Stem Cell Research & Therapy最新文献

{"title":"The PAR6B-PRKCI-PAR3 complex influences alveolar regeneration in patients with the emphysema subtype of chronic obstructive pulmonary disease.","authors":"Di Wang, Hongbo Liu, Shuang Bai, Xuejian Zheng, Li Zhao","doi":"10.1186/s13287-025-04189-6","DOIUrl":"10.1186/s13287-025-04189-6","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is gaining increasing attention, with different subtypes being distinguished for separate research and treatment. The emphysema subtype is characterized by widespread alveolar destruction, which may be associated with aggravated alveolar damage and abnormal repair. Type II alveolar epithelial cells (AEC2s), known for their stem cell potential, have recently emerged as a promising target for COPD treatment. However, to date, few studies have elucidated the specific mechanisms by which AEC2s induce alveolar regeneration.</p><p><strong>Methods: </strong>Lung tissue samples from COPD patients were collected, and bioinformatics analysis was used to identify expression profiles affecting the emphysema phenotype and target genes regulating AEC2 proliferation. In vitro models of smoke-induced injury and viral transfection were established to clarify the role of the target gene PARD6B in regulating AEC2s proliferation and transdifferentiation potential. Co-immunoprecipitation and mass spectrometry were employed to elucidate the specific regulatory mechanisms. Primary mouse AEC2s were isolated for 3D spheroid formation experiments to further validate the role of the target gene.</p><p><strong>Results: </strong>We observed impaired self-proliferation and enhanced transdifferentiation of AEC2s into AEC1s in lung tissues from COPD patients with emphysema subtype, which was associated with reduced expression of PARD6B. Interestingly, PARD6B primarily functioned as part of a complex in AEC2s. Mechanistically, we found that reduced levels of the PAR3-PARD6B-PRKCI complex could arrest the cell cycle of AEC2s in the G0-G1 phase, thereby impairing their self-proliferation.</p><p><strong>Conclusions: </strong>Our findings reveal a novel regulatory mechanism for alveolar regeneration, highlighting a potential therapeutic target for managing the emphysema subtype of COPD.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"97"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504272","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":"aFGF gene-modified adipose-derived mesenchymal stem cells promote healing of full-thickness skin defects in diabetic rats.","authors":"Yiren Zhu, Pinhua Chen, Zhengchao Zhang, XueYi He, Ruoli Wang, Qi Fang, Zhixian Xu, Wubing He","doi":"10.1186/s13287-025-04241-5","DOIUrl":"10.1186/s13287-025-04241-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic diabetic wounds pose a significant clinical challenge due to the limited efficacy of current treatments. This study aimed to investigate the role and potential mechanisms of adipose-derived mesenchymal stem cells (ADSCs) overexpressing acidic fibroblast growth factor (aFGF) in diabetic wound healing in a rat model.</p><p><strong>Methods: </strong>ADSCs were genetically modified to achieve stable overexpression of aFGF. Varying doses of aFGF-ADSCs (1 × 10⁶, 2 × 10⁶, 3 × 10⁶, 4 × 10⁶) were injected into the muscular tissue surrounding diabetic rat wounds. We assessed aFGF expression and its impact on various stages of wound healing, including angiogenesis, inflammatory response, epithelialization, and collagen deposition. Transcriptomic sequencing was performed to explore the underlying mechanisms driving enhanced wound healing.</p><p><strong>Results: </strong>Lentiviral transduction successfully induced stable aFGF overexpression in ADSCs. In vivo experiments revealed that varying doses of aFGF-ADSCs markedly enhanced wound healing in diabetic rats in a dose-dependent manner. The dose of 3 × 10⁶ aFGF-ADSCs demonstrated the most significant effect. In the 3 × 10⁶ aFGF-ADSCs group, expression levels of aFGF, CD31, and CD163 were significantly higher than in other groups (p < 0.05), while CD86 expression was significantly lower (p < 0.05).</p><p><strong>Conclusion: </strong>Single doses of aFGF-ADSCs comprehensively improved various aspects of wound repair in diabetic rats, offering a potential new approach for treating chronic diabetic wounds. The mechanism of action involves promoting angiogenesis, modulating inflammatory responses, accelerating epithelialization, and optimizing collagen deposition.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"93"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503899","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":"Long-term outcomes of mesenchymal stem cell therapy in severe COVID-19 patients: 3-year follow-up of a randomized, double-blind, placebo-controlled trial.","authors":"Meng-Qi Yuan, Le Song, Ze-Rui Wang, Zi-Ying Zhang, Ming Shi, Junli He, Qiong Mo, Ning Zheng, Wei-Qi Yao, Yu Zhang, Tengyun Dong, Yuanyuan Li, Chao Zhang, Jinwen Song, Lei Huang, Zhe Xu, Xin Yuan, Jun-Liang Fu, Cheng Zhen, Jianming Cai, Jinghui Dong, Jianzeng Zhang, Wei-Fen Xie, Yonggang Li, Bo Zhang, Lei Shi, Fu-Sheng Wang","doi":"10.1186/s13287-025-04148-1","DOIUrl":"10.1186/s13287-025-04148-1","url":null,"abstract":"<p><strong>Background: </strong>The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years.</p><p><strong>Methods: </strong>One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n = 65, 4 × 10⁷ cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection.</p><p><strong>Results: </strong>Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 0.65-4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44-24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China's dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR = 0.54, 95% CI: 0.20-1.41).</p><p><strong>Conclusions: </strong>These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102 .</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"94"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504262","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":"Reducing PDK4 level constitutes a pivotal mechanism for glucocorticoids to impede osteoblastic differentiation through the enhancement of ferroptosis in mesenchymal stem cells.","authors":"Yue Jiang, Ai-Hua Ye, Wen-Ge He, Lu Liu, Xiang Gao, Hang Liu, Wen-Ting Liu, Fang-Lin Ye, Dong-Mei He, Jun-Yi Liao, Jing Wang, Bai-Cheng He","doi":"10.1186/s13287-025-04186-9","DOIUrl":"10.1186/s13287-025-04186-9","url":null,"abstract":"<p><strong>Background: </strong>This study mainly explores the possible role and mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in the onset and development of Glucocorticoid-induced osteoporosis (GIOP), and seeks potential targets for the treatment of GIOP.</p><p><strong>Methods: </strong>Mesenchymal stem cells (MSCs) were treated with osteogenic induction medium. An in vitro osteogenic damage model was established by exposing MSCs to a high concentration (10^- 6 M) of dexamethasone (DEX). Osteogenic markers were measured with real-time quantitative polymerase chain reaction, western blot, alkaline phosphatase staining, and Alizarin Red S staining. Ferroptosis markers were assessed through reactive oxygen species (ROS) fluorescent probe, transmission electron microscopy, and measurement of malondialdehyde (MDA). The potential mechanism was investigated using RT-qPCR, western blot, lysosomal probes, molecular docking, and other analytical approaches. The role of PDK4 was validated by using a GIOP rat model, micro-computed tomography and Masson's trichrome staining.</p><p><strong>Results: </strong>High concentrations (10^- 6 M) of DEX inhibited osteogenic differentiation in C3H10T1/2 cells, and PDK4 exhibited the opposite effect. PDK4 partially reversed the osteogenic inhibitory effect of DEX both in vivo and in vitro. DEX caused mitochondrial shrinkage and disappearance of cristae in C3H10T1/2 cells, as well as an increase in total iron, ROS, MDA contents, and the level of ferroptosis key factors. These changes were partially weakened by PDK4. The ferroptosis inhibitor ferrostatin-1 partially blocked the inhibitory effect of DEX, while ferroptosis inducer RSL3 inhibited osteogenic differentiation and weakened the reversal effect of PDK4. DEX reduced the protein level of PDK4, which was partially weakened by Bafilomycin A1. The molecular docking results showed that DEX can directly bind with PDK4.</p><p><strong>Conclusion: </strong>PDK4 can enhance the osteogenic differentiation ability of MSCs and bone mass of GIOP rats. DEX may promote the degradation of PDK4 via lysosome pathway, through which to weaken the osteogenic ability of MSCs by increasing ferroptosis. PDK4 may become a potential target for improving GIOP.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"91"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504266","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":"Effects of mesenchymal stem cells from different sources on the biological functions of multiple myeloma cells.","authors":"Yanju Li, Yang Liu, Xu Yang, Bo Yang, Jinyang Cheng, Juan Chen, Xiaoshuang Yuan, Xiao Xu, Guangyang Liu, Zhixu He, Feiqing Wang","doi":"10.1186/s13287-025-04222-8","DOIUrl":"10.1186/s13287-025-04222-8","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic benefits of mesenchymal stromal cells (MSCs) are largely dependent on paracrine factors, but the supernatants of the different MSCs may have different effects on multiple myeloma (MM) cells. Therefore, this study compared supernatants of bone marrow-derived mesenchymal stromal cells (BM-MSCs) with umbilical cord wharton's jelly's mesenchymal stem cells (UC-WJ MSCs) in different states (non-senescent and replicative senescence) on the MM cells.</p><p><strong>Methods: </strong>We extracted human BM-MSCs and UC-WJ MSCs in vitro and used H₂O₂ to induce replicative senescence. Concentrated supernatants from MSCs and senescent MSCs (SMSCs) were added to MM cells. Cell proliferation, the cell cycle, apoptosis, cell migration, tumor stemness factor expression, and cytokine expression levels were analyzed. Transcription regulation of signaling pathways was discussed.</p><p><strong>Results: </strong>We successfully isolated and identified BM-MSCs, UC-WJ MSCs, and SMSCs. When concentrated supernatants from BM-MSCs, UC-WJ MSCs, senescent BM-MSCs (SBM-MSCs), senescent UCWJ MSCs (SUC-WJ MSCs) were used to treat MM cells, BMMSCs and SBM-MSCs supernatants promoted the proliferation of MM cells, with a more pronounced effect by SBM-MSCs. UC-WJ MSCs and SUC-WJ MSCs supernatants inhibited the viability and proliferation of MM cells. BM-MSCs and SBM-MSCs supernatants increased the proportion of MM cells in the S-phase, with the effect of SBM-MSCs being more evident. UC-WJ MSCs and SUC-WJ MSCs supernatants arrested MM cells in the G0/G1 phase. BM-MSCs and SBM-MSCs supernatants enhanced the migration and tumor stemness of MM cells, with SBMMSCs having a more dramatic effect. UC-WJ MSCs and SUC-WJ MSCs supernatants inhibited the migration and tumor stemness of MM cells, with UC-WJ MSCs having a more inhibitory effect. IL-6 and VEGFA expression correlated negatively with the survival of patients with MM according to online database analysis, in addition, we found that the expression of IL-6 and VEGFA was higher in MM patients through GEO database analysis. BM-MSCs and SBM-MSCs supernatants treatment increased the expression of IL-6 and VEGFA on MM cells, while UC-WJ MSCs and SUC-WJ MSCs supernatants inhibited their expression. Signal pathway validation showed that the biological function of MSCs in MM is closely related to the PI3K/AKT/NF-κB pathway.</p><p><strong>Conclusion: </strong>The supernatants of BM-MSCs promote the proliferation of MM cells, On the contrary, the supernatants of UC-WJ MSCs inhibit MM cell proliferation. We observed that MSCs from different sources and different states have contrasting biological functions in MM cells. Furthermore, this research was provided to the optimal cancer gene therapy vector for MM was UC-WJ MSCs, even UC-WJ MSCs was in the state of senescence.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"89"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504123","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":"Fascia-derived stem cells enhance fat graft retention by promoting vascularization through the HMOX1-HIF-1α pathway.","authors":"Guo Chen, Jie Long, Yuge Zhang, Xuhua Zhou, Botao Gao, Zijin Qin, Yuhan Zhu, Binyu Song, Ziwei Cui, Zhangzi Liu, Man Xu, Zhou Yu, Baoqiang Song, Ziang Zhang","doi":"10.1186/s13287-025-04204-w","DOIUrl":"10.1186/s13287-025-04204-w","url":null,"abstract":"<p><strong>Background: </strong>Adipose tissue is a widely used autologous soft tissue filler in plastic surgery, particularly for volumetric restoration in cases of soft tissue deficiency. However, effectively controlling the retention rate of transplanted fat remains a major challenge. Therefore, this study aims to explore strategies to enhance fat graft retention. We isolated fascia-derived stem cells (FDSCs) from human superficial fascia and compared their gene expression profiles with those of adipose-derived stem cells (ADSCs). Through bioinformatics analysis and functional experiments, we identified significant differences in the angiogenic potential of the two cell types. Based on sequencing results, we further investigated the roles of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 (HMOX1). This study highlights the critical potential of FDSCs in improving fat graft retention and promoting angiogenesis, offering new strategies for enhancing graft survival and optimizing tissue regeneration therapies.</p><p><strong>Methods: </strong>We isolated fascia-derived stem cells (FDSCs) from human superficial fascia and compared them with adipose-derived stem cells (ADSCs). RNA sequencing was performed to analyze gene expression profiles, followed by bioinformatics analysis to identify differences in angiogenic potential. Functional experiments were conducted to investigate the roles of HIF-1α and HMOX1 in angiogenesis.</p><p><strong>Results: </strong>RNA sequencing revealed significant gene expression differences related to angiogenesis in FDSCs. The expression levels of HMOX1, HIF-1α, and VEGFa were significantly higher in FDSCs than in ADSCs, and HMOX1 positively regulated the expression of HIF-1α and VEGFa. In vitro experiments demonstrated that FDSCs promoted angiogenesis more effectively than ADSCs. In vivo co-transplantation experiments further confirmed that FDSCs improved fat graft retention and vascularization.</p><p><strong>Conclusions: </strong>We demonstrated that FDSCs can more effectively promote vascularization both in vitro and in vivo, and significantly improve graft retention, indicating their broad potential for future applications in tissue repair and regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"92"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504221","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":"Melatonin-pretreated mesenchymal stem cell-derived exosomes alleviate cavernous fibrosis in a rat model of nerve injury-induced erectile dysfunction via miR-145-5p/TGF-β/Smad axis.","authors":"Xiaolin Zhang, Mengbo Yang, Xinda Chen, Ming Zhang, Yiliang Peng, Mujun Lu","doi":"10.1186/s13287-025-04173-0","DOIUrl":"10.1186/s13287-025-04173-0","url":null,"abstract":"<p><strong>Background: </strong>Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common complication after radical prostatectomy. Conventional treatment approaches have had little success in treating the severe cavernous fibrosis which is a consequence of CNI-ED.</p><p><strong>Methods: </strong>Pre-treatment of adipose-derived stem cells with melatonin allows for the extraction of active exosomes (MT-hASC-EVs) from the conditioned medium. The therapeutic effects of MT-hASC-EVs were assessed in a rat model of CNI-ED, and the anti-fibrotic properties were evaluated. MicroRNA sequencing was used to identify specific microRNAs highly expressed in MT-hASC-EVs, and differential microRNAs were screened for regulatory pathways through target gene enrichment analysis. Finally, the conclusions from bioinformatics analysis were validated through in vitro experiments.</p><p><strong>Results: </strong>Intracavernous injection of MT-hASC-EVs significantly restored erectile function and reduced the extent of corpus cavernosum fibrosis in the CNI-ED rat model. MT-hASC-EVs promoted the proliferation and anti-apoptotic effects of corpus cavernosum smooth muscle cells (CCSMCs) in vitro. Mechanistically, MT-hASC-EVs inhibit fibrosis by delivering miR-145-5p, which targets TGF-β2/Smad3 axis.</p><p><strong>Conclusions: </strong>MT-hASCs-EVs can inhibit cavernous fibrosis and improve erectile function in a rat model of CNI-ED by targeting the miR-145-5p/TGF-β/Smad axis.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"96"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504263","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":"Progress of mesenchymal stem cells affecting extracellular matrix metabolism in the treatment of female stress urinary incontinence.","authors":"Chunyun Fang, Zitao Zeng, Junsong Ye, Bin Ni, Junrong Zou, Guoxi Zhang","doi":"10.1186/s13287-025-04220-w","DOIUrl":"10.1186/s13287-025-04220-w","url":null,"abstract":"<p><p>Stress urinary incontinence (SUI) is a prevalent pelvic floor dysfunction in women post-pregnancy. Currently, conservative treatment options have low success rates, while surgical interventions often result in multiple complications. The altered state of the extracellular matrix (ECM) is a pivotal factor in the onset of various diseases and likely plays a significant role in the pathogenesis of SUI, particularly through changes in collagen and elastin levels. Recent advances in mesenchymal stem cells (MSCs) therapy have shown considerable promise in treating SUI by modulating ECM remodeling, thereby enhancing the supportive tissues of the female pelvic floor. MSCs exhibit substantial potential in enhancing urethral sphincter function, modulating connective tissue architecture, and stimulating fibroblast activity. They play a pivotal role in the reconstruction and functional recovery of the ECM by influencing various signaling pathways, including TGF-β/SMAD, JAK/STAT, Wnt/β-catenin, PI3K/AKT, and ERK/MAPK. We have reviewed the advancements in MSC-mediated ECM metabolism in SUI and, by integrating the functions of ECM in other diseases and how MSCs can ameliorate conditions through their impact on ECM metabolism, we have projected the future trajectory of SUI treatment development.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"95"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504264","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":"Retinal ganglion cells induce stem cell-derived neuroprotection via IL-12 to SCGF-β crosstalk.","authors":"Qing Xia, Kun-Che Chang, Yanan Sun, Michael Nahmou, Takahiko Noro, Yun Cheng, Xiangmei Kong, Xiaofen Mo, Jeffrey L Goldberg, Suqian Wu","doi":"10.1186/s13287-025-04198-5","DOIUrl":"10.1186/s13287-025-04198-5","url":null,"abstract":"<p><strong>Background: </strong>Stem cell-derived secreted factors could protect neurons in neurodegenerative disease or after injury. The exact neuroprotective components in the secretome remain challenging to discover. Here we developed a cell-to-cell interaction model to identify a retinal ganglion cell (RGC)-protective factor derived from induced pluripotent stem cells (iPSCs).</p><p><strong>Methods: </strong>Primary RGCs were co-cultured with iPSCs or treated with iPSC-conditioned media in vitro. Cell viability were assayed using live-cell staining, and culture supernatant were analyzed via multiplexed antibody-based assays and ELISA. In vivo tests were carried out under mouse optic nerve crush model and RGC transplantation study in rats. Paired t-tests were used for data analysis between two groups.</p><p><strong>Results: </strong>RGC viability was significantly enhanced when iPSCs were first stimulated with RGC-derived supernatant before iPSC-conditioned medium was collected and added into RGC culture. A significant increase of stem cell growth factor-beta (SCGF-β) concentration was detected in the latter conditioned medium. SCGF-β enhanced RGC survival in vitro and in vivo, and RGC-derived interleukin-12(p70) (IL-12[p70]) promotes secretion of iPSC-derived SCGF-β. Downstream of this IL-12(p70)-to-SCGF-β axis, ngn2 was significantly upregulated, and was found both necessary and sufficient for RGC survival.</p><p><strong>Conclusion: </strong>This study addresses a longstanding question of how neurons and stem cells interact to promote neuroprotection, and define a novel molecular interaction pathway whereby RGC's secretion of IL-12(p70) enhances iPSCs' secretion of SCGF-β, and SCGF-β protects RGCs via upregulating ngn2, suggesting that neurons may call on stem cells for their own protection.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"90"},"PeriodicalIF":7.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504270","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":"Circadian rhythms in stem cells and their therapeutic potential.","authors":"Napasiri Putthanbut, Paul Alexis Bourgade Su, Jea-Young Lee, Cesario V Borlongan","doi":"10.1186/s13287-025-04178-9","DOIUrl":"10.1186/s13287-025-04178-9","url":null,"abstract":"<p><p>Circadian rhythms are present in almost all cells, but their existence in stem cells has remains not well established. Circadian clock appears to be closely associated with differentiated mature cells and rarely detected in immature embryonic stem cells. Recent evidence reveals the presence of circadian genes and rhythmic physiologic activities in stem cells as well as stem cell-derived extracellular vesicle (EV) characteristics. The circadian clock entails diverse physiologic and pathological mechanisms underlying cell fate. Integration of circadian rhythm to clinical applications, such as chronotherapy, chrono-biomarker, and environment modification, may facilitate therapeutic outcomes of stem cell-based regenerative medicine. Understanding circadian rhythms in stem cells can optimize stem cell-based therapies by determining the best times for harvesting and administering stem cells, thereby enhancing therapeutic efficacy. Further research into the circadian properties of stem cells will refine stem cell-based therapies, contributing to advancements in regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"85"},"PeriodicalIF":7.1,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483975","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}