Stem Cell Research & Therapy最新文献

{"title":"Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons.","authors":"Yu Pan, Haohui Lin, Manhon Chung, Yi Yang, Li Zhang, Xiaohua Pan, Sa Cai","doi":"10.1186/s13287-025-04217-5","DOIUrl":"10.1186/s13287-025-04217-5","url":null,"abstract":"<p><strong>Background: </strong>Phenotypically unstable Schwann cell-like cells (SCLCs), derived from mesenchymal stem cells (MSCs) require intercellular contact-mediated cues for Schwann cell (SCs)-fate commitment. Although rat dorsal root ganglion (DRG) neurons provide contact-mediated signals for the conversion of SCLCs into fate-committed SCs, the use of animal cells is clinically unacceptable. To overcome this problem, we previously acquired human induced pluripotent stem cell-derived sensory neurons (hiPSC-dSNs) as surrogates of rat DRG neurons that committed rat bone marrow SCLCs to the SC fate. In this study, we explored whether hiPSC-dSNs could mimic rat DRG neuron effects to obtain fate-committed SCs from hBMSC-derived SCLCs.</p><p><strong>Methods: </strong>hiPSCs were induced into hiPSC-dSNs using a specific chemical small molecule combination. hBMSCs were induced into hBMSC-derived SCLCs in a specific culture medium and then co-cultured with hiPSC-dSNs to generate SCs. The identity of hBMSC-derived SCs (hBMSC-dSCs) was examined by immunofluorescence, western bolt, electronic microscopy, and RNA-seq. Immunofluorescence was also used to detect the myelination capacity. Enzyme-linked immunosorbent assay and neurite outgrowth analysis were used to test the secretion of neurotrophic factors.</p><p><strong>Results: </strong>The hBMSC-dSCs exhibited bi-/tri-polar morphology of SCs and maintained the expression of the SC markers S100, p75NTR, p0, GFAP, and Sox10, even after withdrawing the glia-inducing factors or hiPSC-dSNs. Electronic microscopy and RNA-seq analysis provided evidence that hBMSC-dSCs were similar to the original human SCs in terms of their function and a variety of characteristics. Furthermore, these cells formed MBP-positive segments and secreted neurotrophic factors to facilitate the neurite outgrowth of Neuro2A.</p><p><strong>Conclusions: </strong>These results demonstrated that phenotypically stable and functionally mature hBMSC-dSCs were generated efficiently via the co-culture of hiPSC-dSNs and hBMSC-derived SCLCs. Our findings may provide a promising protocol through which stable and fully developed hBMSC-dSCs can be used for transplantation to regenerate myelin sheath.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"106"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537683","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":"The role of oxidative stress-mediated fibro-adipogenic progenitor senescence in skeletal muscle regeneration and repair.","authors":"Yuqing Yao, Yusheng Luo, Xiaomei Liang, Li Zhong, Yannan Wang, Zhengchao Hong, Chao Song, Zeyu Xu, Jiancheng Wang, Miao Zhang","doi":"10.1186/s13287-025-04242-4","DOIUrl":"10.1186/s13287-025-04242-4","url":null,"abstract":"<p><strong>Background: </strong>Stem cells play a pivotal role in tissue regeneration and repair. Skeletal muscle comprises two main stem cells: muscle stem cells (MuSCs) and fibro-adipogenic progenitors (FAPs). FAPs are essential for maintaining the regenerative milieu of muscle tissue and modulating the activation of muscle satellite cells. However, during acute skeletal muscle injury, the alterations and mechanisms of action of FAPs remain unclear.</p><p><strong>Methods: </strong>we employed the GEO database for bioinformatics analysis of skeletal muscle injury. A skeletal muscle injury model was established through cardiotoxin (CTX, 10µM, 50µL) injection into the tibialis anterior (TA) of C57BL/6 mice. Three days post-injury, we extracted the TA, isolated FAPs (CD31^-CD45^-PDGFRα⁺Sca-1⁺), and assessed the senescence phenotype through SA-β-Gal staining and Western blot. Additionally, we established a co-culture system to evaluate the capacity of FAPs to facilitate MuSCs differentiation. Finally, we alleviated the senescent of FAPs through in vitro (100 µM melatonin, 5 days) and in vivo (20 mg/kg/day melatonin, 15 days) administration experiments, confirming melatonin's pivotal role in the regeneration and repair processes of skeletal muscle.</p><p><strong>Results: </strong>In single-cell RNA sequencing analysis, we discovered the upregulation of senescence-related pathways in FAPs following injury. Immunofluorescence staining revealed the co-localization of FAPs and senescent markers in injured muscles. We established the CTX injury model and observed a reduction in the number of FAPs post-injury, accompanied by the manifestation of a senescent phenotype. Melatonin treatment was found to attenuate the injury-induced senescence of FAPs. Further co-culture experiments revealed that melatonin facilitated the restoration of FAPs' capacity to promote myoblast differentiation. Through GO and KEGG analysis, we found that the administration of melatonin led to the upregulation of AMPK pathway in FAPs, a pathway associated with antioxidant stress response. Finally, drug administration experiments corroborated that melatonin enhances skeletal muscle regeneration and repair by alleviating FAP senescence in vivo.</p><p><strong>Conclusion: </strong>In this study, we first found FAPs underwent senescence and redox homeostasis imbalance after injury. Next, we utilized melatonin to enhance FAPs regenerative and repair capabilities by activating AMPK signaling pathway. Taken together, this work provides a novel theoretical foundation for treating skeletal muscle injury.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"104"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537706","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":"Mesenchymal stem cells alleviate idiopathic pneumonia syndrome by facilitating M2 polarization via CCL2/CCR2 axis and further inducing formation of regulatory CCR2 + CD4 + T cells.","authors":"Chao Xue, Wei Liu, Yuan Li, Yue Yin, Bo Tang, Jinye Zhu, Yujun Dong, Huihui Liu, Hanyun Ren","doi":"10.1186/s13287-025-04232-6","DOIUrl":"10.1186/s13287-025-04232-6","url":null,"abstract":"<p><strong>Background: </strong>Our previous study revealed that mesenchymal stem cells (MSCs) can secrete large amounts of the chemokine CCL2 under inflammatory conditions and alleviate idiopathic pneumonia syndrome (IPS) by promoting regulatory CCR2 + CD4 + T-cell formation through the CCL2‒CCR2 axis. Given the abundance of macrophages in lung tissue, how these macrophages are regulated by MSC-based prophylaxis via IPS and their interactions with T cells in lung tissue during allo-HSCT are still not fully understood.</p><p><strong>Methods: </strong>An IPS mouse model was established, and MSC-based prophylaxis was administered. In vitro coculture systems and an IPS model were used to study the interactions among MSCs, macrophages and T cells.</p><p><strong>Results: </strong>Prophylactic administration of MSCs induced M2 polarization and alleviated acute graft-versus-host disease (aGVHD) and lung injury in an IPS mouse model. In vitro coculture studies revealed that M2 polarization was induced by MSC-released CCL2 and that these M2 macrophages promoted the formation of regulatory CCR2 + CD4 + T cells. Blocking the CCL2-CCR2 interaction in vitro reversed MSC-induced M2 polarization and abolished the induction of CCR2 + CD4 + T-cell formation. Additionally, in vivo administration of a CCL2 or CCR2 antagonist in the IPS mouse model exacerbated aGVHD and lung injury, accompanied by a reduction in M2 macrophages and reduced formation of regulatory CCR2 + CD4 + T cells in lung tissue.</p><p><strong>Conclusions: </strong>MSCs alleviate IPS by facilitating M2 polarization via the CCL2‒CCR2 axis and further inducing the formation of regulatory CCR2 + CD4 + T cells.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"108"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537691","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":"Inhibition of circALPK2 enhances proliferation and therapeutic potential of human pluripotent stem cell-derived cardiomyocytes in myocardial infarction.","authors":"Hongchun Wu, Xue Jiang, Hao Fan, Jingjing Li, Yuan Li, Yingjiong Lin, Dandan Zhao, Xinglong Han, Miao Yu, Jun-Ming Tang, Shijun Hu, Wei Lei","doi":"10.1186/s13287-025-04230-8","DOIUrl":"10.1186/s13287-025-04230-8","url":null,"abstract":"<p><strong>Background: </strong>Understanding the mechanisms regulating human cardiomyocyte proliferation holds significant promise for developing effective therapies to enhance cardiac regeneration and repair. This study investigates the role of circALPK2, a circular RNA derived from the back-splicing of the 4th exon of alpha protein kinase 2 (ALPK2), in regulating cardiomyocyte proliferation and its therapeutic efficacy in myocardial infarction (MI) treatment.</p><p><strong>Methods: </strong>Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were used to assess the expression and function ofcircALPK2. Lentiviral shRNA-mediated knockdown of circALPK2 was performed in hESC-CMs, followed by RNA sequencing to identify targeted genes and biological processes. The proliferative capacity of wild-type and circALPK2 knockdown hESC-CMs was evaluated using CCK-8 assay, EdU staining and RT-qPCR analysis of cell cycle-related genes. Dual luciferase assays were conducted to validate the predicted miRNA targets and their downstream effects. For in vivo evaluation, MI mice were injected with either wild-type or circALPK2 knockdown hESC-CMs, and the therapeutic potential was assessed by echocardiographic and histological analyses.</p><p><strong>Results: </strong>We identified circALPK2 as a negative regulator of cell proliferation in hESC-CMs. CircALPK2 was abundantly expressed in hESC-CMs. Knockdown of circALPK2 significantly enhanced cell proliferation in hESC-CMs, as demonstrated by CCK-8 assays (p < 0.001) and EdU staining (p < 0.001), and accelerated the expression of cell cycle-related genes, including CCNA2(p < 0.05) and CDK1 (p < 0.01). Furthermore, circALPK2 was found to function as a sponge to inhibit miR-9 activity, while miR-9 mimics significantly boosted the proliferative capacity of hESC-CMs. Glycogen synthase kinase 3β (GSK3B), a key inhibitor of WNT signaling, was identified as a direct target of miR-9, mediating the regulation of cardiomyocyte proliferation. Importantly, circALPK2 knockdown improved the myocardial repair potential of hESC-CMs when injected into infarcted mouse hearts, as indicated by improved left ventricular ejection fraction (p < 0.01) and fractional shortening (p < 0.05).</p><p><strong>Conclusions: </strong>Our study identifies the circALPK2/miR-9/GSK3B axis as a novel target for promoting cardiomyocyte proliferation and enhancing cardiac regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"107"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537688","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":"Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway.","authors":"Miao Dong, Xuan Ma, Facheng Li","doi":"10.1186/s13287-025-04205-9","DOIUrl":"10.1186/s13287-025-04205-9","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers pose significant challenges for clinicians worldwide. Cell-free exosome therapy holds great potential for wound healing. Dedifferentiated fat cells (DFATs) have been used in tissue engineering and regeneration, but there are no reports on the use of DFATs-derived exosomes in diabetic wound repair.</p><p><strong>Objectives: </strong>This study aims to investigate whether DFATs-Exos accelerated diabetic wound healing and explore its potential mechanism.</p><p><strong>Methods: </strong>In vitro, DFATs-Exos were harvested from adipose tissue and used to treat endothelial cells (ECs) and fibroblasts. XAV939 was used as a Wnt/β-catenin pathway inhibitor. The biocompatibility of gelatin methacryloyl (GelMA) hydrogel was assessed. In vivo, DFAT-derived exosomes were encapsulated in 10% GelMA hydrogel and applied to a diabetic wound model. Histological analysis and wound closure rates were evaluated.</p><p><strong>Results: </strong>DFATs-Exos promoted angiogenesis in ECs and significantly alleviated the high glucose-induced inhibition of cell proliferation and migration by activating the Wnt/β-catenin pathway. In vivo, compared to DFAT-Exos or GelMA alone, the DFAT-Exos/GelMA combination accelerated wound closure and enhanced collagen maturity.</p><p><strong>Conclusion: </strong>The DFAT-Exos/GelMA hydrogel significantly promoted wound healing in a diabetic animal model through activation of the Wnt/β-catenin signaling pathway.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"103"},"PeriodicalIF":7.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531809","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":"Ultrasound-guided renal subcapsular transplantation of mesenchymal stem cells for treatment of acute kidney injury in a minipig model: safety and efficacy evaluation.","authors":"Tuo Xiao, Yuhao Chen, Bo Jiang, Mengjie Huang, Yanjun Liang, Yue Xu, Xumin Zheng, Wenjuan Wang, Xiangmei Chen, Guangyan Cai","doi":"10.1186/s13287-025-04137-4","DOIUrl":"10.1186/s13287-025-04137-4","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a major global public health concern with limited treatment options. While preclinical studies have suggested the potential of mesenchymal stem cells (MSCs) to repair and protect injured kidneys in AKI, clinical trials using transarterial MSCs transplantation have yielded disappointing results. This study aimed to investigate the feasibility and safety of minimally invasive renal subcapsular transplantation of MSCs for treating AKI in a minipig model, ultimately aiming to facilitate the clinical translation of this approach.</p><p><strong>Methods: </strong>A novel AKI minipig model was established by combining cisplatin with hydration to evaluate the effectiveness of potential therapies. Renal subcapsular catheterization was successfully achieved under ultrasound guidance. Subsequently, the efficacy of renal subcapsular MSCs transplantation was assessed, and the biological role of the tryptophan metabolite kynurenine (Kyn) in AKI was elucidated through both in vivo and in vitro experiments.</p><p><strong>Results: </strong>The method of pre-hydration at 4% of body weight, followed by post-cisplatin (3.8 mg/kg) hydration at 2% of body weight, successfully established a cisplatin-induced AKI minipig model with a survival time exceeding 28 days, closely mimicking the clinical characteristics of typical AKI patients. Additionally, we discovered that multiple MSCs transplantations promoted renal function recovery more effectively than single transplantation via the renal subcapsular catheter. Furthermore, elevated levels of Kyn were observed in kidney during AKI, which activated the aryl hydrocarbon receptor (AhR)-mediated NF-κB/NLRP3/IL-1β signaling pathway in tubular epithelial cells, thereby exacerbating inflammatory injury.</p><p><strong>Conclusions: </strong>Ultrasound-guided renal subcapsular transplantation of mesenchymal stem cells is a safe and effective therapeutic approach for AKI, with the potential to bring about significant clinical advancements in the future.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"102"},"PeriodicalIF":7.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531788","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":"Donor age and breed determine mesenchymal stromal cell characteristics.","authors":"Emma Heyman, Maria Olenic, Elly De Vlieghere, Stefaan De Smet, Bert Devriendt, Lieven Thorrez, Catharina De Schauwer","doi":"10.1186/s13287-025-04236-2","DOIUrl":"10.1186/s13287-025-04236-2","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stromal cells (MSCs) hold significant potential for various applications in regenerative medicine and tissue engineering. Initially considered as a single cell type with defined characteristics, MSCs are now known as a heterogeneous cell population with remarkable differences in their properties. No consensus exists on how donor age affects MSC characteristics, like proliferation. Additionally, differences in differentiation capacities and immunophenotype could arise when MSCs are isolated from different animals breeds, which is relevant for experimental and preclinical studies of MSC-based treatments.</p><p><strong>Methods: </strong>In this study, we isolated bovine adipose tissue-derived MSCs from three age categories, i.e. fetal, calf, and adult, and of two different breeds, i.e. Holstein Friesian (HF) and Belgian Blue (BB). MSC characterization included tri-lineage differentiation, proliferation and senescence assays, and immunophenotyping using multi-color flow cytometry.</p><p><strong>Results: </strong>Especially fetal and calf HF-MSCs showed a high proliferation capacity, where 4 and 6 out of 7 donors, respectively, could surpass 30 population doublings. Adipogenic differentiation potential was higher for fetal and adult HF-MSCs. Furthermore, breed, but not age, affected their osteogenic differentiation potential, with BB-MSCs performing better. Evaluation of cell surface marker expression revealed a breed effect, as calf HF-MSCs showed a higher percentage of Cluster of Differentiation (CD)34⁺ cells compared to calf BB-MSCs, which was correlated with both osteogenic differentiation and proliferation potential.</p><p><strong>Conclusions: </strong>Our findings clearly show the impact of donor characteristics such as age and breed on MSC proliferation, immunophenotype, and differentiation potential, illustrating the importance of selecting the appropriate MSC donor for MSC-based treatments when allogeneic MSCs are considered.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"99"},"PeriodicalIF":7.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531811","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":"Thrombin-preconditioned mesenchymal stromal cell-derived extracellular vesicles attenuate experimental necrotizing enterocolitis.","authors":"Sein Hwang, Se In Sung, Young Eun Kim, Misun Yang, Ara Koh, So Yoon Ahn, Yun Sil Chang","doi":"10.1186/s13287-025-04243-3","DOIUrl":"10.1186/s13287-025-04243-3","url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a critical gastrointestinal disease in preterm infants, for which no specific treatment is established. We previously demonstrated that thrombin-preconditioned mesenchymal stromal cell-derived extracellular vesicles (thMSC-EVs) enhance protection against other neonatal tissue injuries. Therefore, this study aimed to evaluate the therapeutic potential of thMSC-EVs in modified in vitro, in vivo, and organoid models of NEC.</p><p><strong>Methods: </strong>In vitro, the effects of thMSC-EVs and naïveMSC-EVs were compared in hyperosmotic, ischemic, and hypothermic (HIT)-stressed IEC-6 cells and LPS-treated peritoneal macrophages. In vivo, NEC was induced in P4 mouse pups by three cycles of formula feeding, oral LPS administration, hypoxia, and hypothermia, followed by overnight dam care. 2 × 10⁹ thMSC-EVs were intraperitoneally administered daily for three days, and the therapeutic effects were assessed macroscopically, histologically, and biochemically. NEC mouse-derived organoids were established to evaluate the thMSC-EVs' effect in mature enterocytes. LC-MS/MS was performed to analyze the EV proteomics.</p><p><strong>Results: </strong>In vitro, compared with naïveMSC-EVs, thMSC-EVs significantly improved cellular viability in HIT-induced IEC-6 cells and reduced pro-inflammatory (IL-1α, IL-1β, TNF-α) but increased anti-inflammatory (TGF-b) cytokine levels in LPS-treated peritoneal macrophages. In vivo, thMSC-EVs significantly attenuated clinical symptoms, reduced intestinal damage, and retained intestinal stem cell markers, showing more significant localization in NEC-induced intestines than in healthy intestines. In NEC mouse-derived organoids, thMSC-EVs significantly increased OLFM4 and claudin-4 expression and reduced stress-related markers such as sucrase-isomaltase, defensin, and chromogranin A. Proteomic analysis revealed that thMSC-EVs were greater enriched in anti-apoptotic, anti-inflammatory, cell adhesion, and Wnt signaling pathways than naïveMSC-EVs.</p><p><strong>Conclusion: </strong>thMSC-EVs improved cellular viability, reduced apoptosis, attenuated inflammation, and upregulated key intestinal stem cell markers, collectively suggesting their tissue-protective effects and highlighting their potential as a treatment for NEC.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"101"},"PeriodicalIF":7.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531759","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":"Mesenchymal stem cells overexpressing neuropeptide S promote the recovery of rats with spinal cord injury by activating the PI3K/AKT/GSK3β signaling pathway.","authors":"Wenhui Yang, Yilu Li, Yushi Tang, Zhenxing Tao, Mengyuan Yu, Cuiping Sun, Yang Ye, Bai Xu, Xudong Zhao, Yazhuo Zhang, Xiaojie Lu","doi":"10.1186/s13287-025-04250-4","DOIUrl":"10.1186/s13287-025-04250-4","url":null,"abstract":"<p><strong>Background: </strong>Transplantation of nasal mucosa-derived mesenchymal stem cells (EMSCs) overexpressing neuropeptide S (NPS) is a promising approach for treating spinal cord injury (SCI). Despite the potential of stem cell therapy, challenges remain regarding cell survival and differentiation control. We aimed to conduct orthotopic transplantation of transected spinal cord to treat rats with complete SCI.</p><p><strong>Methods: </strong>In this study, we loaded NPS-overexpressing EMSCs onto hydrogels to enhance cell survival in vivo and promote neuronal differentiation both in vitro and in vivo. However, in vitro co-culture promoted greater neuronal differentiation of neural stem cells (P < 0.01). When transplanted in vivo, NPS-overexpressing EMSCs showed greater cell survival in the transplanted area compared with stem cells without gene modification within 4 weeks after spinal cord implantation in rats (P < 0.01).</p><p><strong>Results: </strong>Compared with those in the other groups, stable overexpression of NPS-EMSCs in a rat model with SCI significantly improved the treatment effect, reduced glial scar formation, promoted neural regeneration and endogenous neural stem cell proliferation and differentiation into neurons, and improved motor function.</p><p><strong>Conclusions: </strong>These results indicate that this effect may be achieved by the overexpression of NPS-EMSCs through the activation of the PI3K/Akt/GSK3β signaling pathway. Overall, the overexpression of EMSCs significantly improved the therapeutic effect of SCI in rats, strongly supporting the potential for gene modification of mesenchymal stem cells in clinical applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"100"},"PeriodicalIF":7.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531758","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":"The promise of mesenchymal stromal/stem cells in erectile dysfunction treatment: a review of current insights and future directions.","authors":"Ayyub Ali Patel, Alaa Shafie, Asma'a H Mohamed, Sana Abdul-Jabbar Ali, Faris J Tayeb, Hisham Ali Waggiallah, Irfan Ahmad, Salah Ahmed Sheweita, Khursheed Muzammil, Abdullah M AlShahrani, Waleed Al Abdulmonem","doi":"10.1186/s13287-025-04221-9","DOIUrl":"10.1186/s13287-025-04221-9","url":null,"abstract":"<p><p>Erectile dysfunction is a common and multifactorial condition that significantly impacts men's quality of life. Traditional treatments, such as phosphodiesterase type 5 inhibitors (PDE5i), often fail to provide lasting benefits, particularly in patients with underlying health conditions. In recent years, regenerative medicine, particularly stem cell therapies, has emerged as a promising alternative for managing erectile dysfunction. This review explores the potential of mesenchymal stromal/stem cells (MSCs) and their paracrine effects, including extracellular vesicles (EVs), in the treatment of erectile dysfunction. MSCs have shown remarkable potential in promoting tissue repair, reducing inflammation, and regenerating smooth muscle cells, offering therapeutic benefits in models of erectile dysfunction. Clinical trials have demonstrated positive outcomes in improving erectile function and other clinical parameters. This review highlights the promise of MSC therapy for erectile dysfunction, discusses existing challenges, and emphasizes the need for continued research to refine these therapies and improve long-term patient outcomes.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"98"},"PeriodicalIF":7.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516745","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}