Stem Cell Research & Therapy最新文献

{"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}

{"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}