Stem Cell Research & Therapy最新文献

{"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}

{"title":"Bridging the gap: clinical translation of adipose-derived stem cells - a scoping review of clinical trials.","authors":"Hankun Su, Hoksan Chau, Qilin Li, Fen Xiao, Yuanyuan Sun, Jingjing Chen, Yayi He, Jinyao Ning, Qin Hu, Yujie Xiao, Caiwen Li, Bixia Huang, Jing Zhao, Yanping Li, Hui Li","doi":"10.1186/s13287-025-04405-3","DOIUrl":"10.1186/s13287-025-04405-3","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cells (ADSCs) have emerged as a promising therapeutic tool in regenerative medicine due to their multipotency, immunomodulatory properties, and ease of procurement. Despite extensive preclinical research, the clinical translation of ADSCs remains fragmented, with challenges in standardization, reproducibility, and evidence synthesis.</p><p><strong>Objective: </strong>This scoping review, complemented by bibliometric analysis, aims to map the landscape of randomized controlled trials (RCTs) evaluating ADSC therapies, identify gaps between basic research and clinical translation, and highlight emerging trends in the field.</p><p><strong>Methods: </strong>A systematic search of Web of Science, PubMed, Embase, ClinicalTrials.gov, EudraCT, and ChiCTR database (2009-2025) identified 82 RCTs. Bibliometric analysis of preclinical studies was conducted using VoSviewer to visualize keyword clusters and temporal trends. Data on trial characteristics, endpoints, and translational challenges were extracted and synthesized.</p><p><strong>Results: </strong>The 82 included RCTs spanned 17 medical specialties, with orthopedics (26.8%), dermatology (14.6%), and neurology (9.7%) being the most studied. Spain (21.95%) and China (18.29%) and the USA (15.85%) led trial numbers, but 97% were single-country studies with a median sample size of 40. Primary endpoints trends from safety to efficacy. Bibliometric analysis revealed three clusters: stem cell sources and basic biology, orthopedic applications, and tissue regeneration mechanisms. Key gaps included protocol heterogeneity (e.g., isolation methods, cryopreservation variability), regulatory fragmentation, limited long-term follow-up, and inconsistent clinical outcomes, particularly in neurology. Emerging trends highlighted the therapeutic potential of stromal vascular fraction (SVF) and ADSC-derived exosomes.</p><p><strong>Conclusions: </strong>While ADSCs demonstrate significant therapeutic potential, clinical translation is hindered by standardization deficits and mechanistic knowledge gaps. Future research should prioritize international collaboration, large-scale trials, and mechanistic studies to optimize ADSC therapies. Innovations in SVF and exosome-based treatments represent promising avenues for advancing regenerative medicine.</p><p><strong>Trial registry: </strong>This scoping review was preregistered at OSF platform: https://doi.org/10.17605/OSF.IO/YKHW3 .</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"288"},"PeriodicalIF":7.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249590","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":"High-throughput robotic isolation of human iPS cell clones reveals frequent homozygous induction of identical genetic manipulations by CRISPR-Cas9.","authors":"Gou Takahashi, Minato Maeda, Kayoko Shinozaki, Gakuro Harada, Saburo Ito, Yuichiro Miyaoka","doi":"10.1186/s13287-025-04414-2","DOIUrl":"10.1186/s13287-025-04414-2","url":null,"abstract":"<p><strong>Background: </strong>Genome editing in human iPS cells is a powerful approach in regenerative medicine. CRISPR-Cas9 is the most common genome editing tool, but it often induces byproduct insertions and deletions in addition to the desired edits. Therefore, genome editing of iPS cells produces diverse genotypes. Existing assays mostly analyze genome editing results in cell populations, but not in single cells. However, systematic profiling of genome editing outcomes in single iPS cells was lacking. Due to the high mortality of human iPS cells as isolated single cells, it has been difficult to analyze genome-edited iPS cell clones in a high-throughput manner.</p><p><strong>Methods: </strong>In this study, we developed a method for high-throughput iPS cell clone isolation based on the precise robotic picking of cell clumps derived from single cells grown in extracellular matrices. We first introduced point mutations into human iPS cell pools by CRISPR-Cas9. These genome-edited human iPS cells were dissociated and cultured as single cells in extracellular matrices to form cell clumps, which were then isolated using a cell-handling robot to establish genome-edited human iPS cell clones. Genome editing outcomes in these clones were analyzed by amplicon sequencing to determine the genotypes of individual iPS cell clones. We identified and distinguished the sequences of different insertions and deletions induced by CRISPR-Cas9 while determining their genotypes. We also cryopreserved the established iPS cell clones and recovered them after determining their genotypes.</p><p><strong>Results: </strong>We analyzed over 1,000 genome-edited iPS cell clones and found that homozygous editing was much more frequent than heterozygous editing. We also observed frequent homozygous induction of identical genetic manipulations, including insertions and deletions, such as 1-bp insertions and 8-bp deletions. Moreover, we successfully cryopreserved and then recovered genome-edited iPS cell clones, demonstrating that our cell-handling robot-based method is valuable in establishing genome-edited iPS cell clones.</p><p><strong>Conclusions: </strong>This study revealed a previously unknown property of genome editing in human iPS cells that identical sequence manipulations tend to be induced in both copies of the target sequence in individual cells. Our new cloning method and findings will facilitate the application of genome editing to human iPS cells.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"295"},"PeriodicalIF":7.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249593","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}