><p>Radiation-induced brain injury (RIBI) is a serious complication of cranial radiotherapy and currently lacks effective disease-modifying treatment. Persistent neuroinflammation and neurovascular dysfunction are considered central to RIBI progression, making them attractive therapeutic targets for regenerative intervention. Multilineage-differentiating stress-enduring (Muse) cells are a non-tumorigenic pluripotent-like cell population with reported reparative and immunomodulatory properties, but their therapeutic potential in RIBI has not been defined. In this study, we evaluated the effects of Muse cell transplantation in experimental RIBI using in vitro neurovascular co-culture systems and in an vivo rat model. Irradiation induced marked activation of inflammasome-related signaling, endothelial injury, and neurological impairment. Muse cells suppressed the expression of NLRP3, AIM2, ASC, Caspase-1, IL-1β, and IL-18 in irradiated co-culture systems, while preserving endothelial proliferative and angiogenic responses. Transcriptomic analysis identified stress-related pathways associated with Muse cell-mediated protection, and PPAN emerged as a candidate regulator linked to the reparative phenotype. In vivo, intracarotid transplantation of Muse cells reduced [18F] DPA-714 uptake in irradiated brain tissue and was accompanied by supportive behavioral trends suggestive of functional improvement. These findings provide exploratory preclinical evidence that Muse cell transplantation attenuates neuroinflammatory activation and preserves endothelial reparative responses after radiation-induced brain injury. Muse cells may therefore represent a potential cell-based strategy for RIBI, although their therapeutic efficacy, neurovascular repair-related effects, and long-term functional benefits require further validation in larger and more comprehensive preclinical studies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261474028"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652949","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":"Regeneration of full-thickness cartilage defects using small umbilical cord-derived fast proliferating cells combined with magnesium in a rat model.","authors":"Jian Jiang, Min Ji Lee, Daeun Lee, Kwi-Hoon Jang, Tae Woo Kim, Chris Hyunchul Jo","doi":"10.1177/09636897251411597","DOIUrl":"10.1177/09636897251411597","url":null,"abstract":"<p><p>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 <i>in vitro</i>, in an uncontained <i>ex vivo</i> model, and via cell tracking in a rat FTD model. Therapeutic efficacy was evaluated using histological analyses of macroscopic and microscopic <i>in vivo</i> (at 4 and 8 weeks, n = 6). Mg²⁺ improved the adhesion of smumf cells by up to 1.89-fold in the <i>ex vivo</i> 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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251411597"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12799995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958963","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":"Effects of human embryonic stem cell-derived Schwann cells for nerve regeneration after facial nerve injury.","authors":"Myung Chul Yoo, Jong Ha Lee, Jae Min Lee, Yong Jun Kim, Seung Geun Yeo","doi":"10.1177/09636897261422301","DOIUrl":"10.1177/09636897261422301","url":null,"abstract":"<p><p>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 <i>in vitro</i> 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 (<i>P</i> < 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 (<i>P</i> < 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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261422301"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269718","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":"Evolution of mesenchymal stem cell therapies for traumatic brain injury: A decade of advances, mechanisms, and translational prospects.","authors":"Peining Zhu, Yufei Gao","doi":"10.1177/09636897261417625","DOIUrl":"10.1177/09636897261417625","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261417625"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716237","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":"Intranasal human neural stem cell therapy in early-onset Parkinson's disease with motor complications: A randomized, double-blind, placebo-controlled trial.","authors":"Kangwen Peng, Qiang Guan, Ronghua Hong, Yijing He, Fangyang Jiao, Tianyu Zhang, Ping Wu, Xiongfei Zhao, Qingfeng Zeng, Jingxing Zhang, Zujun Sun, Goulian Wei, Lingjing Jin","doi":"10.1177/09636897261494929","DOIUrl":"https://doi.org/10.1177/09636897261494929","url":null,"abstract":"<p><p>BackgroundTo evaluate the safety and efficacy of intranasal transplantation of ANGE-S003 human neural stem cells (hNSCs) in early-onset Parkinson's disease (EOPD) patients with motor complications.MethodsIn this randomized, double-blind, placebo-controlled trial, 24 EOPD patients were randomized (2:1) to receive weekly intranasal administrations of 1.5 × 10⁷ hNSCs or placebo for 4 weeks, followed by 12 months of follow-up. The primary endpoint was change in MDS-UPDRS Part IV score at month 6.ResultsNo significant difference was observed in the primary endpoint (least-squares mean difference, 0.42; 95% CI, -4.29 to 5.13; P = 0.853). Controls showed greater worsening of off-state MDS-UPDRS Part III motor scores in non-onset limbs at 12 months (P = 0.029). Exploratory 11C-CFT PET analyses demonstrated greater reductions in dopaminergic activity in the non-onset caudate (P = 0.022) and anterior putamen (P = 0.045) in controls versus the treatment group. A total of 137 adverse events and 6 serious adverse events were reported.ConclusionsAlthough the primary endpoint was not met, motor and neuroimaging findings provide preliminary signals of a potential treatment effect. Larger studies are needed to confirm efficacy and safety.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261494929"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179646","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":"The nude rat is capable of mounting a strong fibrotic response against cell-containing and cell-free subcutaneously implanted encapsulation devices.","authors":"Kelly M Pasowisty, Amy C Kelly, Trisha M Fabijanic, Leah V Steyn, Hannah A Hagen, Thomas Loudovaris, Robert C Johnson, Charles W Putnam, Klearchos K Papas","doi":"10.1177/09636897261424579","DOIUrl":"10.1177/09636897261424579","url":null,"abstract":"","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261424579"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200366","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":"Impact of Kellgren-Lawrence grade on clinical outcomes following adipose-derived stem cell therapy for knee osteoarthritis: A propensity score-matched retrospective cohort study.","authors":"Naoki Nakano, Tomoyuki Matsumoto, Masanori Tsubosaka, Tomoyuki Kamenaga, Kazunari Ishida, Rinako Osaka, Masaki Otsuji, Norimasa Nakamura, Yuichi Kuroda, Shinya Hayashi, Ryosuke Kuroda","doi":"10.1177/09636897251414212","DOIUrl":"10.1177/09636897251414212","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251414212"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12812197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988448","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":"Research progress and application prospect of engineered small extracellular vesicles.","authors":"Haoyu Zhang, Jian Chen, Xijie Tang, Xiangzhong Liu, Zhanghua Li","doi":"10.1177/09636897251409473","DOIUrl":"10.1177/09636897251409473","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251409473"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009011","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":"Salvage nintedanib plus low-dose ruxolitinib therapy for bronchiolitis obliterans syndrome refractory to calcineurin inhibitors and glucocorticoids after allogeneic transplantation.","authors":"Ya Luo, Ying Wu, Qiu-Sha Huang, Xian-Ying Yin, Qian-Nan Shang, Yi-Han Yang, Ao-Ran Zhang, Tong Su, Xiao-Han Su, Su-Xuan Liu, Zheng-Li Xu, Jing Liu, Xiao-Dong Mo, Yu-Qian Sun, Yu Wang, Meng Lv","doi":"10.1177/09636897261438731","DOIUrl":"10.1177/09636897261438731","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261438731"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615860","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}