Stem Cell Research & Therapy最新文献

{"title":"Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases.","authors":"Haiming Li, Peng Zhang, Minghui Lin, Kang Li, Cunxin Zhang, Xiao He, Kai Gao","doi":"10.1186/s13287-025-04167-y","DOIUrl":"10.1186/s13287-025-04167-y","url":null,"abstract":"<p><p>Bone-related diseases impact a large portion of the global population and, due to their high disability rates and limited treatment options, pose significant medical and economic challenges. Mesenchymal stem cells (MSCs) can differentiate into multiple cell types and offer strong regenerative potential, making them promising for treating various diseases. However, issues with the immune response and cell survival limit the effectiveness of cell transplantation. This has led to increased interest in cell-free stem cell therapy, particularly the use of exosomes, which is the most studied form of this approach. Exosomes are extracellular vesicles that contain proteins, lipids, and nucleic acids and play a key role in cell communication and material exchange. Pyroptosis, a form of cell death involved in innate immunity, is also associated with many diseases. Studies have shown that MSC-derived exosomes have therapeutic potential for treating a range of conditions by regulating inflammation and pyroptosis. This study explored the role of MSC-derived exosomes in modulating pyroptosis to improve the treatment of bone-related diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"68"},"PeriodicalIF":7.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411066","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":"Therapeutic potential of exosomal lncRNAs derived from stem cells in wound healing: focusing on mesenchymal stem cells.","authors":"Ali Morabbi, Mohammad Karimian","doi":"10.1186/s13287-025-04200-0","DOIUrl":"10.1186/s13287-025-04200-0","url":null,"abstract":"<p><p>The self-renewal ability and multipotency of stem cells give them great potential for use in wound healing. Stem cell-derived exosomes, owing to their close biological resemblance to their parent cells, offer a more efficient, safer, and economical approach for facilitating cellular communication and interactions within different environments. This potential makes them particularly valuable in the treatment of both acute and chronic wounds, such as lacerations, burns, and diabetic ulcers. Long non-coding RNAs (lncRNAs) enclosed in exosomes, as one of the leading actors of these extracellular microvesicles, through interaction with miRNAs and regulation of various signaling pathways involved in inflammation, angiogenesis, cell proliferation, and migration, could heal the wounds. Exosome-derived lncRNAs from stem cells facilitate extracellular matrix remodeling through interaction between macrophages and fibroblasts. Moreover, alongside regulating the expression of inflammatory cytokines, controlling reactive oxygen species levels, and enhancing autophagic activity, they also modulate immune responses to support wound healing. Regulating the expression of genes and signaling pathways related to angiogenesis, by increasing blood supply and accelerating the delivery of essential substances to the wound environment, is another effect exosomal lncRNAs derived from stem cells for wound healing. These lncRNAs can also enhance skin wound healing by regulating homeostasis, increasing the proliferation and differentiation of cells involved in the wound-healing process, and enhancing fibroblast viability and migration to the injury site. Ultimately, exosome-derived lncRNAs from stem cells offer valuable and novel insights into the molecular mechanisms underlying improved wound healing. They can pave the way for potential therapeutic strategies, fostering further research for a better future. Meanwhile, exosomes derived from mesenchymal stem cells, due to their exceptional regenerative properties, as well as the lncRNAs derived from these exosomes, have emerged as one of the innovative tools in wound healing. This review article aims to narrate the cellular and molecular roles of exosome-derived lncRNAs from stem cells in enhancing wound healing with a focus on mesenchymal stem cells.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"62"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399977","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":"Development and evaluation of siRNA-mediated gene silencing strategies for ADO2 therapy utilizing iPSCs model and DMPC-SPIONs delivery system.","authors":"Jiajun Xu, Gengshuo Chen, Chune Mo, Yu Sha, Sha Luo, Minglin Ou","doi":"10.1186/s13287-025-04151-6","DOIUrl":"10.1186/s13287-025-04151-6","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant osteodystrophy type II (ADO2) is an inherited disease characterized by an abnormal increase in bone mineral density, and CLCN7 (R286W) is its most common causative mutation. The aim of this study was to explore the new idea of siRNA technology applied to the in vitro treatment of ADO2.</p><p><strong>Methods: </strong>Urinary-derived cells from ADO2 patients were collected to establish induced pluripotent stem cells (iPSCs) model. The siRNA targeting CLCN7 (R286W) mutant mRNA was designed. the cytotoxicity of the delivery vector DMPC-SPIONs was comprehensively evaluated by CCK-8 assay, flow cytometry and scratch assay. Finally, qPCR was utilized to verify the post-transcriptional silencing effect of siRNAs.</p><p><strong>Results: </strong>We found that DMPC-SPIONs had low cytotoxicity and were able to effectively deliver siRNAs into ADO2-iPSCs. qPCR confirmed that siRNA-DMPC-SPIONs were able to significantly reduce the expression level of mutant CLCN7 (66%), while there was no significant effect on the expression of wild-type CLCN7.</p><p><strong>Conclusions: </strong>This study developed a gene silencing strategy based on siRNAs and DMPC-SPIONs, which provides a potential new approach for the treatment of ADO2 and demonstrates the potential application of siRNA technology in the treatment of autosomal dominant genetic diseases.</p><p><strong>Innovative statements: </strong>In this study, we used the established ADO2-iPSCs using patient's urine-derived cells to explore the safety and efficacy of siRNA technology based on the principle of RNA interference for ADO2 treatment for the first time. In addition, we chose DMPC-SPIONs as the delivery vehicle for siRNA, which cleverly exploits the advantages of nanoparticles such as superparamagnetism, low cytotoxicity, and good bio-histocompatibility.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"66"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400045","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":"Human hair follicle-derived mesenchymal stem cells improve ovarian function in cyclophosphamide-induced POF mice.","authors":"Jinhua Mo, Hong Hu, Pengdong Li, Yang Ye, Wanle Chen, Lei Chen, Jing Qiao, Xiaoying Zhao, Qiuxia Yan, Cairong Chen","doi":"10.1186/s13287-024-04097-1","DOIUrl":"10.1186/s13287-024-04097-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Mesenchymal stem cell (MSCs) of different tissue origins have become a new option for the treatment of premature ovarian failure (POF) as they can recovery the ovarian function. However, there were rarely researches about human hair follicle-derived mesenchymal stem cells (HF-MSCs) in POF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;In this study, we compared the effects of HF-MSCs and human umbilical cord mesenchymal stem cells (HU-MSCs) on POF models to explore the underlying molecular mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Female mice received intraperitoneal cyclophosphamid for 10 days to induce the POF mice model. One week after drug withdrawal, the mice were randomly divided into four groups according to the tail vein injection of drugs, which were: Control group (CON), Premature ovarian failure group (POF), HF-MSCs treatment group (P-H group) and HU-MSCs treatment group (P-U group). Which Treatment once a week for 4 consecutive times. Serum and ovarian tissues were collected 2 weeks after the last treatment, and fertility was performed by mating. ELISA, HE staining, transmission electron microscopy (TEM) were applied to evaluate the ovarian function, oocytes quantity and quality, and the mechanism was verified by qRT-PCR and western blot. In addition, the tumorigenic risk of organs was assessed by long-term observation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The POF mice model was successfully established by intraperitoneal injection of cyclophosphamide 100 mg/kg/d for 10 days. Compared with POF group, two weeks after transplantation, serum FSH decreased, AMH and E2 increased in the P-H and P-U groups of mice (p &lt; 0.05), but there was no significant difference between the P-H and P-U groups (p &gt; 0.05). In addition, the number of primary follicles, secondary follicles and antral follicles in both P-H and P-U groups were significantly increased (p &lt; 0.05), while the atretic follicles was significantly decreased (p &lt; 0.05). The pups in POF group was significantly lower than that in P-H group and P-U group (p &lt; 0. 01). Furthermore, those effects was more significant in P-H group than in P-U group (p &lt; 0.05). In addition, the mitochondrial ultramicrostructure of the ovaries in the four groups showed a significant difference in the mitochondrial morphologies and number. In the POF group, the mitochondria presented a spheroids structure with fewer numbers, serious vacuolation and a disordered mitochondrial cristae arrangement. Nevertheless, after MSCs transplantation into the P-H and P-U group, we could observe ameliorative mitochondrial cristae alignment and vacuolation, as well as a small number of long rod-like structures. Mechanism study showed that KEAP1 protein expression was decreased in the P-H group, which increased the nuclear translocation of NRF2 and upregulated the expression of downstream HO-1 protein. At last, the possibility of tumor development after transplantation of HF-MSCs was excluded by long-term obse","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"67"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400054","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":"Efficacy and safety of mesenchymal stromal cell transplantation in the treatment of autoimmune and rheumatic immune diseases: a systematic review and meta-analysis of randomized controlled trials.","authors":"Liuting Zeng, Chang Liu, Yang Wu, Shuman Liu, Yaru Zheng, Wensa Hao, Dandan Wang, Lingyun Sun","doi":"10.1186/s13287-025-04184-x","DOIUrl":"10.1186/s13287-025-04184-x","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune and rheumatic immune diseases through randomized controlled trials (RCTs).</p><p><strong>Methods: </strong>Two researchers conducted a comprehensive search of Chinese and English databases from their inception until Dec. 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software.</p><p><strong>Results: </strong>A total of 42 relevant RCTs, involving 2,183 participants, were ultimately included in this study. These RCTs encompassed four types of rheumatic immune and bone diseases, namely rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis, systemic sclerosis arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease, multiple sclerosis, primary Sjögren's syndrome (PSS). The systematic review indicates that MSC transplantation may improve spondyloarthritis, RA, PSS. The meta-analysis reveals that MSC transplantation significantly improved symptoms in patients with OA [VAS (visual analogue scale): bone marrow: SMD = - 0.95, 95% CI - 1.55 to - 0.36, P = 0.002; umbilical cord: SMD = - 1.25, 95% CI - 2.04 to - 0.46, P = 0.002; adipose tissue: SMD = -1.26, 95% CI -1.99 to - 0.52, P = 0.0009)], SLE [Systemic lupus erythematosus disease activity index (SLEDAI): SMD = - 2.32, 95% CI - 3.59 to - 1.06, P = 0.0003], inflammatory bowel disease [clinical efficacy: RR = 2.02, 95% CI 1.53 to 2.67, P < 0.00001]. However, MSC transplantation may not improve the symptoms of multiple sclerosis and systemic sclerosis (Ssc). Importantly, MSC transplantation did not increase the incidence of adverse events (OA: RR = 1.23, 95% CI 0.93 to 1.65, P = 0.15; SLE: RR = 0.83, 95% CI 0.28 to 2.51, P = 0.76; Inflammatory bowel disease: RR = 0.99, 95% CI 0.81 to 1.22, P = 0.96; Multiple sclerosis: RR = 1.12, 95% CI 0.81 to 1.53, P = 0.50), supporting its safety profile across the included studies. These findings suggest that MSC transplantation holds promise for several rheumatic and autoimmune diseases while highlighting areas where further research is warranted.</p><p><strong>Conclusion: </strong>MSC transplantation may have the potential to treat autoimmune and rheumatic immune diseases. Moreover. MSC transplantation appears to be relatively safe and could be considered as a viable alternative treatment option for autoimmune and rheumatic immune diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"65"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400049","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":"Identifying differentiation markers between dermal fibroblasts and adipose-derived mesenchymal stromal cells (AD-MSCs) in human visceral and subcutaneous tissues using single-cell transcriptomics.","authors":"Magdalena Koczkowska, Anna Kostecka, Małgorzata Zawrzykraj, Kamil Myszczyński, Aneta Skoniecka, Milena Deptuła, Agata Tymińska, Katarzyna Czerwiec, Marcin Jąkalski, Jacek Zieliński, David K Crossman, Michael R Crowley, Mirosława Cichorek, Piotr M Skowron, Michał Pikuła, Arkadiusz Piotrowski","doi":"10.1186/s13287-025-04185-w","DOIUrl":"10.1186/s13287-025-04185-w","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived mesenchymal stromal cells (AD-MSCs) and fibroblasts are both widely used in regenerative medicine, demonstrating significant potential for personalized cell therapy. A major challenge in their use lies in their high biological similarity, encompassing morphology, differentiation capabilities, and flow cytometric markers, making their distinction difficult.</p><p><strong>Methods: </strong>In our study, we aimed to compare AD-MSCs obtained from two types of adipose tissue, subcutaneous and visceral, alongside skin fibroblasts. Notably, all tissue samples were sourced from the same donors. We analyzed the cells for surface antigens via flow cytometry and conducted single-cell RNA sequencing, followed by verification with quantitative PCR (qPCR).</p><p><strong>Results: </strong>Our results revealed phenotypic similarities between the isolated AD-MSCs and dermal fibroblasts, particularly in the expression of markers characteristic of AD-MSCs. However, through in-depth analyses, we identified distinct differences between these cell types. Specifically, we pinpointed 30 genes exhibiting the most significant variations in expression between AD-MSCs and fibroblasts. These genes are associated with biological processes such as tissue remodeling, cell movement, and activation in response to external stimuli. Among them, MMP1, MMP3, S100A4, CXCL1, PI16, IGFBP5, COMP were further validated using qPCR, clearly demonstrating their potential to differentiate between AD-MSCs and fibroblasts.</p><p><strong>Conclusions: </strong>Our scRNA-seq analysis elucidates the transcriptional landscape of AD-MSCs and fibroblasts with unprecedented resolution, highlighting both the population-specific markers and the intrapopulation heterogeneity. Our findings underscore the importance of employing high-resolution techniques for cell identification.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"64"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400069","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":"Induction of the p21/CDK6 pathway and alteration of the immune microenvironment by the stem cell marker CBX3 in melanoma.","authors":"Wanxian Chen, Linsa Zhou, Jingjing Jiang, Jiasheng Chen, Deyi Geng, Yaokun Chen, Xiaosha Han, Qihu Xie, Genghong Guo, Xuefen Chen, Shijie Tang, Xiaoping Zhong","doi":"10.1186/s13287-025-04179-8","DOIUrl":"10.1186/s13287-025-04179-8","url":null,"abstract":"<p><strong>Background: </strong>As one of the stem cell markers, chromobox protein homolog 3 (CBX3) participates in multiple signaling pathways that affect the progression of various tumors. However, the role of CBX3 in melanoma remains unclear, and the mechanisms by which CBX3 may regulate immunotherapy outcome remain largely unknown.</p><p><strong>Methods: </strong>We used the Cancer Genome Atlas, Genotype-Tissue Expression portal, and Gene Expression Omnibus database to estimate CBX3 expression and its prognostic effect in melanoma. The role of CBX3 in proliferation and migration of melanoma cells were examined using the CCK8, cloning, wound healing, and transwell assays. The effect of CBX3 on melanoma tumorigenesis was assessed using an in vivo animal model. The role of CBX3 in cell cycle was examined using flow cytometry, and expression levels of cell cycle-related genes and proteins in cells with altered CBX3 levels were analyzed using qPCR and western blotting. The function of CBX3 in the immune microenvironment of melanoma was studied using single-cell RNA sequencing and public databases.</p><p><strong>Results: </strong>We found that CBX3 was highly expressed in melanoma with poor prognosis. CBX3 promoted the proliferation and migration of melanoma cells in vivo and in vitro. Functional analysis revealed that CBX3 regulates cell cycle, as it accelerated the G1 to S transition, decreased p21 expression, and increased CDK6 expression. Finally, single-cell sequencing and immune-related assays showed that CBX3 is immunogenic and can change the immune microenvironment of melanoma.</p><p><strong>Conclusions: </strong>We conclude that the stem cell marker, CBX3 activates the p21/CDK6 pathway and alters the immune microenvironment in melanoma.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"63"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400001","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 remission after fetal liver transplantation in acute leukemia: a 30-year follow-up report of two cases.","authors":"Jing-Wen Niu, Jiangwei Hu, Hu Chen, Bin Zhang, Liangding Hu","doi":"10.1186/s13287-024-04119-y","DOIUrl":"10.1186/s13287-024-04119-y","url":null,"abstract":"<p><p>Fetal liver hematopoietic stem cells (HSCs) have the capacity to temporarily engraft, thereby facilitating the reconstitution of hematopoiesis without severe graft-versus-host disease (GVHD). In two cases of acute leukemia, the patients underwent fetal liver transplantation (FLT), receiving cells from multiple donors at doses ranging from 7.02 to 8.3 × 10^8 cells/kg, following an intensive conditioning regimen in 1983 and 1985. Remarkably, both individuals have since achieved sustained complete remission and hematopoietic recovery, and have maintained a normal life for over three decades. Although FLT is no longer a viable clinical option, the positive outcomes of these cases are noteworthy and are shared herein. Our findings underscore the potential of FLT to offer short-term hematopoietic support, contributing to the recovery of patients with acute leukemia and may inspire research into ideal HSCs that emulate the characteristics of fetal liver cells for future transplantation applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"61"},"PeriodicalIF":7.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383259","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":"Hematopoietic stem cells: Understanding the mechanisms to unleash the therapeutic potential of hematopoietic stem cell transplantation.","authors":"Amjad Ahmed Aljagthmi, Amal Kamal Abdel-Aziz","doi":"10.1186/s13287-024-04126-z","DOIUrl":"10.1186/s13287-024-04126-z","url":null,"abstract":"<p><p>Hematopoietic stem cell transplantation (HSCT) is a promising approach in regenerative medicine and serves as a standard treatment for different malignant and non-malignant conditions. Despite its widespread applications, HSCT is associated with various complications that compromise patients' lives and pose considerable risks of morbidity and mortality. Understanding the molecular physiology of HSCs is fundamental to ultimately enhance the mobilization, engraftment and differentiation of HSCs, thus unleashing the full therapeutic potential of HSCT in the treated patients. This review outlines the current understanding of HSC biology and its relevance to the clinical challenges associated with HSCT. Furthermore, we critically discuss the pros and cons of the preclinical murine models exploited in the HSCT field. Understanding the molecular physiology of HSCs will ultimately unleash the full therapeutic potential of HSCT. HSCs derived from induced pluripotent stem cells (iPSCs) might present an attractive tool which could be exploited preclinically and clinically. Nonetheless, further studies are warranted to systematically evaluate their potential in terms of improving the therapeutic outcome and minimizing the adverse effects of HSCT.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"60"},"PeriodicalIF":7.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383256","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 from perinatal tissues promote diabetic wound healing via PI3K/AKT activation.","authors":"Jiawei Huang, Qingwen Deng, Lai Ling Tsang, Guozhu Chang, Jinghui Guo, Ye Chun Ruan, Chi Chiu Wang, Gang Li, Hon Fai Chan, Xiaohu Zhang, Xiaohua Jiang","doi":"10.1186/s13287-025-04141-8","DOIUrl":"10.1186/s13287-025-04141-8","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs) represent a major complication of diabetes, often leading to poor healing outcomes with conventional treatments. Mesenchymal stem cell (MSC) therapies have emerged as a promising alternative, given their potential to modulate various pathways involved in wound healing. This study evaluates and compares the therapeutic potential of MSCs derived from perinatal tissues-human umbilical cord MSCs (hUCMSCs), human chorionic villi MSCs (hCVMSCs), and human decidua basalis MSCs (hDCMSCs)-in a diabetic wound healing model.</p><p><strong>Methods: </strong>We performed in vitro and in vivo studies to compare the efficacy of hUCMSCs, hCVMSCs, and hDCMSCs. Mass spectrometry was used to analyze the secreted proteins of the MSCs. We incorporated the MSCs into a polyethylene glycol diacrylate (PEGDA) and sodium alginate (SA) hydrogel matrix with collagen I (Col-I) to evaluate their effects on wound healing.</p><p><strong>Results: </strong>All three types of MSCs promoted wound healing, with hUCMSCs and hCVMSCs showing stronger effects compared to hDCMSCs. Both hUCMSCs and hCVMSCs demonstrated robust wound healing kinetics, with enhanced keratinocyte proliferation (KRT14⁺/Ki67⁺ cells), maturation (KRT10/KRT14 ratio), and angiogenesis. In vitro studies demonstrated that the MSC-derived secretome enhanced keratinocyte proliferation and migration, endothelial cell function and stem cell recruitment, indicating robust paracrine effects. Mass spectrometry revealed a conserved set of proteins including THBS1 (thrombospondin 1), SERPINE1 (serpin family E member 1), ANXA1 (annexin A1), LOX (lysyl oxidase), and ITGB1 (integrin beta-1) which are involved in extracellular matrix (ECM) organization and wound healing, with the PI3K/AKT signaling pathway playing a central role. The PEGDA/SA/Col-I hydrogel demonstrated a unique balance of mechanical and biological properties and an optimal environment for MSC viability and function. Application of either hUCMSC- or hCVMSC-laden hydrogels resulted in accelerated wound closure, improved re-epithelialization, increased collagen deposition, and enhanced vascularization in vivo.</p><p><strong>Conclusions: </strong>MSCs From perinatal tissues particularly hUCMSCs and hCVMSCs significantly enhance diabetic wound healing through PI3K/AKT pathway activation while hDCMSCs exhibited weaker efficacy. The PEGDA/SA/Col-I hydrogel supports MSC viability and function offering a promising scaffold for DFU treatment. These findings underscore the potential of specific perinatal MSCs and optimized hydrogel formulations in advancing diabetic wound care.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"59"},"PeriodicalIF":7.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374840","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}