Current stem cell research & therapy最新文献

{"title":"Application of Wharton's Jelly Derived from Human Umbilical Cord in Tissue Engineering.","authors":"Xiaoyang Hu, Weixuan Zhao, Jingdi Zhang, Yaping Shen, Wenjie Ren, Zhuo Liang","doi":"10.2174/011574888X462063260617052819","DOIUrl":"https://doi.org/10.2174/011574888X462063260617052819","url":null,"abstract":"<p><p>Tissue Engineering (TE) represents an effective approach for addressing tissue or organ defects and functional impairments. Cells, scaffolds, and growth factors, as the three elements of TE, play an important role in tissue repair. In recent years, there has been growing interest in Wharton's Jelly (WJ), obtained from the umbilical cord of postpartum medical waste. Mesenchymal stem cells, extracellular matrix, and growth factors derived from WJ have been widely used in TE. WJ has shown the potential to treat a wide range of diseases in clinical applications. This review discusses the mechanisms of action of WJ, focusing on their applications in the field of tissue damage repair. We also highlight the advantages, current limitations, and future directions of WJ-based therapies, including challenges related to standardization, scalability, long-term safety, and clinical translation.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational Age, Maternal Age, and Culture Dynamics Shape the Pluripotency Marker Profile of Primary Amniocytes: Insights for Stem Cell Biology and Regenerative Applications.","authors":"Ezgi Çokaklı, Mustafa Ertan Ay, Ümit Karakaş, Gurbet Doğru Özdemir, Kenan Çevik, Hüseyin Durukan, Mehmet Emin Erdal, Özlem İzci Ay","doi":"10.2174/011574888X442884260424071917","DOIUrl":"https://doi.org/10.2174/011574888X442884260424071917","url":null,"abstract":"<p><strong>Introduction: </strong>Amniotic Fluid Cells (AFCs) have emerged as a promising source for regenerative medicine due to their multipotent properties and accessibility. This study aimed to quantify pluripotency-associated transcript profiles in primary amniocyte cultures and evaluate their associations with gestational age, maternal age, and culture dynamics.</p><p><strong>Methods: </strong>This study analyzed the expression of ten pluripotency-associated genes (OCT3/OCT4, SOX2, KLF4, MYC, KIT, NANOG, DPPA3, DPPA5, FUT4, and SALL4) in primary AFC cultures derived from 17 pregnancies using quantitative real-time PCR (2-ΔΔCt; ACTB-normalized). Samples were evaluated according to gestational age, maternal age, and fetal sex; culture expandability was assessed based on the maximum passage achieved. AFC cultures were serially subcultured, and RNA was isolated independently at each available passage to quantify longitudinal passage-associated expression changes. Spearman's rank correlation assessed associations between gestational age and maternal age (continuous variables) and expression of SOX2, DPPA5, KIT, NANOG, and SALL4, with Benjamini-Hochberg FDR adjustment (q = 0.05).</p><p><strong>Results: </strong>All investigated markers were detectable across the AFC cultures. In group-based analyses, SOX2, DPPA3, and DPPA5 expression levels were higher in cultures derived from lower gestational ages, while SOX2 and DPPA5 were higher in younger maternal-age groups (p < 0.05). Culture expandability showed positive associations with KIT and selected markers. Serial-passaging analyses suggested that KIT expression was maintained in cultures achieving extended passaging, whereas SOX2 and DPPA5 expression tended to decrease with increasing passage number.</p><p><strong>Discussion: </strong>These findings indicate that developmental timing and in vitro culture dynamics are associated with variability in pluripotency-marker expression in primary amniocyte cultures. Transcript- level profiling may therefore help contextualize inter-individual heterogeneity and passagerelated shifts relevant to stem cell biology and standardized culture selection.</p><p><strong>Conclusion: </strong>AFC pluripotency-marker transcripts vary with gestational age, maternal age, and passaging. These transcript-level findings provide a quantitative reference but require protein/functional validation in larger, standardized cohorts.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Chimeric Antigen Receptor T-cell (CAR-T) Cell Therapy in Hematological Malignancies - A Systematic Review and Meta Analysis.","authors":"Ullas Mony, Vishnu Priya Veeraraghavan, Neeraj Sidharthan","doi":"10.2174/011574888X401292260530151340","DOIUrl":"https://doi.org/10.2174/011574888X401292260530151340","url":null,"abstract":"<p><strong>Introduction: </strong>CAR T therapy is used in various hematological malignancies that involve genetic modification of autologous T cells to target tumor cells. The aim of this meta-analysis was to evaluate the efficacy and safety of CAR T cell therapy in haematological malignancies with relation to response rates, survival outcomes, and treatment-related adverse events.</p><p><strong>Methods: </strong>This meta-analysis followed PRISMA guidelines. 428 records were identified from Pub- Med, Embase, Web of Science, Scopus, Cochrane Library, and Google Scholar for studies between 2019 and 2024. Clinical trials and observational studies evaluating CAR T therapy in haematological malignancies were included. Study quality was assessed using the Newcastle Ottawa Scale and ROBINS I tool. Random effects models were used, and heterogeneity was measured with the I² statistic.</p><p><strong>Results: </strong>Twelve studies met the inclusion criteria. CAR T therapy showed high ORR and CR in Bcell malignancies, with ORR reaching 90.5% in R/R B NHL and 81% remission in B ALL. CRS was common but mainly mild to moderate, while neurotoxicity and GvHD were less frequent. Metaanalysis demonstrated substantial heterogeneity for ORR, CR, and CRS. Most studies were rated good quality, though moderate bias related to missing data and design differences was observed.</p><p><strong>Discussion: </strong>Meta-analysis shows CAR T therapy achieves high ORR and durable remission in B ALL and DLBCL. CD19-directed therapy was promising. Compared to myeloid cell malignancies, B-cell malignancies showed better response. These findings point towards optimisation of protocol and appropriate patient selection apart from the toxicity management, which is required to improve the outcomes.</p><p><strong>Conclusion: </strong>CAR T therapy shows high response rates in haematological malignancies with controllable toxicity, thus establishing its role in relapsed and refractory disease. It highlights the need for improved durability, access, and constant clinical application.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cell-Derived Exosomes: A Novel Frontier in Regenerative Medicine and Immunotherapy.","authors":"Sami G Almalki","doi":"10.2174/011574888X442232260516190904","DOIUrl":"https://doi.org/10.2174/011574888X442232260516190904","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are a heterogeneous cell population that can be isolated from various tissues, including adipose tissue and bone marrow. Their ease of isolation and robust ex vivo expansion make MSCs an attractive candidate for regenerative and therapeutic applications, particularly in tissue repair and angiogenesis. Increasing evidence indicates that the therapeutic effects of MSCs are largely mediated through the secretion of extracellular vesicles, especially mesenchymal stem cell-derived exosomes (MSC-Exos). These exosomes contain diverse bioactive molecules, including proteins, nucleic acids, and lipids, which contribute to their regenerative, immunomodulatory, and therapeutic potential. Preclinical studies have demonstrated that MSC-Exos promote tissue repair, regulate immune responses, and alleviate pathological conditions associated with cardiovascular diseases, neurological disorders, musculoskeletal injuries, and immune-mediated diseases. The outcomes of these studies suggest that MSC-Exos represent a promising and effective therapeutic modality for a broad range of diseases. Compared with conventional MSC-based therapies, MSCExos offer several advantages, including reduced immunogenicity, lower tumorigenic risk, improved stability, and easier storage and handling, making them particularly suitable for clinical translation. This review provides a comprehensive overview of the current clinical and translational landscape of MSC-Exos therapy, highlighting their therapeutic applications, underlying mechanisms, and key challenges that must be addressed to facilitate successful clinical implementation. Collectively, the emerging evidence underscores the potential of MSC-Exos to advance regenerative medicine and suggests that exosome-based therapies may represent a transformative approach for the treatment of diverse human diseases.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of Mesenchymal Stromal Cells in Hematologic Disease: Advances, Challenges, and Bioengineering Strategies.","authors":"Yicheng Zhu, Chao Liu, Jing Yang","doi":"10.2174/011574888X453098260413210731","DOIUrl":"https://doi.org/10.2174/011574888X453098260413210731","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) are multipotent cells of mesodermal origin capable of self-renewal and multilineage differentiation. Characterized by low immunogenicity and tropism toward injury sites, MSCs exhibit critical properties including hematopoietic support, immunomodulation, and tissue regeneration. These unique attributes position MSCs as promising therapeutic tools for hematologic diseases, where disruption of the bone marrow niche impairs normal hematopoiesis. Co-transplantation of MSCs with hematopoietic stem cells (HSCs) facilitates HSC homing to the bone marrow niche and significantly improves post-transplant hematopoietic reconstitution. Furthermore, MSCs show considerable therapeutic potential in both prophylaxis and management of graftversus- host disease (GVHD), a major complication of allogeneic transplantation. The therapeutic mechanisms of MSCs have evolved from an initial focus on engraftment to a broader understanding of their paracrine actions via the \"hit-and-run\" mechanism, wherein MSCs exert functions through secreted factors and extracellular vesicles before host clearance. Despite these advances, clinical translation faces significant challenges, including poor homing efficiency, cellular heterogeneity, culture-induced senescence, and vulnerability to inflammatory and oxidative stress. This review summarizes clinical applications of MSCs in aplastic anemia, leukemia, and co-transplantation with HSCs, while critically evaluating the balance between therapeutic efficacy and potential risks. Additionally, we discuss emerging bioengineering strategies designed to overcome current limitations and enhance MSC therapeutic potency for next-generation cell therapies in hematologic diseases.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cells Improve the Prognosis of Sepsis Rats by Alleviating NLRP3-Caspase-1/Caspase-11-GSDMD-Mediated Pyroptosis of Peritoneal Macrophages.","authors":"Yunyu Yin, Kui Liu, Xuefeng Ding, Daqing Wang, Li Chen","doi":"10.2174/011574888X402548251208075156","DOIUrl":"https://doi.org/10.2174/011574888X402548251208075156","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a life-threatening condition and ranks among the leading causes of death worldwide. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as a therapeutic strategy for sepsis due to their anti-inflammatory and immune-regulatory properties. However, the precise molecular mechanisms by which BMSCs exert these beneficial effects in sepsis are not yet fully elucidated.</p><p><strong>Methods: </strong>We developed an in vitro macrophage injury model by co-culturing injured macrophages with BMSCs to evaluate pyroptosis. In vivo, we induced a sepsis model and subsequently transplanted BMSCs. The expressions of proteins involved in the NLRP3 (nod-like receptor family pyrin domain containing-3)-Caspase-1/Caspase-11-Gasdermin D (GSDMD) signaling pathway, as well as pyroptosis in peritoneal macrophages, were then investigated.</p><p><strong>Results: </strong>Our results demonstrated that BMSCs co-cultured with lipopolysaccharide (LPS)-stimulated macrophages improved macrophage viability and reduced pyroptosis in vitro. Moreover, transplantation of BMSCs significantly decreased pyroptosis in peritoneal macrophages and improved the survival rate of sepsis rats. BMSC treatment also downregulated the expression levels of pyroptosis-related proteins in macrophages isolated from sepsis rats, including NLRP3, Caspase-1, Caspase-11, and GSDMD.</p><p><strong>Discussion: </strong>These findings elucidate the mechanisms by which BMSCs exert therapeutic effects in sepsis, particularly through modulation of peritoneal macrophage pyroptosis. This provides a foundation for further research on sepsis and the potential clinical application of BMSCs. A limitation of this study is that the experimental results were derived from a rat model rather than non-human primates.</p><p><strong>Conclusion: </strong>This study demonstrates that transplantation of BMSCs may suppress NLRP3-Caspase- 1/Caspase-11-GSDMD-mediated pyroptosis in peritoneal macrophages during sepsis, providing new mechanistic insights into the therapeutic effects of BMSCs.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cell-derived Exosomes in Multicellular Regulation and Retinal Homeostasis Maintenance.","authors":"Bing Yang Lv, Anhuai Yang, Xuan Xiao","doi":"10.2174/011574888X443608260316054042","DOIUrl":"https://doi.org/10.2174/011574888X443608260316054042","url":null,"abstract":"<p><p>Retinal degenerative diseases like AMD and DR lead to irreversible vision loss through disrupted homeostasis. Mesenchymal Stem Cell-derived Exosomes (MSC-Exo), as a cell-free therapy, demonstrate significant potential in restoring retinal balance via multi-target regulation. This review elucidates the protective effects of MSC-Exo on key retinal cells, including pigment epithelium, endothelial cells, Müller glia, microglia, and ganglion cells, and specifically examines its role in modulating shared cellular pathways such as PI3K/AKT-Nrf2. It highlights a therapeutic cascade from vascular repair and anti-inflammation to neuroprotection, which coordinates intercellular interactions and promotes holistic retinal recovery. Finally, the review discusses the challenges and future clinical prospects of MSC-Exo-based therapies.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-Cytokine Preconditioning Reduces Senescence and Improves Immunomodulatory and Tissue Repair Capabilities of UC-MSCs.","authors":"Xiao-Qing Ji, He-Yi Zhang, Hang Li, Qin-Yi Su, Ting Cheng, Yue-Hong Huo, Rong-Rong Wang, Sheng-Xiao Zhang","doi":"10.2174/011574888X446369260224084745","DOIUrl":"https://doi.org/10.2174/011574888X446369260224084745","url":null,"abstract":"<p><strong>Introduction: </strong>Mesenchymal Stem Cells (MSCs) undergo prolonged in vitro passaging, which leads to cellular senescence, and this reduces their therapeutic effectiveness. This study aimed to investigate whether priming MSCs with a defined cytokine mix under hypoxic environments could reduce senescence and augment their therapeutic potential.</p><p><strong>Methods: </strong>Human umbilical cord-derived MSCs (UC-MSCs) at passage 4 (P4) and passage 8 (P8) were primed under hypoxic settings with three key cytokines (interferon γ, basic fibroblast growth factor, and leukemia inhibitory factor) for a duration of 24 h. We utilized flow cytometry, polymerase chain reaction, enzyme-linked immunosorbent assay, and other experimental approaches to examine the effects of passaging and priming on cellular properties, immunomodulatory capabilities, and neurotrophic qualities and angiogenic potentials.</p><p><strong>Results: </strong>At passage 8, UC-MSCs showed a loss of their usual spindle-shaped morphology, accompanied by an increase in size, a decrease in proliferative capacity, and a reduction in the expression of stemness-related genes, whereas markers of cellular senescence were enhanced. Nonetheless, priming strategies effectively reduced the expression of these senescence markers, maintained stemness, and augmented the expression of immunomodulatory cytokines, neurotrophic factors, and vasculogenic factors. Both UC-MSCs and primed UC-MSCs at P4 and P8 showed similar surface markers, indicating that neither serial expansion nor priming changed the fundamental immunophenotype of the MSCs.</p><p><strong>Discussion: </strong>The results show that hypoxia-cytokines priming effectively mitigates senescence caused by expansion while keeping their immunophenotype. This strategy not only maintains stem cell properties but also enhances their therapeutic potential, making it a feasible approach to obtain large numbers of highly active MSCs for clinical applications.</p><p><strong>Conclusion: </strong>In summary, hypoxia-cytokine priming delayed cellular senescence and possibly enhanced the immunomodulatory, neurotrophic, and vasculogenic properties of UC-MSCs.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pretreatment of Conditioned Medium from Inflammatory Macrophages Amplifies Umbilical Cord Mesenchymal Stem Cell Efficacy and Diminishes Macrophage Crosstalk in Colitis.","authors":"Chen Wang, Qin Chen, Sen He, Xiaodong Zhou, Kaifeng Zhang, Xinguo Zhu","doi":"10.2174/011574888X408637251124100536","DOIUrl":"https://doi.org/10.2174/011574888X408637251124100536","url":null,"abstract":"<p><strong>Introduction: </strong>The hostile inflammatory microenvironment at the injury site often limits the therapeutic potential of human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) in colitis. To address this challenge, we explored whether priming UC-MSCs with conditioned medium from M1 macrophages (M1-CM) could attenuate detrimental macrophage crosstalk and amplify their immunomodulatory efficacy, improving overall treatment outcomes.</p><p><strong>Methods: </strong>The M1 macrophage phenotype was induced with LPS and IFN-γ, and M1-CM was collected. UC-MSCs were preconditioned with M1-CM to generate M1UC-MSCs. To assess the therapeutic potential of M1UC-MSCs, a dextran sulfate sodium (DSS)-induced colitis model was established in ICR mice.</p><p><strong>Results: </strong>Preconditioning with M1-CM significantly enhanced the anti-inflammatory properties of UC-MSCs without compromising viability. In vivo, M1UC-MSCs exhibited improved survival and more effectively ameliorated colitis symptoms, reducing disease severity and inflammatory damage compared to non-primed cells.</p><p><strong>Discussion: </strong>These results indicate that inflammatory preconditioning augments the therapeutic function of UC-MSCs by enhancing their adaptability and reducing deleterious interplay with macrophages. This approach is consistent with current strategies to improve cellular tolerance and microenvironmental compatibility. Study limitations include the need for further mechanistic investigation, and subsequent research should prioritize elucidating the specific molecular pathways modulating macrophage-MSC crosstalk.</p><p><strong>Conclusion: </strong>M1-CM preconditioning represents a novel and potent strategy to enhance UC-MSCbased therapy for colitis, primarily by improving cellular adaptation and harmonizing the immune response under inflammatory conditions. This method holds significant promise for advancing regenerative medicine applications in colitis.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Doses of Overexpression of Cellular Prion Protein in Adipose-derived Mesenchymal Stem Cells Safely Provided Additional Protection to the Lungs Against Bleomycin-induced Damage in Rodents.","authors":"Kun-Chen Lin, Jui-Ning Yeh, Yi-Ling Chen, John Y Chiang, Chi-Ruei Huang, Yi-Ting Wang, Jun Guo, Hon-Kan Yip","doi":"10.2174/011574888X416268251210125540","DOIUrl":"https://doi.org/10.2174/011574888X416268251210125540","url":null,"abstract":"<p><strong>Introduction: </strong>We tested whether early administration of multiple doses of adipose-derived mesenchymal stem cells (ADMSCs) overexpressing cellular prion protein (PrPC-OVE) could preserve lung parenchyma and function in a rodent model of bleomycin-induced pulmonary fibrosis (PF).</p><p><strong>Methods: </strong>Cell culture, immunohistochemistry, immunofluorescence, and western blot analyses were conducted. Animals were categorized into sham-control (Group 1), PF (Group 2), PF + ADMSCs (one dose; Group 3), PF + ADMSCs (three doses; Group 4), PF + PrPC-OVE in ADMSCs (one dose; Group 5), and PF + PrPC-OVE in ADMSCs (three doses; Group 6).</p><p><strong>Results: </strong>In vitro, bleomycin suppressed L2 cell proliferation and increased apoptosis and epithelial-mesenchymal transition (EMT) markers, which were significantly reversed by ADMSCs and further enhanced by PrPC-OVE in ADMSCs. TGF-β/Smads signaling-mediated EMT was identified as a crucial mechanism in cellular fibrosis and PF, which was significantly suppressed by silencing TGF-β in L2 cells and PrPC-OVE in ADMSCs co-cultures and lung tissue. By days 28 and 42 after PF induction, O₂ saturation (%) was highest in Group 1, lowest in Group 2, and notably higher in Group 6 than in Groups 3-5. Right-ventricular (RV) systolic blood pressure showed an inverse trend. RV and left lung weights-to-tibial length ratios were significantly greater in Group 2 at both time points. By day 42, Group 2 exhibited the highest lung injury, fibrosis, and protein levels of fibrotic, EMT, inflammatory, and oxidative stress markers, whereas these parameters were lowest in Group 1 and significantly higher in Group 4 than in Group 6.</p><p><strong>Discussion: </strong>This study, which investigated the therapeutic role of PrPC-OVE in ADMSCs in protecting lung parenchyma against bleomycin-induced damage, provides several important preclinical insights. First, the in vitro study demonstrated that bleomycin activated TGF-β/Smads signaling, inducing EMT upregulation in lung epithelial cells (L2 cell line), which plays a crucial role in the initiation and propagation of PF. Second, both in vitro and in vivo studies showed that PrPC-OVE played a fundamental role in attenuating bleomycin-induced PF, mainly through regulation of TGF-β/Smads signaling. Third, ADMSCs were less effective than PrPC-OVE in ADMSCs, and repeated doses of ADMSCs were less effective than repeated doses of PrPC-OVE in ADMSCs in protecting lung function and parenchyma against bleomycin-induced damage.</p><p><strong>Conclusion: </strong>Repeated PrPC-OVE-ADMSCs effectively preserved lung function and parenchyma by suppressing TGF-β/Smads signaling in bleomycin-induced PF.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}