Stem Cell Research & Therapy最新文献

{"title":"Human induced neural progenitor cells generated from three-dimensional aggregate-based culture significantly improve post-stroke recovery in tMCAO mice.","authors":"Zeqin Fu, Yue Hu, Yuxia Wang, Zhijie Liu, Mengyuan Li, Yanqiu Guo, Zhiwei Hu, Xingqiang Lai, Junyuan Hu, Yan Liao, Cheguo Cai","doi":"10.1186/s13287-025-04433-z","DOIUrl":"10.1186/s13287-025-04433-z","url":null,"abstract":"<p><strong>Background: </strong>Despite the high prevalence of cerebral ischemic stroke, effective clinical treatments remain limited. With the development of regenerative medicine, induced neural progenitor cells (iNPCs) demonstrate ideal potential and good availability for autologous transplantation therapy. However, current differentiation protocols for iNPCs still have room for improvement in terms of purity, reproducibility, scalability and differentiation potential.</p><p><strong>Methods: </strong>We aimed to develop a scalable, stable, and efficient 3D aggregate-based method for iNPC production in suspension culture, avoiding detrimental cell dissociation and replating processes. We evaluated the therapeutic potential of iNPCs in the chronic phase of a transient middle cerebral artery occlusion (tMCAO) mouse model and explored iNPC subpopulations via single-cell RNA sequencing to elucidate their pleiotropic therapeutic potentials.</p><p><strong>Results: </strong>iNPCs generated from three iPSC lines displayed high NPC marker expression and an average 176-fold cell expansion over the 12-day culture period. These iNPCs could spontaneously differentiate into both neurons and glial cells in vitro. In the tMCAO model, transplanted iNPCs remodeled the microenvironment by alleviating neuroinflammation, inhibiting chronic microgliosis and astrogliosis, promoting M2 polarization of microglia, and preserving astrocytic morphology in the ischemic penumbra. Mechanistically, iNPCs can be divided into four subpopulations, with neuroepithelia being the most abundant and capable of rapidly replenishing damaged cells and mitigating microenvironmental deterioration.</p><p><strong>Conclusions: </strong>We developed a simple and efficient 3D aggregate-based method for iNPC differentiation. These iNPCs showed excellent potential for post-stroke recovery and represent a valuable tool for clinical translation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"312"},"PeriodicalIF":7.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337091","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":"M2 macrophage-derived mitochondrial transplantation promotes periodontal bone regeneration by regulating metabolic homeostasis via activating p38-MAPK signaling pathway.","authors":"Yuzhuo Ma, Xiang Han, Ke Yan, Yiyang Yang, Kewei Zhang, Yue Wang, Xuerong Lv, Feiyang Wang, Xiaoqian Wang","doi":"10.1186/s13287-025-04444-w","DOIUrl":"10.1186/s13287-025-04444-w","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"315"},"PeriodicalIF":7.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337092","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 cell-derived exosomes-a promising therapeutic approach to improve neurocognitive disorders in chronic obstructive pulmonary disease.","authors":"Hui Xiao, Xiao Yu, Yushan Liu, Wenhua Jiang, Xiaoting Meng, Zhiyong Dong, Fang Wang","doi":"10.1186/s13287-025-04457-5","DOIUrl":"10.1186/s13287-025-04457-5","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and is often accompanied by neurocognitive disorders. It seriously affects the quality of life and treatment outcome of patients. COPD-induced neurocognitive disorders (COPD-NCDs) are driven by systemic inflammation, blood-brain barrier (BBB) disruption, and chronic hypoxia, but there is currently no effective treatment to prevent or reverse cognitive decline. Mesenchymal stem cell-derived exosomes (MSC-Exos) are nanoscale extracellular vesicles with unique bioactivity, which have shown great potential in the fields of nervous system diseases, respiratory diseases, bone and joint diseases. Different from traditional cell therapies, MSC-Exos have the advantages of non-immunogenicity, non-tumorigenicity, high stability and biocompatibility. In addition, MSC-Exos can also cross the BBB, regulate neuroinflammation, promote neurogenesis, enhance myelination and improve synaptic plasticity, thereby addressing the multifaceted pathogenesis of central nervous system (CNS) diseases. In this review, we first summarize the pathogenic mechanism of COPD-NCDs, and then summarize the multiple mechanisms of MSC-Exos improving NCDs based on the efficacy of MSC-Exos on other CNS diseases, emphasizing the theoretical basis and unique potential of MSC-Exos as a treatment for COPD-NCDs. Finally, we prospected the future research directions and potential problems of applying MSC-Exos to treat COPD-NCDs, future research should focus on optimizing the large-scale preparation of MSC-Exos, exploring their long-term safety, and advancing clinical translation to address the unmet needs of COPD-NCDs patients.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"314"},"PeriodicalIF":7.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337093","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 critical role of PDGFRa + Sca1 + fibroblasts in angiogenesis and vascular repair in the corpus cavernosum.","authors":"Biao Liu, Zitaiyu Li, Zhitao Han, Yuzhuo Chen, Yanghua Xu, Jiarong Xu, Hongji Hu, Ningjing Ou, Xiaoping Zheng, Yinghao Yin, Dongyi Peng, Liangyu Zhao, Yuxin Tang","doi":"10.1186/s13287-025-04434-y","DOIUrl":"10.1186/s13287-025-04434-y","url":null,"abstract":"<p><strong>Background: </strong>Erectile dysfunction (ED) is an important cause of reduced quality of life for men and their partners. A common pathological feature across various types of ED, including diabetes mellitus-induced ED (DMED) and bilateral cavernous nerve injury-induced ED (CNIED), is the loss of endothelial cells (ECs) and smooth muscle cells (SMCs) in the corpus cavernosum (CC). Stem cell-based therapies have garnered attention due to their potential to differentiate into specialized cell types, offering promise for the treatment of ED. Fibroblasts (FBs), the most abundant cell type in the CC, have raised considerable interest in recent years. However, the functional role of FBs in the progression of ED remains unclear.</p><p><strong>Methods: </strong>We established DMED and CNIED animal models and performed single-cell RNA sequencing (scRNA-seq) to analyze cell subsets within the pathological environments of these two ED types. To further investigate the cellular landscape, we combined spatial transcriptomics with scRNA-seq and multiplexed immunofluorescence to identify specific FB subsets in the CC.</p><p><strong>Results: </strong>scRNA-seq revealed a distinct subset of FBs that overexpress both Sca1 and PDGFRa. CytoTRACE analysis and Gene Set Enrichment Analysis (GSEA) indicated that PDGFRa + Sca1 + FBs may be associated with angiogenesis and possess the potential to differentiate into ECs and SMCs. Immunofluorescence analysis confirmed that PDGFRa + Sca1 + FBs were localized to the vessel walls, with co-localization of Sca1 and PDGFRa observed with markers for SMCs and ECs. Our findings shed light on the role of PDGFRa + Sca1 + FBs in the CC, demonstrating their involvement in angiogenesis and vascular repair. The depletion of these FBs in disease conditions may contribute to the exhaustion of ECs and SMCs, providing new insights into the pathogenesis of ED.</p><p><strong>Conclusion: </strong>These results open potential avenues for novel therapeutic strategies aimed at targeting PDGFRa + Sca1 + FBs to restore vascular function in ED.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"313"},"PeriodicalIF":7.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337094","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 influence of femtosecond laser intrastromal lenticules on the characteristics and maturity in tissue-engineered stem cell-derived retinal pigment epithelium sheets.","authors":"Gu Jianing, Su Zhanyu, Wang Yini, Chen Yuexi, Cui Zekai, Li Shengguo, Ding Chengcheng, Sheng Wang, Li Kangjun, Tang Shibo, Chen Jiansu","doi":"10.1186/s13287-025-04463-7","DOIUrl":"10.1186/s13287-025-04463-7","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in clinical trials have involved the transplantation of induced retinal pigment epithelium (iRPE) cells from stem cells in creating a functional monolayer that mimics the characteristics of natural adult RPE cells. One method of achieving this goal is through the use of tissue engineering. In this research, decellularised femtosecond laser intrastromal lenticules (dfLEN) were employed as a scaffold for cultivating a bioengineered iRPE monolayer sheet.</p><p><strong>Methods: </strong>iRPE cells were obtained by differentiating induced pluripotent stem cells (iPSC). These cells were then seeded on decellularized FLI-lenticules (dfLEN). The functionality, characterization, and oxidative stress of iRPE cultured on dfLEN were compared with those cultured on plates (TCP) using various assays such as immunofluorescence (IF), Edu, CCK8, ELISA, DFCH-DA, and JC-1. Additionally, RNA-seq assays and electron microscope (SEM and TEM) were used to test the iRPE characteristic on engineered dfLEN. Finally, we evaluated the biocompatibility of iRPE-dfLEN sheets by transplanting them into the subretinal space of New Zealand white rabbits.</p><p><strong>Results: </strong>The iRPE cells cultured on dfLEN exhibited morphology and physiology similar to that of native RPE tissue. The dfLEN not only increased the resistance capacity of iRPE cells but also improved their functional properties compared to TCP. In addition, our results indicate that dfLEN enhances the expression of genes associated with cilium assembly, resulting in notable improvements in ciliogenesis in iRPE cells. Finally, the dfLEN-iRPE sheets demonstrated favorable biocompatibility and some viability when transplanted into the subretinal space of rabbits for a period of 14 days.</p><p><strong>Conclusions: </strong>We determine that engineered RPE sheets using dfLEN scaffolds enhance RPE characteristics and functions, and suggest that dfLEN scaffolds promote cilium process maturation and polarization of iPSC-derived epithelial cells. Such a strategy for constructing iRPE sheets holds significant potential for advancing RPE cell therapy, disease models, and drug screening platforms.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"316"},"PeriodicalIF":7.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role and mechanism of mesenchymal stem cells in immunomodulation of type 1 diabetes mellitus and its complications: recent research progress and challenges: a review.","authors":"Chengran Wang, Yimeng Wu, Jinlan Jiang","doi":"10.1186/s13287-025-04431-1","DOIUrl":"10.1186/s13287-025-04431-1","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells are of great interest because of their multipotency, immune modulation capacity, and tissue and vascular regeneration effects. They are used in treating type 1 diabetes mellitus, helping improve the pancreatic environment and insulin secretion. Type 1 diabetes mellitus predominantly affects children and adolescents, with early onset and a prolonged course that can lead to multiorgan complications and related disorders. Studies using mesenchymal stem cells to treat type 1 diabetes mellitus have yielded promising results. This review discusses the common animal models of type 1 diabetes mellitus, mesenchymal stem cell immunotherapy mechanisms, and combined diabetes treatments. Its purpose is to summarize the current evidence on mesenchymal stem cell use in type 1 diabetes, providing insights for further research directions.</p><p><strong>Main findings: </strong>Current studies show that mesenchymal stem cells play an active role in the treatment of type 1 diabetes; however, clinical trials remain rare, necessitating more basic and preclinical research to identify optimal treatments.</p><p><strong>Conclusions: </strong>Mesenchymal stem cells can treat type 1 diabetes through a variety of immune mechanisms and also play a positive role in the treatment of type 1 diabetes complications. At the same time, it can be combined with other therapies to play a better therapeutic role.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"308"},"PeriodicalIF":7.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317868","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":"Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation.","authors":"Jie Chen, Yiwei Zhao, Chongmai Zeng, Guoli Tian, Zhicai Feng, Yang Cao","doi":"10.1186/s13287-025-04380-9","DOIUrl":"10.1186/s13287-025-04380-9","url":null,"abstract":"<p><strong>Background: </strong>Craniomaxillofacial sutures play a critical role in craniomaxillofacial development through continuous bone reconstruction and regeneration, processes modulated by mechanical tension. Bone suture stem cells (SuSCs) are central to these functions. Distraction osteogenesis, which promotes craniomaxillofacial suture growth, is a common therapeutic approach for craniofacial deformities. However, the underlying mechanisms by which mechanical forces drive suture and bone remodeling remain poorly understood, posing significant clinical challenges.</p><p><strong>Methods: </strong>To investigate these mechanisms, we established a rapid maxillary expansion (RME) model in mice to widen the midpalatal suture. Single-cell RNA sequencing (scRNA-seq) was employed to identify subsets of SuSCs responsive to mechanical tension and analyze their differentiation potential under varying conditions. Further functional studies were conducted to explore the role of DALR anticodon binding domain containing 3 (Dalrd3) and its associated tRNA 3-methylcytosine (m3C) modification in SuSCs under mechanical tension.</p><p><strong>Results: </strong>Our study identified a subset of SuSCs with multidirectional differentiation potential that shifted from a chondrogenic to an osteogenic trajectory in response to mechanical tension. Mechanical tension also upregulated Dalrd3 expression and its associated tRNA m3C modification in activated SuSCs. Knockdown of Dalrd3 in SuSCs significantly impaired osteogenic differentiation, proliferation, migratory capacity, and translational activity within the bone morphogenetic protein (BMP) signaling pathway. Furthermore, Dalrd3 knockdown suppressed the translational activity of inhibitor of DNA binding 3 (Id3), a key BMP-induced mediator of osteoblastogenesis. Restoring Id3 expression in Dalrd3-deficient SuSCs rescued their osteogenic, proliferative, and migratory functions.</p><p><strong>Conclusions: </strong>These findings reveal a translational regulatory mechanism in SuSCs activated by mechanical tension and underscore the pivotal role of Dalrd3 in suture remodeling and bone formation. The insights provided by this study have the potential to guide targeted therapeutic strategies for optimizing distraction osteogenesis and other treatments for craniofacial deformities.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"309"},"PeriodicalIF":7.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317867","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":"Mechanical harvesting of cell sheets: an efficient approach for bone and cartilage tissue engineering.","authors":"Fatemeh Leisi Mehrabani, Yalda Alibeigian, Mohamadreza Baghaban Eslaminejad, Samaneh Hosseini","doi":"10.1186/s13287-025-04411-5","DOIUrl":"10.1186/s13287-025-04411-5","url":null,"abstract":"<p><p>Cell sheet engineering (CSE) has demonstrated significant promise for the advancement and application of tissue-engineered constructs in the fields of tissue engineering and regenerative medicine. In this technology, cells are cultured to form a monolayer, which is then detached from the culture surface as a complete sheet. This process preserves cell interactions, maintains cellular phenotypes and functions, and retains the integrity of the cell-extracellular matrix (ECM). A main characteristic of the cell sheet is its ability to retain the native ECM components secreted by cells. When the ECM is preserved in cell sheets, cells are surrounded by a much more biologically appropriate environment to increase their regenerative potential, thereby offering more native conditions for cell growth and differentiation. CSE has shown promising results in a wide range of applications, including bone and cartilage. The cell sheets can be directly transplanted to the target site, where they integrate with the host tissue and enhance regeneration. The main challenge in CSE is how to detach an intact cell sheet without disturbing the ECM and cell‒cell connections. There are various methods for removing cell sheets that lead to the harvesting of intact cell sheets. Among the various methods for harvesting cell sheets, temperature-responsive systems and mechanical peeling are the most common. Mechanical harvesting, in particular, is a simple, cost-effective, accessible method that is widely used in research, especially in the scope of bone and cartilage tissue engineering. This article aims to review the application of cell sheets in bone and cartilage tissue engineering, with a focus on practical and cost-effective mechanical harvesting methods.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"310"},"PeriodicalIF":7.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317866","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":"CHD7 regulates definitive endodermal and mesodermal development from human embryonic stem cells.","authors":"Rong Hu, Jin Zhao, Kuan Chen Lai, Shikun Wang, Jianqing Zheng, Christopher Stoddard, Laijun Lai","doi":"10.1186/s13287-025-04437-9","DOIUrl":"10.1186/s13287-025-04437-9","url":null,"abstract":"<p><strong>Background: </strong>CHD7 encodes an ATP-dependent chromodomain helicase DNA binding protein; mutations in this gene lead to multiple developmental disorders, including CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retardation of growth and development, Genital hypoplasia, and Ear anomalies) syndrome. How the mutations cause multiple defects remains largely unclear. Embryonic definitive endoderm (DE) generates the epithelial compartment of vital organs such as the thymus, liver, pancreas, and intestine.</p><p><strong>Methods: </strong>In this study, we used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technique to delete the CHD7 gene in human embryonic stem cells (hESCs) to generate CHD7 homozygous mutant (CHD7^-/-), heterozygous mutant (CHD7^+/-), and control wild-type (CHD7^+/+) cells. We then investigated the ability of the hESCs to develop into DE and the other two germ layers, mesoderm and ectoderm in vitro. We also compared global gene expression and chromatin accessibility among the hESC-DE cells by RNA sequencing (RNA-seq) and the assay for transposase-accessible chromatin with sequencing (ATAC-seq).</p><p><strong>Results: </strong>We found that deletion of CHD7 led to reduced capacity to develop into DE and mesoderm in a dose-dependent manner. Loss of CHD7 led to significant changes in the expression and chromatin accessibility of genes associated with several pathways. We identified 40 genes that were highly down-regulated in both the expression and chromatin accessibility in CHD7 deleted hESC-DE cells.</p><p><strong>Conclusions: </strong>CHD7 is critical for DE and mesodermal development from hESCs. Our results provide new insights into the mechanisms by which CHD7 mutations cause multiple congenital anomalies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"311"},"PeriodicalIF":7.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317865","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":"Adipose-derived stem cells extracellular vesicles enhance diabetic wound healing via CCN2/PI3K/AKT pathway: therapeutic potential and mechanistic insights.","authors":"Yu-Lu Zhou, Shingo Ogura, Hao Ma, Rong-Bin Liang, Shao-Yihan Fang, Yue-Ming Wang, Yan Wo, Wen-Jin Wang, De-Wu Liu","doi":"10.1186/s13287-025-04354-x","DOIUrl":"10.1186/s13287-025-04354-x","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cells extracellular vesicles (ADSCs-EVs) hold significant promise in tissue repair and regeneration. While they have been reported to enhance diabetic wound healing, the precise mechanisms remain unclear.</p><p><strong>Methods: </strong>ADSCs-EVs were isolated via ultracentrifugation and characterized through transmission electron microscopy, Western blot, and nanoparticle tracking analysis. Their effects on human umbilical vein endothelial cells (HUVECs) and RAW 264.7 macrophages were assessed in vitro, focusing on cell proliferation, migration, tube formation, and macrophage polarization. A diabetic rat wound model was used to evaluate their therapeutic impact on wound healing and angiogenesis, with histological and immunofluorescence analyses. mRNA sequencing identified Cellular communication network factor 2(CCN2) as a key upregulated gene, leading to further exploration of its role in ADSCs-EVs-mediated angiogenesis and wound healing via the PI3K/AKT pathway. Gene silencing (si-CCN2) and pharmacological inhibition (LY294002) were employed both in vitro and in vivo.</p><p><strong>Results: </strong>ADSCs-EVs were successfully isolated and characterized. In vitro, ADSCs-EVs promoted HUVEC proliferation, migration, and tube formation, and facilitated macrophage polarization to the M2 phenotype. In vivo studies using a diabetic rat wound model confirmed the pro-healing effects of ADSCs-EVs, including enhanced angiogenesis, granulation tissue formation, and accelerated wound closure. mRNA sequencing revealed that CCN2 expression was significantly upregulated in diabetic wound tissues treated with ADSCs-EVs. Further experiments showed that inhibiting CCN2 expression (si-CCN2) or blocking the PI3K/AKT pathway (LY294002) partially suppressed HUVEC proliferation, migration, tube formation, and angiogenesis, and counteracted the pro-healing effects of ADSCs-EVs.</p><p><strong>Conclusions: </strong>ADSCs-EVs promote diabetic wound healing through the CCN2/PI3K/AKT pathway, offering a promising therapeutic target for diabetic wound repair.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"304"},"PeriodicalIF":7.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302774","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}