Stem Cell Research & Therapy最新文献

筛选
英文 中文
Therapeutic evaluation of iPSC-derived CD146+ mesenchymal stem cells in ulcerative colitis: biological properties and potential mechanisms. ipsc衍生的CD146+间充质干细胞治疗溃疡性结肠炎的疗效评估:生物学特性和潜在机制
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-14 DOI: 10.1186/s13287-025-04695-7
Lv Tian, Yiming Wang, Lei Shen, Mingru Zong, Jun Fan, Yuxin Lu, Xiaochen Cheng, Li Du, Lin Zhang, Fengjun Xiao
{"title":"Therapeutic evaluation of iPSC-derived CD146+ mesenchymal stem cells in ulcerative colitis: biological properties and potential mechanisms.","authors":"Lv Tian, Yiming Wang, Lei Shen, Mingru Zong, Jun Fan, Yuxin Lu, Xiaochen Cheng, Li Du, Lin Zhang, Fengjun Xiao","doi":"10.1186/s13287-025-04695-7","DOIUrl":"https://doi.org/10.1186/s13287-025-04695-7","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) exhibit therapeutic potential for ulcerative colitis (UC) due to their immunomodulatory, homing, and tissue repair capabilities, but clinical efficacy is constrained by heterogeneity. Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) exhibit superior stem cell properties compared to traditional MSCs, with CD146+ MSCs exhibiting enhanced biological characteristics. Nevertheless, the biological properties of CD146+iMSCs, as well as their therapeutic potential in UC, remain unclear.</p><p><strong>Methods: </strong>CD146+ subpopulations were isolated from iMSCs and umbilical cord-derived MSCs (UCMSCs) using magnetic beads sorting. The surface markers, proliferation capacity, differentiation potential, and regulatory effects on macrophage polarization were analyzed. Dextran sulfate sodium (DSS) - induced UC mouse models were established and treated with CD146+iMSCs. Body weight, disease activity index (DAI), colon length, and histopathological damage were evaluated. Peripheral immune cells and cytokines were analyzed by flow cytometry and ELISA. Transcriptome sequencing of colon tissues was performed and jointly analyzed with GEO datasets to identify the mechanisms of CD146+iMSCs' therapeutic efficacy in UC through differential gene expression profiling, protein-protein interaction network, functional enrichment analysis, and immune infiltration assessment. The core mechanisms were validated in vitro and vivo.</p><p><strong>Results: </strong>CD146+ iMSCs exhibited similar morphology and macrophage polarization regulatory capacity to CD146+UCMSCs, with superior proliferation and differentiation potential. CD146+ iMSCs significantly ameliorated UC symptoms (weight, DAI), reduced colon damage, decreased IL-6/TNF-α, and restored immune balance. Integrated analysis of colon transcriptome sequencing data and GEO datasets revealed the pivotal role of the IL-17 signaling pathway in the therapeutic effects of CD146+iMSCs. CD146+iMSCs effectively suppressed IL-17 expression both in cell inflammation models and colon tissues, downregulated nine hub genes, and inhibited macrophage polarization via the cGAS-STING axis.</p><p><strong>Conclusion: </strong>CD146+iMSCs exhibited advantages in proliferative and differentiation capabilities. They could ameliorate UC by suppressing IL-17 expression, downregulating HUB genes, and modulating macrophage polarization through the cGAS-STING axis.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"564"},"PeriodicalIF":7.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanical isolation of stromal vascular fraction from adipose tissue: methods and cellular outcomes: a systematic review and meta-analysis. 从脂肪组织中机械分离基质血管部分:方法和细胞结果:系统回顾和荟萃分析。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-14 DOI: 10.1186/s13287-025-04641-7
Marcos Sforza, Olga Ivanenko, Nazanin Biabani, Lara Sforza, Deepak M Kalaskar, Zahra Mohri, Afshin Mosahebi
{"title":"Mechanical isolation of stromal vascular fraction from adipose tissue: methods and cellular outcomes: a systematic review and meta-analysis.","authors":"Marcos Sforza, Olga Ivanenko, Nazanin Biabani, Lara Sforza, Deepak M Kalaskar, Zahra Mohri, Afshin Mosahebi","doi":"10.1186/s13287-025-04641-7","DOIUrl":"https://doi.org/10.1186/s13287-025-04641-7","url":null,"abstract":"<p><strong>Background: </strong>Stromal vascular fraction (SVF) from adipose tissue is a rich and accessible source of regenerative cells, including adipose-derived stem cells (ADSCs). SVF is most commonly isolated from lipoaspirate via enzymatic digestion, a process that is costly and considered 'more than minimal manipulation' by the United States Food and Drug Administration. In contrast, mechanically based isolation techniques have gained attention as a simpler, faster, and regulatory-compliant alternative, making them increasingly appealing for clinical applications.</p><p><strong>Main text: </strong>This systematic review and meta-analysis aimed to evaluate the outcomes of mechanical methods for harvesting SVF from human adipose tissue. Key parameters assessed included cell yield, viability, surface marker expression, and differentiation capacity. Additionally, split-sample studies were analysed descriptively to compare mechanical and enzymatic isolation approaches, thereby reducing variability in tissue source and preparation. A narrative synthesis was performed for all eligible studies (k = 22), and a single-arm meta-analysis of pooled outcomes of mechanical protocols was conducted for total cell yield and expression of CD34, CD73, and CD105 markers, depending on data availability. Mechanical isolation approaches varied considerably, but most high-performing protocols involved dedicated devices or systems. Meta-analysis revealed a pooled mean SVF cell yield of 11.96 × 10<sup>4</sup> cells/ml. The pooled expression levels of CD105 (4.08%) and CD73 (11.63%) indicated the presence of ADSC-associated markers, while CD34 (8.70%) reflected vascular and hematopoietic progenitor subpopulations commonly found in SVF. Mechanically isolated SVF cells demonstrated retained viability (up to 98%) and multilineage differentiation capacity, supporting their potential in regenerative applications. Furthermore, the retention of immunomodulatory and migratory functions may facilitate the integration of transplanted cells into host tissue environments.</p><p><strong>Conclusion: </strong>Mechanical SVF isolation methods can demonstrate comparable cell viability and differentiation potential and may outperform enzymatic protocols in terms of ADSC content and some functional properties (migration, immunomodulation). The main drawback of mechanical approaches is relatively lower total cell yield. The emergence of specialised devices for mechanical SVF isolation represents a key trend in the field. Continued efforts towards methodology and reporting standardisation are required to improve reproducibility and clinical reliability.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"560"},"PeriodicalIF":7.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Secretome from human placenta-derived mesenchymal stem cells repairs mechanically induced meniscus injury in mice by activating the proliferation and suppressing the apoptosis of endogenous meniscus progenitor cells. 人胎盘源间充质干细胞分泌组通过激活内源性半月板祖细胞增殖和抑制细胞凋亡修复机械诱导的小鼠半月板损伤。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-14 DOI: 10.1186/s13287-025-04688-6
Wei-Heng Chen, Wei-Yu Lai, Duy-Cuong Le, Jui-Chien Hsing, Mai-Huong T Ngo, Cheng-Xiang Kao, Kang-Yun Fan, Gee-Way Lin, Thai-Yen Ling, Yung-Che Kuo, Yen-Hua Huang
{"title":"Secretome from human placenta-derived mesenchymal stem cells repairs mechanically induced meniscus injury in mice by activating the proliferation and suppressing the apoptosis of endogenous meniscus progenitor cells.","authors":"Wei-Heng Chen, Wei-Yu Lai, Duy-Cuong Le, Jui-Chien Hsing, Mai-Huong T Ngo, Cheng-Xiang Kao, Kang-Yun Fan, Gee-Way Lin, Thai-Yen Ling, Yung-Che Kuo, Yen-Hua Huang","doi":"10.1186/s13287-025-04688-6","DOIUrl":"https://doi.org/10.1186/s13287-025-04688-6","url":null,"abstract":"<p><strong>Background: </strong>Meniscus diseases present certain therapeutic limitations. Although meniscectomy is the primary treatment option for meniscus injury (MI), this approach may accelerate the development of osteoarthritis and other degenerative joint diseases, and its therapeutic efficacy remains controversial. While human mesenchymal stem cells (MSCs) have emerged as a promising treatment option for MI, particularly in promoting cell proliferation and preventing apoptosis, their effect on activating endogenous meniscus progenitor cells (MPCs) to ameliorate MI and the underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>The secretome was collected from human placenta-derived MSCs (pcMSCs). A cellular model of MI was established by challenging mouse MPCs with H<sub>2</sub>O<sub>2</sub>. Male C57BL/6 mouse model of MI was established by mechanically destabilizing the medial meniscus (DMM). Protein expression was analyzed through Western blotting, flow cytometry, and immunohistochemistry staining. After secretome administration, behavioral activity was assessed through gait analysis and rotarod tests. Key secretome factors were identified through cytokine arrays and microRNA (miRNA) analysis.</p><p><strong>Results: </strong>The pcMSC secretome significantly mitigated MI in both cellular and mouse models, as indicated by gait analysis (P < 0.05), rotarod tests (P < 0.01), histological analysis (safranin-O staining, P < 0.001), and immunohistochemical staining for apoptosis marker (Caspase-3) and MPC proliferation markers (Gli-1, Sca-1, and Ki67). Cytokine arrays revealed several factors associated with immunomodulation (MCP1 and MCP3), regeneration and angiogenesis (IGF-1, ANG, and VEGFA), osteogenesis (OPG and OPN), and extracellular matrix preservation (TIMP1 and TIMP2). Furthermore, exosomal miRNA analysis revealed target genes involved in endogenous stem cell activation (SUFU and RUNX2), apoptosis regulation (Caspase-3), anti-inflammatory responses (IL-1β, IL-6, and PTEN), ECM formation (TRAF6 and MMPs), anti-cartilage matrix degradation (mTOR, AKT2, AKT3, and COL10A1), and cell migration (ADAM family).</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first study demonstrating that the human pcMSC secretome promotes meniscus regeneration through activating endogenous meniscus progenitor cells both in vivo and in vitro. Our findings suggest that these regenerative effects are mediated by growth factors and exosomal miRNAs in the pcMSC secretome. The potential exosomal miRNAs effectively modulated ECM formation, anti-apoptosis, anti-inflammation, and anti-cartilage matrix degradation to mitigate MPCs injury. Overall, this study provides valuable insights into potential stem cell-derived secretome cell-free therapies for patients with exercise-induced meniscus injuries.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"565"},"PeriodicalIF":7.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cholesterol metabolism on stem cell fate determination: a frontier horizon. 胆固醇代谢对干细胞命运的决定:一个前沿领域。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-14 DOI: 10.1186/s13287-025-04687-7
Boyang Xu, Ling Li, Qian Wei, Yuli Wang, He Huang, Tao Pang, Zhijian Wei, Guoqing Zheng, Yue Li
{"title":"Cholesterol metabolism on stem cell fate determination: a frontier horizon.","authors":"Boyang Xu, Ling Li, Qian Wei, Yuli Wang, He Huang, Tao Pang, Zhijian Wei, Guoqing Zheng, Yue Li","doi":"10.1186/s13287-025-04687-7","DOIUrl":"https://doi.org/10.1186/s13287-025-04687-7","url":null,"abstract":"<p><p>Cholesterol, a key steroid in cell membranes and organelles, is vital for processes like migration and apoptosis, regulated by biosynthesis, uptake, and esterification. Its metabolism significantly impacts stem cell fate via pathways like AKT/FOXO1 and Notch, influencing proliferation, differentiation, and migration. Thus, cholesterol emerges as a promising therapeutic target. This review aims to shed light on the impact of cholesterol metabolism on stem cells and explores cholesterol-targeting drugs' potential in regenerative medicine. Our purpose is to elucidate cholesterol's role in stem cell function and guide therapeutic development.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"561"},"PeriodicalIF":7.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quantifying human pluripotent stem cell attributes with population balance modeling. 用种群平衡模型量化人类多能干细胞属性。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-14 DOI: 10.1186/s13287-025-04668-w
Aedan Brown, Demetrios M Stoukides, Emmanuel S Tzanakakis
{"title":"Quantifying human pluripotent stem cell attributes with population balance modeling.","authors":"Aedan Brown, Demetrios M Stoukides, Emmanuel S Tzanakakis","doi":"10.1186/s13287-025-04668-w","DOIUrl":"https://doi.org/10.1186/s13287-025-04668-w","url":null,"abstract":"<p><strong>Background: </strong>The manufacturing of stem cell-based therapeutics hinges on models linking product characteristics to bioprocess conditions and cellular physiology. Typical quantitative models of cellular systems rely on population-average properties but fail to inform about the state of the cells based on critical quality attributes. Frameworks capturing the inherent heterogeneous nature of isogenic stem cell populations depend on physiological state functions (PSFs), which represent distributions of rates of cellular content change, division and differentiation. Such modalities can offer invaluable biological insights and facilitate the robust biomanufacturing of stem cell products, but obtaining the PSFs presents significant challenges.</p><p><strong>Methods: </strong>Population balance equation (PBE) modeling was implemented to derive stem cell PSFs. Their extraction from experimental data requires the acquisition of relevant distributions for newborn and dividing cells. These subpopulations for human embryonic and induced pluripotent stem cells were identified and analyzed with multiplex flow cytometry. Solution of the PBE model featuring appropriate PSFs was achieved via interval-of-quiescence techniques.</p><p><strong>Results: </strong>Rate distributions of synthesis, division and differentiation of human stem cells are presented. These PSFs were calculated for the first time capitalizing on experimental analysis of stem cell ensembles, including mitotic and newborn cells. Here, the PSFs were linked to the pluripotency marker POU5F1 (OCT4) as a descriptor of hPSC state and they followed a similar unimodal distribution over the OCT4 cargo for the stem cell lines examined. Exogenous lactate, which decelerates growth without affecting pluripotency marker expression, suppressed the PSF range revealing notable differences across the stem cell lines. The findings also pointed to line-specific effects induced by stressors such as high extracellular lactate. Lastly, the derivation was demonstrated of PSFs based on intracellular NANOG utilizing the PSF distributions extracted for OCT4.</p><p><strong>Conclusions: </strong>The work provides a first account of the derivation of rate distributions - rather than population averages - of stem cell physiological properties including division and change in OCT4 content. This enables the implementation of modeling frameworks for the rigorous quantitative description of hPSC populations that is important for addressing fundamental biological questions about pluripotency and differentiation, and critical in the biomanufacturing of hPSC-based therapeutics.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"563"},"PeriodicalIF":7.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ROS-responsive 3D biological scaffold delivers hypoxia-primed extracellular vesicles for targeted modulation of neuroinflammation in intracerebral hemorrhage. ros响应的3D生物支架提供缺氧引发的细胞外囊泡,用于脑出血神经炎症的靶向调节。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-14 DOI: 10.1186/s13287-025-04691-x
Aobo Zhang, Dan Qiao, Ziyang Jia, Zhanzhan Zhang, Dongdong Yan, Chengrui Nan, Liqiang Liu, Yunpeng Shi
{"title":"ROS-responsive 3D biological scaffold delivers hypoxia-primed extracellular vesicles for targeted modulation of neuroinflammation in intracerebral hemorrhage.","authors":"Aobo Zhang, Dan Qiao, Ziyang Jia, Zhanzhan Zhang, Dongdong Yan, Chengrui Nan, Liqiang Liu, Yunpeng Shi","doi":"10.1186/s13287-025-04691-x","DOIUrl":"https://doi.org/10.1186/s13287-025-04691-x","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that paracrine mechanisms may underlie the therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (EVs) (hUCMSC-exos) in mitigating neuroinflammation following intracerebral hemorrhage (ICH). Hypoxic preconditioning enhances the paracrine efficacy of hUCMSC-exos. Building on prior studies [1, 2], we developed a ROS-responsive three-dimensional (3D) biological scaffold encapsulating hypoxia-primed EVs (Hypo-Exos) for sustained release under reactive oxygen species (ROS)-rich conditions.</p><p><strong>Methods: </strong>The 3D biological scaffold was fabricated via a thermoresponsive crosslinking strategy using gelatin methacrylate (GelMA), silk fibroin, and brain-derived decellularized extracellular matrix (dECM), functionalized with phenylboronic acid (PBA)-modified polyvinyl alcohol (PVA). Hypo-Exos, enriched with miR-146b via hypoxia-inducible factor-1α (HIF-1α) activation, were incorporated into the scaffold using advanced 3D bioprinting. Dual-luciferase reporter assays validated miR-146b targeting of the 3'UTR of COP1 (an E3 ubiquitin ligase). In a rat ICH model, the scaffold was implanted in situ. Neurological function, angiogenesis, neuroinflammation, and synaptic plasticity were evaluated at days 1, 4, 7, and 14.</p><p><strong>Results: </strong>The 3D biological scaffold enabled sustained delivery of Hypo-Exos, shifting microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, thereby attenuating neuroinflammation and neuronal damage. Mechanistically, miR-146b suppressed COP1 expression via post-transcriptional silencing, thereby attenuating NF-κB p65 signaling and downregulating pro-inflammatory cytokines.</p><p><strong>Conclusion: </strong>The ROS-responsive 3D biological scaffold -mediated delivery of Hypo-Exos modulates neuroinflammation through ubiquitination pathways, stabilizes the early-phase ICH microenvironment, and improves functional recovery. This platform represents a promising therapeutic strategy for ICH, offering dual advantages as a drug delivery system and a regenerative therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"566"},"PeriodicalIF":7.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
BMDMs in metabolic memory impair fracture healing in diabetes. 代谢记忆中的bmdm损害糖尿病骨折愈合。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-14 DOI: 10.1186/s13287-025-04677-9
Dong Zhang, Changjiang Liu, Ying Yuan, Junwei Su, Zheng Wang, Chao Jian, Aixi Yu
{"title":"BMDMs in metabolic memory impair fracture healing in diabetes.","authors":"Dong Zhang, Changjiang Liu, Ying Yuan, Junwei Su, Zheng Wang, Chao Jian, Aixi Yu","doi":"10.1186/s13287-025-04677-9","DOIUrl":"https://doi.org/10.1186/s13287-025-04677-9","url":null,"abstract":"<p><strong>Background: </strong>The risk of fractures nonunion and delayed union in diabetes mellitus remains elevated despite glucose-lowering therapies. We hypothesized that bone marrow-derived macrophages (BMDMs) can be induced in the status of metabolic memory and still impair fracture healing when hyperglycemia stimulus disappears.</p><p><strong>Methods: </strong>Diabetic mice were divided into control (Ctrl), diabetic (DM), and diabetic with glucose control (DM/GC) groups. Fracture healing was assessed by micro-CT and histology, evaluating callus volume, bone volume/total volume (BV/TV), and inflammatory markers. In vitro, bone marrow-derived macrophages (BMDMs) were exposed to high glucose (HG) for varying periods to simulate hyperglycemia-induced metabolic memory, followed by normalization. Pro-inflammatory cytokines and macrophage polarization (M1/M2) were assessed via ELISA and flow cytometry. Osteogenesis and angiogenesis were evaluated in co-culture assays. RNA-seq and ATAC-seq were performed to analyze gene expression and chromatin accessibility, focusing on inflammatory pathways and CEBPB.</p><p><strong>Results: </strong>All data show that BMDMs play a significant role in the sustained effects of hyperglycemia on fracture healing even after glucose normalization in diabetic animals. Hyperglycemia-induced metabolic memory in BMDMs resulted in increased pro-inflammatory cytokines and a higher proportion of M1 macrophages, which impaired osteogenesis and angiogenesis. The co-culture medium from BMDMs in metabolic memory conditions suppressed osteogenesis in BMSCs and angiogenesis in HUVECs. Integrated analysis of RNA-seq and ATAC-seq in BMDMs revealed that inflammatory pathways were upregulated, with CEBPB identified as a key factor. Silencing CEBPB reversed these adverse effects and enhanced fracture healing in a diabetic model.</p><p><strong>Conclusions: </strong>Our results demonstrate the reason why the glucose-lowering therapies is unsuccessful in reducing the risk of fractures nonunion and delayed union in patients with diabetes mellitus, and shed light on a new strategy for the disease.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"562"},"PeriodicalIF":7.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The transforming role of wharton's jelly mesenchymal stem cell-derived exosomes for diabetic foot ulcer healing: a randomized controlled clinical trial. 沃顿果冻间充质干细胞衍生外泌体在糖尿病足溃疡愈合中的转化作用:一项随机对照临床试验。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-13 DOI: 10.1186/s13287-025-04690-y
Mohamed S Kishta, A M Hafez, Tamer Hydara, Zeinab Hamed, Mohamed M Bahr, Ashraf A Shamaa, Ahmed N Abdallah
{"title":"The transforming role of wharton's jelly mesenchymal stem cell-derived exosomes for diabetic foot ulcer healing: a randomized controlled clinical trial.","authors":"Mohamed S Kishta, A M Hafez, Tamer Hydara, Zeinab Hamed, Mohamed M Bahr, Ashraf A Shamaa, Ahmed N Abdallah","doi":"10.1186/s13287-025-04690-y","DOIUrl":"https://doi.org/10.1186/s13287-025-04690-y","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs), which have high rates of recurrence, amputation, and death, are a significant complication in the therapy of diabetes. Chronic inflammation, vascular dysfunction, and peripheral neuropathy are the results of their etiology, which includes dysregulated glucose homeostasis. These elements contribute to the poor clinical outcomes of DFUs and their complexity. Exosomes, which are natural nanovesicles that promote intercellular communication by transporting functional molecular cargos such as proteins, lipids, and nucleic acids, are being investigated as novel treatment approaches for diabetic foot ulcers (DFUs). These exosomes present a viable therapy option for DFU because they can alter cellular functions and promote wound healing.</p><p><strong>Methods: </strong>To improve wound healing in patients with diabetic foot ulcers (DFUs), we assessed the safety and effectiveness of Wharton's jelly-derived mesenchymal stem cell (WJ-MSC) exosomes in this study. 110 individuals with persistent DFUs participated in our research. Three groups were randomly selected from among the participants. For 4 weeks, the first group got weekly topical application of WJ-MSC exosome along with standard of care (SOC); the second control group received SOC alone; and the third placebo group received SOC together with CMC (the exosome vehicle). While effectiveness outcomes comprised the rate of wound closure and the duration to full epithelialization, safety endpoints included the frequency of adverse events.</p><p><strong>Results: </strong>According to our study's findings, 53 patients (62%) had fully recovered by the end of the study, and the treated group had a significantly higher percentage of patients who had fully recovered than the control group. The treated group's mean time to fully recover was 6 weeks (range: 4-8 weeks), while the controls were 20 weeks (range: 12-28 weeks).</p><p><strong>Conclusions: </strong>Our research proved that MSC-Exos is a viable treatment option for DFUs. MSC-Exos provide a multimodal approach to improve wound healing outcomes in diabetes patients.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"559"},"PeriodicalIF":7.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: circ_0002456/FUS interaction inhibits NF-κB signaling to attenuate DNA damage and inflammatory responses in hDPSCs. 更正:circ_0002456/FUS相互作用抑制NF-κB信号,减轻hDPSCs的DNA损伤和炎症反应。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-13 DOI: 10.1186/s13287-025-04720-9
Liecong Lin, Huixian Dong, Feng Lai, Jingkun Zhang, Bingtao Wang, Xiaohui Lv, Li Lin, Kehuan Hong, Yuxuan Zhao, Qianzhou Jiang
{"title":"Correction: circ_0002456/FUS interaction inhibits NF-κB signaling to attenuate DNA damage and inflammatory responses in hDPSCs.","authors":"Liecong Lin, Huixian Dong, Feng Lai, Jingkun Zhang, Bingtao Wang, Xiaohui Lv, Li Lin, Kehuan Hong, Yuxuan Zhao, Qianzhou Jiang","doi":"10.1186/s13287-025-04720-9","DOIUrl":"https://doi.org/10.1186/s13287-025-04720-9","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"558"},"PeriodicalIF":7.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The crosstalk among macrophages, chondrocytes and mesenchymal stem cells in osteoarthritis: the role of extracellular vesicles. 骨关节炎中巨噬细胞、软骨细胞和间充质干细胞之间的相互作用:细胞外囊泡的作用。
IF 7.3 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-10-10 DOI: 10.1186/s13287-025-04659-x
Hui Kong, Jiale Zheng, Juanjuan Han, Xin Meng, Xinran Li, Xiaodong Wang, Xin-An Zhang
{"title":"The crosstalk among macrophages, chondrocytes and mesenchymal stem cells in osteoarthritis: the role of extracellular vesicles.","authors":"Hui Kong, Jiale Zheng, Juanjuan Han, Xin Meng, Xinran Li, Xiaodong Wang, Xin-An Zhang","doi":"10.1186/s13287-025-04659-x","DOIUrl":"10.1186/s13287-025-04659-x","url":null,"abstract":"<p><p>Osteoarthritis (OA), as a complex degenerative disease, involves the interaction among macrophages, chondrocytes and mesenchymal stem cells (MSCs) in its pathogenesis. In recent years, extracellular vesicles (EVs), as important mediators of intercellular communication, have attracted much attention due to their potential in tissue repair and immune regulation. This review explores the role of EVs in the treatment of OA, particularly their functions in the crosstalk among macrophages, chondrocytes and MSCs. EVs carry bioactive molecules such as miRNAs and proteins, and influence cell behavior by regulating cell signaling pathways and gene expression. In OA, EVs can promote chondrocyte proliferation, inhibit inflammation, promote cartilage repair, and regulate macrophage polarization. Additionally, EVs can also be used as drug delivery systems to enhance drug targeting and bioavailability. Despite the great potential of exosomes in the treatment of OA, there are still challenges in their extraction and purification, dose determination, and long-term safety assessment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"553"},"PeriodicalIF":7.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275892","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信