Stem Cell Research & Therapy最新文献

{"title":"Advances in the clinical application of mesenchymal stem cells for neurological disorders.","authors":"Mohammad Chand Jamali, Alaa Shafie, Ali Jaber Alqahtani, Rithab Ibrahim Al-Samawi, Hanan Mesfer Alyami, Amal Adnan Ashour, Mohammed Fareed Felemban, Nasrin Mansuri, Faris J Tayeb, Irshad Ahmad, Mustafa Mudhafar, Salah Ahmed Sheweita","doi":"10.1186/s13287-026-05229-5","DOIUrl":"10.1186/s13287-026-05229-5","url":null,"abstract":"<p><p>Therapeutic approaches employing mesenchymal stem cells (MSCs) have emerged as a promising avenue for investigating treatments for neurological disorders. This strategy aims to capitalize on the biological properties of MSCs to support the repair of damaged neural tissue and modulate pathological processes. This review provides a comprehensive overview of the current clinical evidence regarding MSC applications in major neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other pertinent disorders. Across clinical studies, MSC administration has generally demonstrated a favorable safety profile and procedural feasibility. However, therapeutic efficacy remains variable and inconsistent across trials. Importantly, differences in MSC sources, manufacturing procedures, delivery routes, dosing strategies, and patient selection contribute substantially to the heterogeneity of reported outcomes. Therefore, the current body of evidence supports the safety of MSC-based interventions, but their clinical effectiveness has not yet been consistently demonstrated. Future progress will depend largely on the standardization of cell preparation and treatment protocols, improved biomarker-driven patient stratification, and rigorously designed large-scale randomized trials.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell-based therapies in pediatric disorders: translational advances, unresolved challenges, and future horizons.","authors":"Hany E Marei","doi":"10.1186/s13287-026-05204-0","DOIUrl":"10.1186/s13287-026-05204-0","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Pediatric disorders consist of genetic, hematologic, neurologic, autoimmune, and inflammatory diseases. These conditions impose long-term health challenges on children, despite many advancements with conventional medicine. Although conventional treatments increase life expectancy and provide better disease control, many present challenges such as toxicity, insufficient control of the disease, and adverse effects on normal growth, development, and quality of life. Many researchers have shown increased interest in using stem cell therapies as an alternative to current medications to allow for complete, sustainable repair of damaged tissues and modification of disease processes (i.e., using stem cells to regenerate tissue or change the way in which a disease occurs). This paper will provide the current information on stem cells used in the treatment of children and the many different types of stem cells, including: hematopoietic stem cells (and their derivatives), mesenchymal stem cells (and their derivatives), induced pluripotent stem cells, embryonic stem cells, tissue-specific progenitor cells, extracellular vesicles, and bioengineered products. This paper will also discuss what is known about the stem cells listed as well as their methods of action, where they might currently be better utilized, and future uses of these cells in children for a variety of types of pediatric diseases. Because each stem cell type listed has very different scientific background and clinical evidence, there is much variability in the amount of scientific evidence available to support stem cell therapies. For example, hematopoietic stem cell transplantation (HSCT) has over 50 years of clinical experience; thus, there are many studies defining the clinical efficacy and long-term outcomes associated with HSCT. Conversely, while there are many published studies supporting the use of mesenchymal stem cells (MSCs), extracellular vesicles (EVs), gene-edited cells, organoids, and many induced pluripotent stem cell-derived therapies, more evidence (clinical and basic science) is still needed to fully establish efficacy for the use of these various stem cells in children with pediatric diseases. In addition to needing more clinical evidence, stem cell-based therapies face many important challenges to the advancement of these therapies, including (but not limited to) long-term safety assessments, manufacturing standardization, regulatory oversight, ethical concerns, and equitable access to advanced therapies. Addressing these challenges will be important for future advances in the use of regenerative medicine in pediatric patients which will also require the rigorous evaluation of new stem cell therapies, the continued improvement of translational mechanisms, and the ongoing incorporation of new techniques (e.g., genome editing, organoid modeling, EV therapeutics, bioengineering, and artificial intelligence) to advance regenerative medicine and demonstrate its value throu","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single-donor proof-of-concept single-cell analysis maps heterogeneous differentiation trajectories toward cartilage-like states in human urine-derived stem cells.","authors":"Alexander Schulz, Emily M Brockmann, Miriam Zentgraf, Andreas S Baur, Steffen Uebe, Arif B Ekici, Mark Dedden, Sebastian Zundler, Christian T Thiel","doi":"10.1186/s13287-026-05223-x","DOIUrl":"10.1186/s13287-026-05223-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Urine-derived stem cells (USCs) represent an accessible and non-invasive cell source with reported chondrogenic differentiation potential. However, the cellular heterogeneity and transcriptional dynamics underlying USC differentiation remain incompletely understood, limiting their translational interpretation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We combined functional differentiation assays with single-cell RNA sequencing to characterize USC differentiation at both phenotypic and transcriptional levels. Chondrogenic and osteogenic differentiation were assessed using histological staining, quantitative PCR, and three-dimensional spheroid cultures. Single-cell transcriptomic analysis was performed on integrated datasets of undifferentiated and differentiated USCs, followed by pseudotime trajectory inference and mapping to a human cartilage reference atlas.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Chondrogenic induction resulted in reproducible acquisition of cartilage-associated features, including glycosaminoglycan-rich extracellular matrix deposition, increased expression of SOX9, and formation of aggrecan-positive spheroids. In this donor, single-cell analysis mapped an inferred differentiation trajectory from proliferative states towards differentiated populations, although the fine-grained pseudotemporal ordering was sensitive to analytical choices and is therefore interpreted qualitatively. Along this inferred trajectory, we identified a candidate transient transcriptional state associated with elevated CDH1 expression and epithelial-like aggregation features. Probabilistic mapping to a human cartilage reference atlas indicated that overall mapping confidence was low (median prediction score 0.34) and that only a minority of cells showed confident transcriptional similarity (prediction score ≥ 0.5) to mature/articular cartilage-associated reference states (7.8% of all cells and 17.6% of chondrogenically induced cells). This confident similarity was concentrated in a few clusters at the differentiated end of the trajectory rather than representing the bulk of the culture, and label-transfer confidence was not equated with chondrocyte identity. Despite this enrichment, differentiated populations exhibited transcriptional heterogeneity, including subsets of cells associated with hypertrophic, fibrocartilage-like, and contractile gene programmes, indicating the presence of multiple differentiation trajectories.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This single-donor proof-of-concept study suggests that USC differentiation may involve a candidate transient, aggregation-associated transcriptional state accompanied by CDH1 expression and gives rise to heterogeneous lineage-associated outcomes, with only a minority of cells acquiring confident transcriptional similarity to mature cartilage. Because these observations derive from one donor, they should be interpreted as hypothesis-generating and require validation across independent d","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow-derived mesenchymal stem cells for ischemic stroke: mechanisms, delivery strategies, clinical evidence, and translational challenges.","authors":"Wenjing Zhang, Haoqun Xu, Fengwei Guo, Zhaoqi Zhang, Wei Liu","doi":"10.1186/s13287-026-05219-7","DOIUrl":"10.1186/s13287-026-05219-7","url":null,"abstract":"<p><p>Ischemic stroke remains a major global health burden because of its high incidence, disability, and mortality. Current reperfusion therapies are constrained by narrow therapeutic windows and have limited capacity to reverse established neuronal injury or promote long-term functional recovery, highlighting the need for strategies that support neural repair and neurovascular remodeling. Bone marrow-derived mesenchymal stem cells (BMSCs) have been widely investigated as candidate therapeutic products for ischemic stroke because of their paracrine, immunomodulatory, trophic, angiogenic, and microenvironment-regulating properties. Current evidence suggests that their therapeutic effects are more likely mediated by regulation of the post-ischemic microenvironment than by direct neuronal replacement. This narrative review discusses BMSC-based strategies for ischemic stroke by integrating evidence from preclinical models, early clinical studies, and translational research. We summarize major proposed mechanisms, including regulation of neuroinflammation, suppression of apoptosis and oxidative stress, blood-brain barrier protection, angiogenesis, neurotrophic support, axonal remodeling, and myelin repair. Emerging mechanisms, such as autophagy regulation, mitochondrial transfer, and extracellular vesicle-mediated effects, are also discussed according to their current level of evidence. In addition, this review evaluates delivery routes, functional enhancement strategies, BMSC-derived extracellular vesicles, combination approaches, clinical evidence, and key translational barriers. Particular attention is given to the distinction between experimentally supported mechanisms, early clinical safety and feasibility signals, and unresolved issues related to optimal dose, administration timing, route-dependent biodistribution, product heterogeneity, mechanism-linked potency assays, and Good Manufacturing Practice-compatible manufacturing. This review provides a balanced framework for understanding the therapeutic potential, current limitations, and future development requirements of BMSC-based therapies for ischemic stroke.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-released growth factors promote pro-angiogenic effects in endothelial cells: a translational perspective on wound healing and regenerative medicine.","authors":"Michael Singh, Karina Zitta, Thilo Wedel, Ralph Lucius, François Cossais, Peter Behrendt, Sabine Fuchs, Jan-Tobias Weitkamp, Rouven Berndt, Olga Zimmermann, Tim Schricker, Andreas Bayer, Martin Albrecht","doi":"10.1186/s13287-026-05214-y","DOIUrl":"10.1186/s13287-026-05214-y","url":null,"abstract":"<p><p>Platelet-Released Growth Factors (PRGF) are a standardized, cell- and fibrin-free platelet lysate with translational potential for tissue repair. PRGF enhance tissue regeneration, particularly in contexts where angiogenesis is critical for restoring perfusion in chronic and non-healing wounds. Here, we present the first in vitro study demonstrating that PRGF exert pro-angiogenic effects at a working concentration of 10%. The study employs an endothelial cell-based model integrating targeted gene expression analysis, array-based profiling of angiogenesis-related proteins, and functional endothelial tube formation assays. In this setting, screening-level transcriptional and proteomic profiling indicated higher transcript levels of angiogenesis-related genes and increased signals of representative angiogenesis-associated mediators (e.g., Platelet Factor 4, Angiopoietin-1, Angiogenin) following PRGF stimulation. Functional tube formation assays demonstrated significant enhancement of multiple pro-angiogenic parameters in response to PRGF, including number of pieces (P < 0.001), junctions (P < 0.01), and segments (P < 0.05). These findings suggest that 10% PRGF may support angiogenesis and tissue regeneration and provide a foundation for further validation in more complex multicellular systems and in vivo models.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secreted protein combination GAPDH/S100A8/S100A9 from human expanded potential stem cells counteracts mesenchymal stromal cell senescence.","authors":"Qingcai Feng, Qianwen Pang, Hongyu Lu, Zijing Liu, Zhancheng Lin, Zhou Songyang, Feng Liu, Guang Shi","doi":"10.1186/s13287-026-05178-z","DOIUrl":"10.1186/s13287-026-05178-z","url":null,"abstract":"<p><strong>Background: </strong>Human mesenchymal stromal cells (hMSCs) remain the most clinically advanced adult stem cell source; however, their therapeutic potential is limited by rapid replicative senescence during ex vivo expansion. Replicative senescence in hMSCs is characterized by cell cycle arrest, acquisition of senescence-associated β-galactosidase (SA-β-Gal) activity, and secretion of the senescence-associated secretory phenotype (SASP) factors.</p><p><strong>Methods: </strong>We investigated whether conditioned medium derived from human extended pluripotent stem cells (hEPSCs), which possess both embryonic and extra-embryonic developmental potential beyond that of conventional embryonic stem cells (hESCs), could attenuate replicative senescence in human Wharton's Jelly-derived MSCs (WJMSCs). Using sequential ultrafiltration (10 kDa and 3 kDa) followed by liquid chromatography-tandem mass spectrometry, we identified several proteins from hEPSC-conditioned medium. We then tested the combination of S100A9/GAPDH/S100A8 proteins for their effects on doxorubicin (DOXO)-induced and replicative senescence.</p><p><strong>Result: </strong>hEPSC-conditioned medium markedly attenuated replicative senescence in hMSCs. Notably, the combination of S100A9/GAPDH/S100A8 proteins not only mitigated doxorubicin-induced senescence but also counteracted replicative senescence, as evidenced by a significant reduction in SA-β-Gal-positive cells and downregulated mRNA expression of senescence-associated genes, including p16, p21, and the SASP factor IL-6. Furthermore, EdU incorporation assays revealed significantly enhanced proliferative capacity following treatment.</p><p><strong>Conclusions: </strong>Collectively, our findings establish a defined protein combination (S100A9/GAPDH/S100A8) that counteracts both replicative and stress-induced senescence, offering a novel, cell-free strategy to enhance the clinical utility of WJMSCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Mesenchymal stem cells inhibit mitochondrial fission by upregulating armadillo repeat containing 1, ameliorating oxidative stress in renal fibrosis.","authors":"Tao Li, Chuan Guo, Qin Liu, Fengting Jing, Min Zhao, Hemin Xiong, Chang Li, Wei Zhang, Bo Chen","doi":"10.1186/s13287-026-05164-5","DOIUrl":"10.1186/s13287-026-05164-5","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13422301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond conventional PRP: a rationale for bioengineered, growth-factor-defined platelet mimetics in alopecia-the precision re-engineered efficacy optimization framework.","authors":"Rinky Kapoor, Raji Patil, Debraj Shome, Prashant Anilkumar Singh, Debalina Bose, Alivia Basu, M S Sukesh, Imran Ali, Michael Gold","doi":"10.1186/s13287-026-05147-6","DOIUrl":"10.1186/s13287-026-05147-6","url":null,"abstract":"<p><p>Autologous platelet-rich plasma (PRP) is widely used for alopecia, but outcomes are often inconsistent due to procedural differences and patient-to-patient biological variability, including platelet yield, leukocyte content, and the mixed presence of stimulatory and inhibitory mediators. This commentary outlines a rationale for moving from variable autologous PRP toward defined PRP-inspired, growth-factor-based platelet mimetic formulations with batch-specified concentrations and relative proportions to enable more reproducible dosing and clearer clinical evaluation, aligned with Precision Re-Engineered Efficacy Optimization as a framework for standardizing potency, composition, and performance. Such formulations may improve consistency and scalability, but should be viewed as controlled reconstructions of selected PRP-associated signals rather than complete replicas of platelet releasate. Their translational value will depend on careful formulation characterization, staged proof-of-concept testing, and controlled clinical studies to establish safety, dosing, and comparative effectiveness.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous placenta-derived mesenchymal stem cells enhance early survival as an adjunct to supportive care in severe burn: a preclinical study.","authors":"Eng-Kean Yeong, Houng-Chi Liou, Yan Ting Liou, Chin-Hao Chang, Yu-Xiu Lin, Thai-Yen Ling","doi":"10.1186/s13287-026-05053-x","DOIUrl":"10.1186/s13287-026-05053-x","url":null,"abstract":"<p><strong>Background: </strong>Severe burn injury induces a rapid systemic inflammatory response, and early survival depends heavily on timely fluid resuscitation and thermal support. However, optimal supportive care may be difficult to deliver in austere or resource-limited environments. Placenta-derived choriodecidual mesenchymal stem cells (pcMSCs) possess immunomodulatory properties and may improve outcomes when supportive care is suboptimal. This study investigated whether intravenous pcMSC therapy improves early survival after severe burn injury in a preclinical model.</p><p><strong>Methods: </strong>Sixty adult male Sprague-Dawley rats underwent standardized 40% total body surface area full-thickness burns and were randomly assigned to six groups (n = 10/group) differing in fluid resuscitation (1× vs. 3× Ringer's lactate), thermal support (heating lamp vs. incubator warming), and intravenous pcMSC therapy. Survival was monitored for 14 days and analyzed using Kaplan-Meier methods with log-rank testing. Serum TNF-α, IL-1β, and IL-6 levels, body weight, water intake, and core body temperature were assessed longitudinally in selected groups.</p><p><strong>Results: </strong>Survival differed significantly among groups, with 93% of deaths occurring within the first 3 days post-burn. Under low-volume resuscitation, survival declined to 30% in untreated animals and improved to 50% with pcMSC therapy, indicating a survival benefit under insufficient resuscitation conditions. With adequate fluid resuscitation and thermal support, survival was high without pcMSCs (80%) and numerically higher with pcMSCs (90%), although this difference was not statistically significant after adjustment. Thermal support exerted a marked effect on outcomes, with warmed animals demonstrating substantially higher survival despite similar or lower fluid volumes. PcMSC treatment attenuated post-burn hypothermia, reduced weight loss and dehydration, and significantly decreased circulating TNF-α, IL-1β, and IL-6 levels.</p><p><strong>Conclusions: </strong>Placenta-derived choriodecidual mesenchymal stem cells may confer an additive survival benefit after severe burn injury, particularly under inadequate fluid resuscitation and thermal support, likely through stabilization of body temperature, improved hydration, and attenuation of systemic inflammation, supporting their potential role as an adjunctive therapy in austere or resource-limited settings.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administration of injectable platelet-rich fibrin improved repair of thin endometrium via mitochondria in a rat model.","authors":"Haiqing Tian, Yixuan Zhu, Haozhe Ma, Nan Su, Manli Zhang, Xiaolin La, Lei Cui, Zijian Zhang, Jing Dong, Mengjie Zhang","doi":"10.1186/s13287-026-05181-4","DOIUrl":"https://doi.org/10.1186/s13287-026-05181-4","url":null,"abstract":"<p><strong>Background: </strong>Thin endometrium(TE) has been widely recognized as a critical factor contributing to reduced success rates of assisted reproductive technology (ART). In recent years, platelet-rich plasma (PRP) has been extensively employed in the treatment of thin endometrium; however, its underlying mechanisms remain poorly understood, and its clinical efficacy remains controversial. Given the superior therapeutic outcomes demonstrated by platelet concentrates (PCs) in regenerative medicine, the present study aimed to investigate the therapeutic potential and mechanistic basis of injectable platelet-rich fibrin (i-PRF) in an ethanol‑induced rat model of thin endometrium.</p><p><strong>Methods: </strong>i-PRF was prepared from human blood and characterized for growth factor release and microstructure. Rats were divided into control, Model, Ethanol + NS, and Ethanol+i-PRF groups.Endometrial morphology was assessed by H&E and immunohistochemistry. Receptivity was evaluated by LIF/VEGF expression and embryo implantation counts. In vitro, endometrial stromal cells (ESCs) were co-cultured with platelets, and mitochondrial transfer was tracked using MitoTracker^®. Platelet mitochondrial respiration was inhibited with oligomycin/FCCP to assess functional contribution.</p><p><strong>Results: </strong>i-PRF released VEGF-A, TGF-β1, and PDGF-AB for up to 15 days (peak at 7 days), with a dense fibrin network entrapping abundant platelets. Ethanol injection significantly reduced endometrial thickness from 409.27 ± 55.86 μm to 104.48 ± 57.03 μm and decreased gland number from 22.4 ± 4.34 to 9.2 ± 3.77 (both p < 0.05).Administration of i-PRF reversed these pathological changes, restoring endometrial thickness to 464.11 ± 27.1 μm and gland count to 29.0 ± 9.41 (*p* < 0.05 vs. model). Immunohistochemical analysis revealed that i-PRF treatment increased the abundance of vimentin⁺,cytokeratin 18⁺ (CK-18⁺) and ki-67⁺ cells and enhanced the expression of leukemia inhibitory factor (LIF) and vascular endothelial growth factor (VEGF). Compared with the model group, the Ethanol + i‑PRF group exhibited a markedly higher embryo number (3.88 ± 3.91, P < 0.001); although this value was lower than that of the control group (5.00 ± 3.46), the difference did not reach statistical significance (P > 0.05).  In vitro co-culture of endometrial stromal cells (ESCs) with platelets promoted ESC proliferation and VEGF secretion. Confocal microscopy confirmed the direct transfer of platelet mitochondria to ESCs. Inhibition of platelet mitochondrial respiration did not block ESC proliferation but significantly suppressed VEGF and vimentin expression (p < 0.05).</p><p><strong>Conclusions: </strong>i-PRF effectively repairs thin endometrium in a rat model, and mitochondrial transfer from platelets to ESCs plays a key role in promoting endometrial regeneration. These findings support i-PRF as a promising therapy for TE.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}