Stem Cell Research & Therapy最新文献

{"title":"Effects and mechanisms of breastmilk stem cells in the treatment of white matter injury in newborn rats.","authors":"Meng Zhang, Haoran Wang, Yang He, Wenxing Li, Hongju Chen, Xinyu Zhang, Qiang Chen, Chao Yang, Maowen Luo, Bo Zhang, Jun Tang, Dezhi Mu","doi":"10.1186/s13287-025-04257-x","DOIUrl":"10.1186/s13287-025-04257-x","url":null,"abstract":"<p><strong>Background: </strong>Breastmilk stem cells (BSCs) have been reported to have potential benefits for infants. However, whether the BSCs could improve brain injury is unknown. A culture system for BSCs was established, and the roles of BSCs in treating white matter injury (WMI) were investigated in our study.</p><p><strong>Methods: </strong>Breastmilk samples were collected from healthy lactating women between days 1 and 5 after delivery. The BSCs were cultured in a specialized culture medium and then characterized through flow cytometry and immunofluorescence methods. A rat model with WMI was established by ligating the right carotid artery of Sprague-Dawley rats at postnatal day 3 (P3) and exposing the rats to 6% hypoxia for 2 h. Rats were categorized into sham, WMI with breastmilk cell (WMI + BC), and WMI with (WMI + NS) groups. In the WMI + BC group, 5 µL BCs (1 × 10⁶) was injected into the lateral ventricle 24 h post-modeling. Four different stages of oligodendrocyte (OL) markers were observed. Long-term neurobehavioral evaluations were conducted using the Morris water maze test. The inflammatory cytokines and proportion of proinflammatory microglial cells were detected to study the mechanisms of BSC treatment.</p><p><strong>Results: </strong>The isolated BSCs expressed mesenchymal stem cell-positive markers, including CD105, CD73, CD29, CD166, CD44, and CD90. Meanwhile, the mesenchymal stem cell-negative markers, including HLA-DR, CD45, and CD79a, were also found in BSCs. The BSCs did not express pluripotent stem cell markers, including SOX2, Nanog, OCT4, SSEA4, and TRA-1-60. Immunofluorescence detection showed that BSCs expressed neural stem/progenitor cell markers, including Vimentin, Nestin, and A2B5. Following BSC treatment, pathological improvements were observed in WMI. The expressions of mature OLs markers myelin basic protein and myelin-associated glycoprotein were increased in the corpus callosum and periventricular areas. Meanwhile, the numbers of myelin sheath increased, and learning and memory abilities improved. Furthermore, a decrease in B7-2+/Iba1 + proinflammatory microglia and an increase in CD206+/Iba1 + anti-inflammatory microglia were observed. The mRNA expressions of proinflammatory factors (Il1b, Il6, Ifng, and Tnfa) and anti-inflammatory factors (Arg1 and Tgfb) decreased and increased, respectively.</p><p><strong>Conclusion: </strong>Our findings suggest that BSCs can improve the maturation of OLs following WMI in newborn rats. The mechanisms may be attributed to the reduced proinflammatory microglia cells and factors as well as the increased anti-inflammatory microglia cells and factors.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"124"},"PeriodicalIF":7.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587067","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":"First-in-human clinical study of an embryonic stem cell product for urea cycle disorders.","authors":"Akihiro Umezawa, Akinari Fukuda, Reiko Horikawa, Hajime Uchida, Shin Enosawa, Yoshie Oishi, Naoko Nakamura, Kengo Sasaki, Yusuke Yanagi, Seiichi Shimizu, Toshimasa Nakao, Tasuku Kodama, Seisuke Sakamoto, Itaru Hayakawa, Saeko Akiyama, Noriaki Saku, Shoko Miyata, Kenta Ite, Palaksha Kanive Javaregowda, Masashi Toyoda, Hidenori Nonaka, Kazuaki Nakamura, Yoshikazu Ito, Yasuyuki Fukuhara, Osamu Miyazaki, Shunsuke Nosaka, Kazuhiko Nakabayashi, Chizuko Haga, Takako Yoshioka, Akira Masuda, Takashi Ohkura, Mayu Yamazaki-Inoue, Masakazu Machida, Rie Abutani-Sakamoto, Shoko Miyajima, Hidenori Akutsu, Yoichi Matsubara, Takashi Igarashi, Mureo Kasahara","doi":"10.1186/s13287-025-04162-3","DOIUrl":"10.1186/s13287-025-04162-3","url":null,"abstract":"<p><strong>Background: </strong>This study assesses the safety and efficacy of hepatocyte-like cell (HLC) infusion therapy derived from human embryonic stem cells as bridging therapy for neonatal-onset urea cycle disorders (UCD). The research includes both preclinical and clinical evaluations to determine the feasibility of HLC infusion as a therapeutic option for safer pediatric liver transplantation.</p><p><strong>Methods: </strong>Preclinical studies were conducted to validate the safety, biodistribution, and ammonia metabolism capabilities of HLCs using SCID mice models of UCD and extensive animal studies. In the clinical trial, five neonates with UCD received HLC infusions, intending to maintain metabolic stability and exceed a target weight of over 6 kg, which is considered necessary for safer liver transplantation.</p><p><strong>Results: </strong>Preclinical studies demonstrated that HLCs successfully engrafted in the liver without adverse migration or tumor formation and effectively elongated survival. Clinically, all five neonates exceeded the target weight of 6 kg while maintaining metabolic stability and successfully bridging to transplantation. Post-transplantation follow-up revealed stable growth, metabolic control, and no neurological complications.</p><p><strong>Conclusions: </strong>The combined preclinical and clinical findings support HLC infusion as a viable bridge therapy for neonates with UCD, providing metabolic support to achieve safer weight thresholds for transplantation. While promising, careful monitoring remains essential, particularly for potential complications such as thrombus formation.</p><p><strong>Trial registration: </strong>jRCT, jRCT1090220412. Registered on 27 February 2019, https://jrct.niph.go.jp/en-latest-detail/jRCT1090220412 (originally registered in JMACCT (JMA-IIA00412)).</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"120"},"PeriodicalIF":7.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573877","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 local pulsatile parathyroid hormone delivery system induces the osteogenic differentiation of dental pulp mesenchymal stem cells to reconstruct mandibular defects.","authors":"Yuanyuan Jia, Mianmian Duan, Yan Yang, Duchenhui Li, Dongxiang Wang, Zhenglong Tang","doi":"10.1186/s13287-025-04258-w","DOIUrl":"10.1186/s13287-025-04258-w","url":null,"abstract":"<p><strong>Background: </strong>Tumors and injuries often lead to large mandibular defects. Accelerating the osteogenesis of large bone defect areas is a major concern in current research. In this study, dental pulp mesenchymal stem cells (DPSCs) were used as seed cells, and the local pulsatile parathyroid hormone (PTH) delivery system was used as an osteogenic-inducing active ingredient to act on DPSCs and osteoblasts, which were applied to the jaw defect area to evaluate its therapeutic effect on bone regeneration.</p><p><strong>Methods: </strong>Pulsatile delivery systems, both with and without PTH, were developed following the protocols outlined in our previous study. In vitro, the biocompatibility of the pulsatile delivery system with DPSCs was assessed using the Cell Counting Kit-8 (CCK8) assay and live/dead cell staining. Osteogenic differentiation was evaluated through alkaline phosphatase staining and alizarin red staining. In vivo, critical bone defects with a diameter of 10 mm were created in the mandibles of white rabbits. The osteogenic effect was further assessed through gross observation, X-ray imaging, and histological examination.</p><p><strong>Results: </strong>In vitro experiments using CCK8 assays and live/dead cell staining demonstrated that DPSCs successfully adhered to the surface of the PTH pulsatile delivery system, showing no significant difference compared to the control group. Furthermore, alkaline phosphatase staining and Alizarin Red staining confirmed that the localized pulsatile parathyroid hormone delivery system effectively induced the differentiation of DPSCs into osteoblasts, leading to the secretion of abundant calcium nodules. Animal studies further revealed that the PTH pulsatile delivery system promoted the osteogenic differentiation of DPSCs, facilitating the repair of critical mandibular bone defects.</p><p><strong>Conclusion: </strong>The rhythmic release of PTH from the pulsatile delivery system effectively induces the osteogenic differentiation of DPSCs. By leveraging the synergistic interaction between PTH and DPSCs, this approach facilitates the repair of extensive mandibular bone defects.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"119"},"PeriodicalIF":7.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573892","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":"Cathepsin K inhibition promotes efficient differentiation of human embryonic stem cells to mature cardiomyocytes by mediating glucolipid metabolism and cellular energy homeostasis.","authors":"Ying Wang, Yang Cui, Xiaoyu Liu, Shengxian Liang, Li Zhong, Rui Guo","doi":"10.1186/s13287-025-04231-7","DOIUrl":"10.1186/s13287-025-04231-7","url":null,"abstract":"<p><strong>Background and aim: </strong>Generation of functional cardiomyocytes from human pluripotent stem cells (hPSCs) offers promising applications for cardiac regenerative medicine. Proper control of pluripotency and differentiation is vital for generating high-quality cardiomyocytes and repairing damaged myocardium. Cathepsin K, a lysosomal cysteine protease, is a potential target for cardiovascular disease treatment; however, its role in cardiomyocyte differentiation and regeneration is unclear. This study aims to investigate the effects and mechanisms of cathepsin K inhibition on the differentiation of human embryonic stem cell-induced cardiomyocytes (hESC-CMs) and myocardial generation.</p><p><strong>Methods: </strong>We cultured H9-hESCs in CDM3 medium to induce myocardial differentiation, adding cathepsin K inhibitor II (1 μM) on days 2, 5 and 8, respectively. Cells were observed and collected 48 h after each treatment. The morphology and contractile clusters of H9-hESCs were tracked with microscopy and video recording. Pluripotency and cardiac markers were assessed at each stage of differentiation. We also examined glucose and lipid metabolism, mitochondrion-related markers, apoptosis and autophagy.</p><p><strong>Results: </strong>CDM3 medium effectively differentiated high-density H9-hESCs into mature, spontaneously contracting cardiomyocytes. Cathepsin K inhibition accelerates the differentiation of H9-hESCs into cardiac mesoderm and cardiac precursor cells (CPCs) by reducing apoptosis, decreasing glycolysis and fatty acid metabolism at the early and middle stages, and subsequently facilitate the development and differentiation of cardiomyocytes by enhancing glucolipid metabolism and oxidative phosphorylation at the late stage. Meanwhile, cathepsin K inhibition enhanced mitochondrial function and lysosome-related gene transcription during the differentiation process.</p><p><strong>Conclusion: </strong>Our study highlights the potential of cathepsin K inhibition for renewable cardiomyocytes and suggests exploring metabolic pathways and signaling to improve cardiac regeneration and organoid development.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"118"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568212","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":"Advanced progress of adipose-derived stem cells-related biomaterials in maxillofacial regeneration.","authors":"Lijun Zhang, Zihang Yu, Shuchang Liu, Fan Liu, Shijie Zhou, Yuanyuan Zhang, Yulou Tian","doi":"10.1186/s13287-025-04191-y","DOIUrl":"10.1186/s13287-025-04191-y","url":null,"abstract":"<p><p>The tissue injury in maxillofacial region affects patients' physical function and specific mental health. This decade, utilizing regenerative medicine to achieve tissue regeneration has been proved a hopeful direction. Seed cells play a vital role in regeneration strategy. Among various kinds of stem cells that effectively to regenerate the soft and hard tissue of maxillofacial region, adipose-derived stem cells (ADSCs) have gained increasing interests of researchers due to their abundant sources, easy availability and multi-differentiation potentials in recent decades. Thus, this review focuses on the advances of ADSCs-based biomaterial in maxillofacial regeneration from the progress and strategies perspective. It is structured as introducing the properties of ADSCs, biomaterials (polymers, ceramics and metals) within ADSCs and the latest applications of ADSCs in maxillofacial regeneration, including temporomandibular joint (TMJ), bone, periodontal tissue, tooth, nerve as well as cosmetic field. In order to further facilitate ADSCs-based therapies as an emerging platform for regenerative medicine, this review also emphasized current challenges in translating ADSC-based therapies into clinical application and dissussed the strategies to solve these obstacles.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"110"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557873","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":"Preclinical study of engineering MSCs promoting diabetic wound healing and other inflammatory diseases through M2 polarization.","authors":"Di Wu, Rencun Liu, Xiaotong Cen, Wanwen Dong, Qing Chen, Jiali Lin, Xia Wang, Yixia Ling, Rui Mao, Haitao Sun, Rui Huang, Huanxing Su, Hongjie Xu, Dajiang Qin","doi":"10.1186/s13287-025-04248-y","DOIUrl":"10.1186/s13287-025-04248-y","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcer (DFU) represents a common and severe complication of diabetes mellitus. Effective and safe treatments need to be developed. Mesenchymal stem cells (MSCs) have demonstrated crucial roles in tissue regeneration, wound repair and inflammation regulation. However, the function is limited. The safety and efficacy of gene-modified MSCs is unknown. Therefore, this study aimed to investigate whether genetically modified MSCs with highly efficient expression of anti-inflammatory factors promote diabetic wound repair by regulating macrophage phenotype transition. This may provide a new approach to treating diabetic wound healing.</p><p><strong>Methods: </strong>In this study, human umbilical cord-derived MSCs (hUMSCs) were genetically modified using recombinant lentiviral vectors to simultaneously overexpress three anti-inflammatory factors, interleukin (IL)-4, IL-10, IL-13 (MSCs-3IL). Cell counting kit-8, flow cytometry and differentiation assay were used to detect the criteria of MSCs. Overexpression efficiency was evaluated using flow cytometry, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, and cell scratch assay. We also assessed MSCs-3IL's ability to modulate Raw264.7 macrophage phenotype using flow cytometry and quantitative real-time PCR. In addition, we evaluated diabetic wound healing through healing rate calculation, HE staining, Masson staining, and immunohistochemical analysis of PCNA, F4/80, CD31, CD86, CD206, IL-4, IL-10 and IL-13. In addition, we evaluated the safety of the MSCs-3IL cells and the effect of the cells on several other models of inflammation.</p><p><strong>Results: </strong>MSCs-3IL efficiently expressed high levels of IL-4 and IL-10 (mRNA transcription increased by 15,000-fold and 800,000-fold, protein secretion 400 and 200 ng/mL), and IL-13 (mRNA transcription increased by 950,000-fold, protein secretion 6 ng/mL). MSCs-3IL effectively induced phenotypic polarization of pro-inflammatory M1-like macrophages (M1) towards anti-inflammatory M2-like macrophages (M2). The enhancement of function does not change the cell phenotype. The dynamic distribution in vivo was normal and no karyotype variation and tumor risk was observed. In a mouse diabetic wound model, MSCs-3IL promoted diabetic wound healing with a wound closure rate exceeding 96% after 14 days of cell treatment. The healing process was aided by altering macrophage phenotype (reduced CD86 and increased CD206 expression) and accelerating re-epithelialization.</p><p><strong>Conclusions: </strong>In summary, our study demonstrates that genetically modified hUMSCs effectively overexpressed three key anti-inflammatory factors (IL-4, IL-10, IL-13). MSCs-3IL-based therapy enhances diabetic wound healing with high efficiency and safety. This suggests that genetically modified hUMSCs could be used as a novel therapeutic approach for DFU repair.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"113"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557946","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":"Purine metabolism in bone marrow microenvironment inhibits hematopoietic stem cell differentiation under microgravity.","authors":"Xiru Liu, Hao Zhang, Jinxiao Yan, Penghui Ye, Yanran Wang, Nu Zhang, Zhenhao Tian, Bin Liu, Hui Yang","doi":"10.1186/s13287-025-04213-9","DOIUrl":"10.1186/s13287-025-04213-9","url":null,"abstract":"<p><strong>Background: </strong>Spaceflight and microgravity environments have been shown to cause significant health impairments, including bone loss, immune dysfunction, and hematopoietic disorders. Hematopoietic stem cells (HSCs), as progenitors of the hematopoietic system, are critical for the continuous renewal and regulation of immune cells. Therefore, elucidating the regulatory mechanisms governing HSC fate and differentiation in microgravity environments is of paramount importance.</p><p><strong>Methods: </strong>In this study, hindlimb unloading (HU) was employed in mice to simulate microgravity conditions. After 28 days of HU, cells were isolated for analysis. Flow cytometry and colony-forming assays were utilized to assess changes in HSC proliferation and differentiation. Additionally, transcriptomic and untargeted metabolomic sequencing were performed to elucidate alterations in the metabolic pathways of the bone marrow microenvironment and their molecular regulatory effects on HSCs fate.</p><p><strong>Results: </strong>Our findings revealed that 28 days of HU impaired hematopoietic function, leading to multi-organ damage and hematological disorders. The simulated microgravity environment significantly increased the HSCs population in the bone marrow, particularly within the long-term and short-term subtypes, while severely compromising the differentiation capacity of hematopoietic stem/progenitor cells. Transcriptomic analysis of HSCs, combined with metabolomic profiling of bone marrow supernatants, identified 1,631 differentially expressed genes and 58 metabolites with altered abundance. Gene set enrichment analysis indicated that HU suppressed key pathways, including hematopoietic cell lineage and MAPK signaling. Furthermore, integrated analyses revealed that metabolites affected by HU, particularly hypoxanthine enriched in the purine metabolism pathway, were closely associated with hematopoietic cell lineage and MAPK signaling pathways. Molecular docking simulations and in vitro experiments confirmed that hypoxanthine interacts directly with core molecules within these pathways, influencing their expression.</p><p><strong>Conclusions: </strong>These findings demonstrate that hypoxanthine in the bone marrow supernatant acts as a signaling mediator under microgravity, influencing HSCs fate by modulating hematopoietic cell lineage and MAPK signaling pathways. This study offers novel insights into the impact of microgravity on HSC fate and gene expression, underscoring the pivotal role of bone marrow microenvironmental metabolic changes in regulating key signaling pathways that determine hematopoietic destiny.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"115"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557949","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 small extracellular vesicles reduced hepatic lipid accumulation in MASLD by suppressing mitochondrial fission.","authors":"Yifei Chen, Fuji Yang, Yanjin Wang, Yujie Shi, Likang Liu, Wei Luo, Jing Zhou, Yongmin Yan","doi":"10.1186/s13287-025-04228-2","DOIUrl":"10.1186/s13287-025-04228-2","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by lipid accumulation in liver cells. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have great potential in repairing and regenerating liver diseases. However, it is still unclear whether MSC-sEV can inhibit hepatocyte lipid accumulation by regulating mitochondrial fission.</p><p><strong>Methods: </strong>We investigated the effects of MSC-sEV on mitochondrial fission and its potential mechanism in lipotoxic hepatocytes and high-fat diet (HFD)-induced MASLD mice.</p><p><strong>Results: </strong>We found that MSC-sEV can effectively inhibit the expression of the Dynamin-related protein 1 (DRP1), thereby reducing mitochondrial fission, mitochondrial damage, and lipid deposition in lipotoxic hepatocytes and livers of HFD-induced MASLD in mice. Further mechanistic studies revealed that RING finger protein 31 (RNF31) played a crucial role in mediating the inhibitory effect of MSC-sEV on DRP1 and mitochondrial fission. RNF31 can suppress DRP1 expression and mitochondrial fission, thereby improving mitochondrial dysfunction and reducing hepatocyte lipid deposition. These findings suggest that MSC-sEV may downregulate hepatocyte DRP1-mediated mitochondrial fission by transporting RNF31, ultimately inhibiting hepatocyte lipid accumulation.</p><p><strong>Conclusions: </strong>The insights from this study provide a new perspective on the mechanism of MSC-sEV in reducing lipid accumulation and offer a potential therapeutic target by targeting DRP1 to inhibit hepatocyte steatosis and the progression of MASLD.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"116"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568217","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":"Single-cell transcriptomics of clinical grade adipose-derived regenerative cells reveals consistency between donors independent of gender and BMI.","authors":"Frederik Adam Bjerre, Jakob Vennike Nielsen, Mark Burton, Pratibha Dhumale, Mads Gustaf Jørgensen, Sabrina Toft Hansen, Lars Lund, Mads Thomassen, Jens Ahm Sørensen, Ditte Caroline Andersen, Charlotte Harken Jensen","doi":"10.1186/s13287-025-04234-4","DOIUrl":"10.1186/s13287-025-04234-4","url":null,"abstract":"<p><p>Adipose-derived regenerative cells (ADRCs) also referred to as the stromal vascular fraction, provide an ample source of stem cells with widespread regenerative therapeutic use. Being heterogenous in nature, possibly affecting the clinical outcome after stem cell treatment, the ADRC- donor, -BMI, and -gender may have a large impact on ADRC composition and quality but this remains largely unexplored. Herein, we provide a comprehensive single-cell RNA sequencing ADRC mapping across two cell trial intervention studies but found no gender- or BMI-related variations, except for a minor female increase in PI16/CD55-expressing stem cells. Indeed, ADRC heterogeneity was surprisingly minimal between donors. This provides important decision-making support on adipose stem cell donor selection for stem cell treatments, and suggest that donor, gender and BMI should be regarded as less influential.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"109"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557858","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":"Effects of intra-articular applied rat BMSCs expressing alpha-calcitonin gene-related peptide or substance P on osteoarthritis pathogenesis in a murine surgical osteoarthritis model.","authors":"Sabine Stöckl, Shahed Taheri, Verena Maier, Amir Asid, Martina Toelge, Hauke Clausen-Schaumann, Arndt Schilling, Susanne Grässel","doi":"10.1186/s13287-025-04155-2","DOIUrl":"10.1186/s13287-025-04155-2","url":null,"abstract":"<p><strong>Background: </strong>About 655 million persons worldwide are affected by osteoarthritis (OA). As no therapy modifies disease progression long-term, there is an immense clinical need for novel therapies. The joints are innervated by alpha calcitonin gene-related peptide (αCGRP)- and substance P (SP)-positive sensory nerve fibers. Both neuropeptides have trophic effects on target cells within the joints. The aim of this study was to examine the effects of SP- and αCGRP-expressing intra-articular (i.a.) applied rat(r)BMSC on cartilage and subchondral bone structural changes after OA induction.</p><p><strong>Methods: </strong>Mice were subjected to destabilization of the medial meniscus (DMM) surgery, followed by i.a. injections with rBMSC, transduced with lacZ, SP or αCGRP. 2, 8 and 16 weeks after DMM/Sham surgery, motion analysis and serum marker analysis were performed. Cartilage and subchondral bone properties were assessed by OA scoring, atomic force microscopy and nano-CT analysis.</p><p><strong>Results: </strong>OARSI scores of the medial cartilage compartments indicated induction and progression of OA after DMM surgery in all groups. Differences between the treatment groups were mostly restricted to the lateral cartilage compartments, where αCGRP caused a decrease of structural changes. DMM-rBMSC-αCGRP or -SP mice displayed decreased cartilage stiffness in the cartilage middle zone. DMM-rBMSC-αCGRP mice revealed improved mobility, whereas Sham-rBMSC-SP mice revealed reduced mobility compared to rBMSC-lacZ. With respect to condyle length, subarticular bone and ephiphyseal bone morphology, DMM-rBMSC-SP mice had more alterations indicating either a more progressed OA stage or a more severe OA pathology compared to controls. In addition, DMM-rBMSC-SP mice developed osteophytes already 8 weeks after surgery. Adiponectin serum level was increased in DMM-rBMSC-αCGRP mice, and MIP1b level in DMM-rBMSC-SP mice. Notably, pain and inflammation markers increased over time in rBMSC-SP mice while rBMSC-αCGRP mice revealed a bell-shaped curve with a peak at 8 weeks.</p><p><strong>Conclusions: </strong>We conclude that i.a. injection of rBMSC in general have a beneficial effect on cartilage matrix structure, subchondral bone microarchitecture and inflammation. rBMSC-αCGRP have anabolic and possible analgesic properties and may attenuate the progression or severity of OA. In contrast, rBMSC-SP exert a more catabolic influence on knee joints of both, Sham and DMM mice, making it a potential candidate for inhibition studies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"117"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568214","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}