Stem Cell Research & Therapy最新文献

{"title":"DMSO-free cryopreservation of hiPSC-derived cardiomyocytes: low temperature characterization and protocol development.","authors":"Akshat S Mallya, Tessa Burrows, Jeanne Hsieh, Troy Louwagie, James R Dutton, Brenda M Ogle, Allison Hubel","doi":"10.1186/s13287-025-04384-5","DOIUrl":"10.1186/s13287-025-04384-5","url":null,"abstract":"<p><strong>Background: </strong>Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have attracted significant interest for use in disease modeling, drug discovery and potential therapeutic applications. However, conventional hiPSC-CM cryopreservation protocols largely use dimethyl sulfoxide (DMSO) as the cryoprotectant (CPA), which is linked with a loss of post-thaw recovery and function for various cell types and is not ideal for therapeutic protocols. Additionally, the effect of freezing parameters such as cooling rate and nucleation temperature on post-thaw recovery of hiPSC-CMs has not been explored.</p><p><strong>Methods: </strong>hiPSC-CMs were generated by Wnt pathway inhibition, followed by sodium l-lactate purification. Subsequently, biophysical characterization of the cells was performed. A differential evolution (DE) algorithm was utilized to determine the optimal composition of a mixture of a sugar, sugar alcohol and amino acid to replace DMSO as the CPA. The hiPSC-CMs were subjected to controlled-rate freezing at different cooling rates and nucleation temperatures. The optimum freezing parameters were identified by post-thaw recoveries and the partitioning ratio obtained from low temperature Raman spectroscopy studies. The post-thaw osmotic behavior of hiPSC-CMs was studied by measuring diameter of cells resuspended in the isotonic culture medium over time. Immunocytochemistry and calcium transient studies were performed to evaluate post-thaw function.</p><p><strong>Results: </strong>hiPSC-CMs were found to be slightly larger than hiPSCs and exhibited a large osmotically inactive volume. The best-performing DMSO-free solutions enabled post-thaw recoveries over 90%, which was significantly greater than DMSO (69.4 ± 6.4%). A rapid cooling rate of 5 °C/min and a low nucleation temperature of -8 °C was found to be optimal for hiPSC-CMs. hiPSC-CMs displayed anomalous osmotic behavior post-thaw, dropping sharply in volume after resuspension. Post-thaw function was preserved when hiPSC-CMs were frozen with the best-performing DMSO-free CPA or DMSO and the cells displayed similar cardiac markers pre-freeze and post-thaw.</p><p><strong>Conclusions: </strong>It was shown that a CPA cocktail of naturally-occurring osmolytes could effectively replace DMSO for preserving hiPSC-CMs while preserving morphology and function. Understanding the anomalous osmotic behavior and managing the excessive dehydration of hiPSC-CMs could be crucial to improve post-thaw outcomes. Effective DMSO-free cryopreservation would accelerate the development of drug discovery and therapeutic applications of hiPSC-CMs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"301"},"PeriodicalIF":7.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267155","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":"Cell-derived exosome therapy for diabetic peripheral neuropathy: a preclinical animal studies systematic review and meta-analysis.","authors":"Xianying Lu, Ran Xu, Xiaohui Dong, Dingxi Bai, Wenting Ji, Xinyu Chen, Huan Chen, Chaoming Hou, Jing Gao","doi":"10.1186/s13287-025-04432-0","DOIUrl":"10.1186/s13287-025-04432-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Backgrounds: &lt;/strong&gt;Exosomes is a promising cell-free therapy for Diabetic peripheral neuropathy (DPN) that imposes long-term negative effects on patients' finances, mental health, and quality of life. We conducted a meta-analysis to assess the therapeutic effects of exosomes (such as SCs-derived, FCs-derived, BMSCs-derived, MSCs-derived, and Plasma-derived) on DPN.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched nine databases from inception to February 2025, then two researchers independently screened studies, extracted data, and assessed the quality of included studies using SYRCLE's tool. The outcome indicators consisted of at least one of the three key DPN endpoints (electrophysiology, behavioural assessment, and nerve structure) based on the Neurodiab guidelines. R 4.4.2 software was used to conduct all statistical analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;11 studies were identified, and the risk of bias in most studies was unclear generally. Pooled analyses demonstrated that exosome improved the nerve conduction velocity [MCV (SMD = 4.71 [2.18;7.25], P = 0.0003; I²= 91.8%), SCV (SMD = 1.07 [0.30;1.85], P = 0.0069; I²= 85.3%)], may restore IENFD [SMD = 1.46 [-0.85; 3.77], P = 0.2164; I²=88.7%], alleviated neuropathic pain [mechanical allodynia (SMD= -0.27 [-1.02;0.47], P = 0.4697; I&lt;sup&gt;2&lt;/sup&gt; = 85.0%), thermal hyperalgesia (SMD= -1.48 [-2.45;-0.50], P = 0.003; I&lt;sup&gt;2&lt;/sup&gt; = 88.4%)], ameliorated vascular function [blood flow perfusion in plantar (SMD = 2.84 [0.89; 4.80], P = 0.0043; I&lt;sup&gt;2&lt;/sup&gt; = 74.9%), blood flow perfusion in sciatic nerves (SMD = 2.62 [0.80; 4.43], P = 0.0047; I&lt;sup&gt;2&lt;/sup&gt; = 75.9%), vessel density (SMD = 2.69 [0.90; 4.49], P = 0.0032; I&lt;sup&gt;2&lt;/sup&gt; = 0%)], and restored the peripheral nerve structure [sciatic nerve fiber diameter (SMD = 3.29 [1.61; 4.96], P = 0.0066; I&lt;sup&gt;2&lt;/sup&gt; = 75.5%), axon diameter (SMD = 2.26 [1.64; 2.88], P &lt; 0.0001; I&lt;sup&gt;2&lt;/sup&gt; = 54.3%), myelin sheath thickness (SMD = 2.56 [1.39; 3.72], P &lt; 0.0001; I&lt;sup&gt;2&lt;/sup&gt; = 73.0%), g-ratio (SMD= -1.64 [-3.28; 0.00], P = 0.0502; I&lt;sup&gt;2&lt;/sup&gt; = 34.17)]. Furthermore, after exosome therapy, the expressions of NF-200 (SMD = 2.57 [0.39; 4.75], P = 0.0210; I&lt;sup&gt;2&lt;/sup&gt; = 33.0%), MBP (SMD = 2.27 [-1.49; 6.02], P = 0.1064; I&lt;sup&gt;2&lt;/sup&gt; = 59.0%), and S-100β (SMD = 1.90 [0.09; 3.72], P = 0.0399; I&lt;sup&gt;2&lt;/sup&gt; = 32.5%) evaluating axonal regeneration and remyelination increased significantly. Notably, high-glucose pretreatment of exosomes significantly attenuated these effects, while genetic overexpression modifications or novel dressings-mediated delivery partially counteracted this suppression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Exosome therapy provides a novel therapeutic strategy for the benefit of neurovascular remodeling and functional recovery of DPN, especially when used in conjunction with exosome modification and novel dressings. To bridge the translational gap between preclinical and clinical studies, future research should conduct more ","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"297"},"PeriodicalIF":7.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258934","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":"Let-7a-5p derived from parathyroid hormone (1-34)-preconditioned BMSCs exosomes delays the progression of osteoarthritis by promoting chondrocyte proliferation and migration.","authors":"Litao Shao, Lu Ding, Weizhao Li, Chi Zhang, Yu Xia, Miaoyu Zeng, Zhizhong Ye, David Y B Deng","doi":"10.1186/s13287-025-04416-0","DOIUrl":"10.1186/s13287-025-04416-0","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a prevalent degenerative joint disorder affecting over 240 million people worldwide, yet no disease-modifying therapies currently exist, with clinical management limited to symptomatic relief or joint replacement. Exosomes (Exos) from bone marrow mesenchymal stem cells (Exo^BMSC) play positive role in the treatment of cartilage damage. Parathyroid hormone (PTH) (1-34) can enhance cartilage repair. Here, We found Exos from Exo^BMSC reduces cartilage damage during treatment. Meanwhile, the Exos of PTH(1-34)-preconditioned BMSCs (Exo^PTH) can alleviate OA better than Exo^BMSC. Through MicroRNA (miRNA) sequencing analysis, this study aims to reveal the effects and potential mechanism of miRNA (let-7a-5p) in Exo^PTH to repair OA cartilage.</p><p><strong>Methods: </strong>Differential centrifugation was used for isolating Exo^BMSC and Exo^PTH. Extract bone marrow mesenchymal stem cells from rats and utilize the C28/I2 chondrocytes line, the OA model was established using lipopolysaccharide (LPS; 1 µg/mL) in vitro. OA was induced in rats with intra-articular injection with collagenase-2. By performing a miRNA array, RNA-seq, in addition to bioinformatic analysis, the miRNA and the potential regulatory mechanism were detected. We compared in vitro let-7a-5p effects on the ability of OA chondrocytes to proliferate, migrate, apoptosis, and form the extracellular matrix (ECM). Histological and immunohistochemical assessments were used for evaluating cartilage pathology in vivo.</p><p><strong>Results: </strong>We extracted Exo^BMSC and Exo^PTH and established the OA model in vitro. Compared with Exo^BMSC group, Exo^PTH group has a stronger effect on promoting the proliferation and migration of chondrocytes. Exo^BMSC and Exo^PTH can inhibit the apoptosis of chondrocytes, but there was no significant difference between the two groups. The two most significant differences in groups Exo^BMSC and Exo^PTH are let-7a-5p. Let-7a-5p promotes OA chondrocytes proliferation and migration by inhibiting the expression of IL-6 in vitro experiments. For in vivo experiments, let-7a-5p delays the progression of OA.</p><p><strong>Conclusion: </strong>Our study shows that Exo^PTH may improve the regulatory inflammatory responses to delays the progression of OA by shuttling let-7a-5p. Let-7a-5p promoted chondrocytes migration and proliferation to suppress OA pathology by inhibiting IL-6/STAT3 pathway.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"299"},"PeriodicalIF":7.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258935","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":"Repurposing of an inotropic drug dobutamine to enhance the production of human hematopoietic stem cells from human induced pluripotent stem cells.","authors":"Chuti Laowtammathron, Pimonwan Srisook, Pakpoom Kheolamai, Rangsun Parnpai, Chanchao Lorthongpanich, Surapol Issaragrisil","doi":"10.1186/s13287-025-04427-x","DOIUrl":"10.1186/s13287-025-04427-x","url":null,"abstract":"<p><strong>Background: </strong>Dobutamine hydrochloride (DH), a common inotropic drug used for heart failure, has recently been discovered to inhibit Yes-Associated Protein (YAP). YAP is a key component of the Hippo signaling pathway and plays a crucial role in the regulation of hematopoietic cell growth. The decrease in YAP activity has been shown to increase hematogenic differentiation and the generation of hematopoietic stem and progenitor cells (HSPCs) from human induced pluripotent stem cells (hiPSCs). Therefore, this study investigates the effect of DH on enhancing the hematopoietic differentiation of hiPSCs toward HSPCs.</p><p><strong>Methods: </strong>This study used isogenic hiPSCs to study the effect of DH during various stages of their hematogenic differentiation using an in vitro culture system. The differentiating hiPSCs were cultured under specific conditions, including defined differentiation media composition and controlled oxygen tension throughout the differentiation process. The percentages of iPSC-derived HSPCs were assessed using flow cytometry to evaluate the expression of HSPC markers, including CD34⁺, CD43⁺, and CD45⁺/⁻. The HSPC production yield and the multilineage differentiation capacity of the resulting hiPSC-derived HSPCs were determined at the end of culture.</p><p><strong>Results: </strong>The findings indicate that DH treatment significantly inhibits YAP activity and increases the hematogenic differentiation of hiPSCs and the yield of HSPCs at the end of culture. Specifically, inhibiting YAP activity with DH during the transition of hiPSCs from the hematoendothelial progenitor (HE) stage to the hematopoietic stage (endothelial to hematopoietic transition, EHT) proved to be the most effective in increasing HSPC production from hiPSCs.</p><p><strong>Conclusions: </strong>This study highlights the potential of the inotropic drug DH as a novel agent to enhance hematogenic differentiation and improve the yield of hiPSC-derived hematopoietic stem and progenitor cells (HSPCs). DH was found to significantly inhibit YAP activity, which in turn promoted hematopoietic specification, particularly when administered during the critical endothelial-to-hematopoietic transition (EHT) stage. These findings suggest that repurposing DH could offer a valuable strategy to increase the efficiency of hiPSC-derived HSPC production, advancing its potential for therapeutic and clinical applications in regenerative medicine and hematopoietic cell therapies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"298"},"PeriodicalIF":7.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258946","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":"Synergistic potential of bone marrow mesenchymal stem cells and miR181-a combinational therapy against multiple sclerosis.","authors":"Xin Xiu, Sijia Chen, Yumei Liu, Bo Sun, Hulun Li, Sifan Zhang, Xixi Yang, Yu Wei, Xichen Peng, Yan Wang, Yanping Wang, Junfeng Wu, Yao Zhang, Lili Mu, Qingfei Kong, Xijun Liu","doi":"10.1186/s13287-025-04401-7","DOIUrl":"10.1186/s13287-025-04401-7","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a progressive autoimmune disease characterized by massive inflammatory infiltration, demyelination, and subsequent axonal injury and neuronal damage in the central nervous system (CNS). The etiology of MS remains unclear and there is not yet a definitive therapeutic schedule for the disease. Bone marrow mesenchymal stem cells (BMSCs), exhibiting neuroimmune-modulatory functions to alleviate various autoimmune diseases, show great potential in the treatment of MS. However, the instability of BMSCs-mediated immunosuppression in vivo has limited their application. MiR181-a, a positive regulator of immune balance, which has a preference for T cells and B cells differentiation, but degrade rapidly upon entering systemic circulation due to their unstable molecular structure.</p><p><strong>Methods: </strong>We propose a synergistic therapy approach that combines the penetrative targeting capability of BMSCs with the immuno-modulatory effects of miR181-a by overexpressing miR181-a to BMSCs through lentivirus packaging system. With this strategy, on the basis of the establishment of the experimental autoimmune encephalomyelitis (EAE) model, miR181-a overexpressing BMSCs (miR181a-BMSCs) would have a stronger immuno-modulatory treatment benefit, in terms of attenuating MS development.</p><p><strong>Results: </strong>Indicate that this method prolongs the modulatory effects of BMSCs and resulted in significantly enhancements of the proliferation of regulatory B cells (Bregs), regulatory T cells (Tregs) and the inhibition of Th17 cells compared to the traditional BMSCs group. Moreover, 10-fold miRNA's concentration in the exosome of miR181a-BMSCs, leading to an increased duration of miRNAs to exert their biological effects. By immunotherapy and synergistic treatment, the effectiveness of the treatment is significantly enhanced, showing consistent results in different groups of the animal model.</p><p><strong>Conclusions: </strong>This strategy takes advantage of BMSCs and miRNA and thus presents an effective synergistic strategy for the treatment of autoimmune diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"300"},"PeriodicalIF":7.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258947","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":"Uncovering the bequeathing potential of apoptotic mesenchymal stem cells via small extracellular vesicles for its enhanced immunomodulatory and regenerative ability.","authors":"Meenakshi Mendiratta, Mohini Mendiratta, Yashvi Sharma, Ranjit Kumar Sahoo, Neena Malhotra, Sujata Mohanty","doi":"10.1186/s13287-025-04370-x","DOIUrl":"10.1186/s13287-025-04370-x","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal Stem Cells-derived Small Extracellular Vesicles endowed with regenerative cargo from their parent cells, have emerged as a promising avenue for cell-free therapeutics in regenerative medicine. Notably, deliberate induction of apoptosis in MSCs before sEV isolation has been identified as a strategy to augment the regenerative capabilities of MSCs-sEVs. This study explores a novel approach to enhance the immunomodulatory potential of MSC-sEVs through apoptosis induction and optimal tissue source to ensure consistent and improved clinical outcomes.</p><p><strong>Methods: </strong>Apoptosis was induced in tissue-specific MSCs using Staurosporine. sEVs^V and sEVs^Apo were isolated via ultracentrifugation. Invitro immune response was assessed via T-cell proliferation, T-regulatory cell induction & macrophage polarization assay. Mitochondrial bioenergetics was studied using MitoSOX staining and Seahorse assay in H2O2-treated HuH7 cells. These findings were validated invivo in the CCL4-induced Chronic Liver Disease model via Histopathological staining, biochemical parameters, and fibrotic, pro-inflammatory, and anti-inflammatory markers and assessed the mechanism by targeting TGF-β/SMAD pathway.</p><p><strong>Results: </strong>Our results demonstrate that sEVs^Apo exhibited significantly higher concentrations and superior immunomodulatory effects by suppressing CD3 + T-cell proliferation, promoting T-regulatory cell differentiation, and polarized macrophages towards M2-phenotype. In terms of tissue specificity, it was observed that WJ-sEVs were faring better. sEVs^Apo effectively reduced mitochondrial ROS & significantly improved oxidative phosphorylation. Invitro findings were corroborated in an invivo CLD model, wherein sEVs^Apo ameliorated fibrosis and inflammation, by inhibiting TGF-β/ SMAD2/3 pathway.</p><p><strong>Conclusion: </strong>This study concludes that apoptosis induction can be considered as minimum manipulation strategy to enhance the immunoregulatory and regenerative potential of MSCs-sEVs, thereby expanding their implication in immune disorder.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"290"},"PeriodicalIF":7.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249656","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":"Glioma stem cells: drivers of tumor progression and recurrence.","authors":"Jiaoyan He, Xiuwei Yan, Shaoshan Hu","doi":"10.1186/s13287-025-04352-z","DOIUrl":"10.1186/s13287-025-04352-z","url":null,"abstract":"<p><p>Glioma, a common malignancy of the central nervous system, attracts significant clinical attention due to its poor prognosis. Glioma stem cells (GSCs), characterized by stem-like properties and substantial heterogeneity, play a crucial role in tumor initiation, progression, and potential recurrence. Moreover, through complex interaction mechanisms, they contribute to the challenges associated with treatment. This review seeks to explore the distinctive characteristics and underlying mechanisms of GSCs, aiming to provide novel theoretical insights and practical strategies for precision therapy in glioma.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"293"},"PeriodicalIF":7.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249591","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":"KRT5^high TP63-expressing urothelial basal cells act as a driver to bladder urothelium regeneration in rabbit.","authors":"Jiasheng Chen, Mingming Yu, Lin Wang, Hua Xie, Yiqing Lv, Yichen Huang, Yue Hong, Fang Chen","doi":"10.1186/s13287-025-04417-z","DOIUrl":"10.1186/s13287-025-04417-z","url":null,"abstract":"<p><strong>Background: </strong>Urothelial regeneration is a crucial part of bladder tissue engineering. However, there is a lack of ideal \"seed cells\" in current practices. Here, we demonstrated that a sub-population of p63 positive basal cells could be activated and differentiate into intermediate and superficial umbrella cells after full-thickness mucosal resection in rabbit.</p><p><strong>Methods: </strong>A focal mucosal resection model was used to characterize the role of different urothelial cells during regeneration. Urothelial basal cells were isolated from rabbit bladder mucosa and cultured in vitro. The basal cells were then transplanted in vivo in a manner of cell sheet for reconstruction.</p><p><strong>Results: </strong>Via single-cell RNA sequencing (scRNA-seq), it has been confirmed that the cluster of KRT5^high TP63-expressing cells possesses a ''stemness'' signature which can give rise to lineage cell types sequentially. With a strong support from the underneath pre-set capsule vascular bed, the transplanted cell sheet could develop into a physio-morphology resembled to the native mucosa in vivo. Importantly, we validated that the bioengineered urothelium implemented perfect barrier function after implanted to bladder.</p><p><strong>Conclusions: </strong>In summary, bioengineering urothelium with KRT5^high TP63-expressing basal cells on a capsule vascular bed offers a promising strategy for bladder tissue engineering and provides a model for drug screening and bladder disease research.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"296"},"PeriodicalIF":7.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249595","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":"Hair growth stimulated by allogenic adipose-derived stem cells supplemented with ATP in a mouse model of dihydrotestosterone-induced androgenetic alopecia.","authors":"E López Bran, L Pozo Pérez, P Tornero Esteban, M L González Morales","doi":"10.1186/s13287-025-04372-9","DOIUrl":"10.1186/s13287-025-04372-9","url":null,"abstract":"<p><strong>Background: </strong>Androgenetic alopecia (AGA), also known as male or female pattern hair loss, is the most prevalent form of alopecia worldwide. Current treatments are based on hormone drugs, topical vasodilators and hair transplants. Newer options include stem cell therapy targeted at recovering the capacity for hair follicle regeneration. This study examines the effects of intradermally administering allogenic adipose-derived stem cells (ASCs) per se or supplemented with ATP in a mouse model of dihydrotestosterone (DHT)-induced AGA.</p><p><strong>Methods: </strong>Male and female C57BL6-strain mice were treated with DHT to induce AGA and then given injections of treatment solution in a defined area of the depilated back skin, and the same injections three days later. The treatments tested were several concentrations of ASCs combined with two ATP formulations. Photographs of the treated zones were taken on days 7, 10, 14, 17 and 21 and subjected to Image J analysis. On day 21, skin samples were also obtained for histological analysis. The main outcome measure was percentage treated surface area showing hair regrowth on treatment days 17 and 21 expressed as five categories: null, poor, moderate, intense and complete (20, 40, 60, 80 and 100% respectively).</p><p><strong>Results: </strong>The experimental groups found to show the highest number of male individuals with intense/complete hair regrowth on day 21 were those in which mice received low dose ASCs (1 ∙ 10⁶) combined either with liposomal ATP or non-liposomal ATP. Both these groups showed significant differences compared to controls. In females, while low dose ASC treatments and the high dose ASC + liposomal ATP treatment led to no hair regrowth improvement over the control treatment, medium dose ASC (2 × 10⁶) + non-liposomal ATP gave rise to greater regrowth scores.</p><p><strong>Conclusions: </strong>Hair regrowth was improved in all experimental groups in which male mice were administered stem cell solutions supplemented with ATP. In female mice, the highest hair regrowth scores were observed for the medium dose ASC + liposomal ATP treatment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"292"},"PeriodicalIF":7.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249592","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":"hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats.","authors":"Yu Tang, Yu He, Xingyu Huo, Juntong Chen, Maojiao Qian, Haoyu Huang, Yixuan Meng, Lianshuang Zhang, Feibo Xu, Yukun Zhang, Hongchu Bao, Yanlian Xiong","doi":"10.1186/s13287-025-04396-1","DOIUrl":"10.1186/s13287-025-04396-1","url":null,"abstract":"<p><strong>Background: </strong>One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunction brought on by POI. However, its therapeutic mechanism is still unclear and needs further exploration.</p><p><strong>Methods: </strong>POI model was established by intraperitoneal injection of cyclophosphamide (CTX) in female Wistar rats. These POI rats were treated with hUMSC-Exos for one week. In addition to in vivo experiments, in vitro POI models were also established. In vitro experiments, theca interstitial cells (TICs) treated with CTX were exposed to normal as well as let-7a-5p inhibitory hUMSC-Exos. The ovary structure, morphology, endocrine function, and reproductive ability of POI rats were observed by H&E staining and ELISA. Western blot, immunofluorescence staining (IF), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the autophagy-related indexes in ovary and TICs of POI rats in each group.</p><p><strong>Results: </strong>CTX induced abnormalities of ovarian morphology, structure, endocrine, and reproductive function in rats, and accompanied by autophagy of TICs. Notably, hUMSC-Exos diminishes ovarian structural and functional damage in POI rats and TICs autophagy via targeting the AMPK/mTOR pathway. Furthermore, downregulating let-7a-5p in hUMSC-Exos weakened their ability to prevent TICs autophagy.</p><p><strong>Conclusions: </strong>Overall, the findings suggested that hUMSC-Exos improves ovarian function in POI rats by inhibiting TICs autophagy via the let-7a-5p/AMPK/mTOR pathway. Our study provided further evidence that POI patients can benefit from hUMSC-Exos-mediated therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"291"},"PeriodicalIF":7.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249594","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}