Stem Cell Research & Therapy最新文献

{"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}

{"title":"Lipid droplet-free nanovesicles extruded from stromal vascular fraction improve adipocyte regeneration in the centre of dermal graft.","authors":"Yuyang Zeng, Di Sun, Rongrong Wang, Ran An, Jiaming Sun, Jie Yang","doi":"10.1186/s13287-025-04240-6","DOIUrl":"10.1186/s13287-025-04240-6","url":null,"abstract":"<p><strong>Background: </strong>The stromal vascular fraction (SVF) has been validated for enhancing tissue regeneration because of its concentration of multipotent cells and growth factors, and for mitigating inflammatory response due to its elimination of the majority of lipid droplets. However, it is difficult for fresh SVF to maintain bioactivity for a long period, and the loss of numerous tangible masses during preparation limits its application in repairing large volume defects. Here, we fabricated a self-assembly nanovesicle extruded from SVF (SVF-EVs) by mechanical shear and co-transplanted it with dermal microparticles to verify its potential for repairing large volume defects.</p><p><strong>Methods: </strong>The SVF-EVs were prepared by removing the oil from adipose tissue followed by sequentially extruding SVF through membrane filters. The lipid content of SVF-EVs was compared with SVF using Oil Red O staining. The morphology and adipogenic-related protein of SVF-EVs were characterized. The pro-adipogenic potency of SVF-EVs in vitro was determined using Oil Red O staining of ADSCs, western blot, and qRT-PCR. In vivo, dermal particle grafts mixed with SVF-EVs were subcutaneously transplanted in nude mice and harvested after 4 and 6 weeks. By examining the weight and volume of grafts and histological staining, we explored the effect of SVF-EVs on adipose tissue regeneration and anti-inflammatory ability.</p><p><strong>Results: </strong>Our results showed that the removal rate of proceeding of SVF-EVs could remove 75.07 ± 2.80% lipid in SVF. The SVF-EVs displayed 100 ~ 150 nm sphere vesicles and contained pro-adipogenic protein. In vitro, SVF-EVs promote the synthesis of lipids in ADSCs. Besides, after co-transplanting of SVF-EVs, adipose regeneration was detected in vivo in the dermal particle grafts.</p><p><strong>Conclusions: </strong>These findings revealed that extruding SVF into nanovesicles can effectively reduce the implantation of lipid droplets that cause inflammation, and co-transplanting SVF-EVs with dermal microparticles may be a considerable strategy for large volume defects repair.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"114"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-derived stem cells attenuate rheumatoid arthritis by restoring CX₃CR1⁺ synovial lining macrophage barrier.","authors":"Lei Wang, Ming Hao, Yongyue Xu, Zhaoyan Wang, Hanqi Xie, Bo Zhang, Xue Zhang, Jun Lin, Xiaodan Sun, Jianbin Wang, Qiong Wu","doi":"10.1186/s13287-025-04144-5","DOIUrl":"10.1186/s13287-025-04144-5","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disease and the integrity of CX₃CR1⁺ synovial macrophage barrier significantly impacts its progression. However, the mechanisms driving the dynamic changes of this macrophage barrier remain unclear. Traditional drug therapies for RA have substantial limitations. Mesenchymal stem cells (MSCs)-based cell therapy, especially adipose-derived stem cells (ADSCs), hold therapeutic promise. Nevertheless, the underlying therapeutic mechanism of ADSCs, especially their interactions with CX₃CR1⁺ macrophages, require further investigation.</p><p><strong>Methods: </strong>To explore the interaction between ADSCs and CX₃CR1⁺ synovial macrophages during barrier reconstruction, underlying the therapeutic mechanism of ADSCs and the mechanisms on the dynamic changes of the macrophage barrier, scRNA-seq analysis was conducted 4 days after ADSCs injection in serum transfer-induced arthritis model mice. The roles of mitochondria transfer and ADSCs transplantation were also explored. Bulk RNA-seq analysis was performed after the co-culture of ADSCs and CX₃CR1⁺ synovial macrophages. To study the in vivo fate of ADSCs, bulk RNA-seq was performed on ADSCs retrieved at 0, 2, 4, and 7 days post-injection.</p><p><strong>Results: </strong>Intra-articular injection of ADSCs effectively attenuated the pathological progression of mice with serum transfer-induced arthritis. ADSCs gradually adhered to CX₃CR1⁺ macrophages, facilitating the restore of the macrophage barrier, while the absence of this barrier greatly weakened the therapeutic effect of ADSCs. scRNA-seq analysis revealed an Atf3^high Ccl3^high subset of CX₃CR1⁺ macrophages with impaired oxidative phosphorylation that increased during RA progression. ADSCs-mediated reduction of this subset appeared to be linked to mitochondrial transfer, and transplantation of isolated ADSCs-derived mitochondria also proved effective in treating RA. Both bulk RNA-seq and scRNA-seq analyses revealed multiple interaction mechanisms between ADSCs and CX₃CR1⁺ macrophages, including Cd74/Mif axis and GAS6/MERTK axis, which contribute to barrier restoration and therapeutic effects. Furthermore, bulk RNA-seq analysis showed that ADSCs primarily contribute to tissue repair and immune regulation subsequently.</p><p><strong>Conclusions: </strong>Our results suggest that ADSCs ameliorated the energy metabolism signature of CX₃CR1⁺ lining macrophages and may promote barrier restoration through mitochondria transfer. In addition, we elucidated the fate of ADSCs and the therapeutic potential of mitochondria in RA treatment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"111"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557717","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":"Exosomal miR-125b-5p derived from mesenchymal stromal/stem cell enhances anti-PD-1 therapy in mouse colon cancer model.","authors":"Mengmeng Jiang, Jia Liu, Shengquan Hu, Xueqin Yan, Yongkai Cao, Zhengzhi Wu","doi":"10.1186/s13287-025-04227-3","DOIUrl":"10.1186/s13287-025-04227-3","url":null,"abstract":"<p><strong>Background: </strong>There is compelling evidence that FoxP3⁺ regulatory T cells (Tregs) play a critical role in promoting tumor immune evasion. Our prior research demonstrated that the expression of miR-125b-5p directly inhibits Tregs by targeting TNFR2 and FoxP3. Given the significant therapeutic potential of mesenchymal stromal/stem cell (MSC)-derived exosomes (MSC-EXO) in cancer treatment, the potential role of MSC-EXO in augmenting anti-tumor immunotherapy through the delivery of miR-125b-5p remains unexplored.</p><p><strong>Methods: </strong>Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were employed to characterize exosomes derived from MSCs. Flow cytometry analysis was conducted to investigate the function of exosomal miR-125b-5p both in vitro and in vivo. Mouse MC38 tumor models were administrated MSC-derived exosomes containing miR-125b-5p via tail vein injection, with or without the concurrent injection (intraperitoneally, i.p.) of anti-PD-1 antibodies.</p><p><strong>Results: </strong>Our results indicated that exosomal miR-125b-5p derived from MSC significantly inhibited the expansion, proliferation and suppressive function of Tregs in vitro. Moreover, we observed a marked reduction in tumor growth in mice treated with exosomal miR-125b-5p. Notably, while anti-PD-1 therapy alone achieved a cure rate of approximately 30% in a mouse model of colon cancer, the combined administration of exosomal miR-125b-5p significantly enhanced the therapeutic efficacy, resulting in a more than two- to three-fold increase in tumor regression in approximately 80% of the treated mice. The underlying cellular mechanism was closely associated with the reduction of tumor-infiltrating Tregs. and the increase of CD8⁺ cytotoxic T lymphocytes (CTLs).</p><p><strong>Conclusions: </strong>In summary, our findings suggest that exosomal miR-125b-5p derived from MSC exerts prominent potential in advancing anti-PD-1 therapy by modulating tumor immune environment. This property of miR-125b-5p may be therapeutically harnessed in human cancers to enhance the efficacy of immunotherapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"112"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557877","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":"Apoptotic vesicles derived from bone marrow mesenchymal stem cells increase angiogenesis in a hind limb ischemia model via the NAMPT/SIRT1/FOXO1 axis.","authors":"Jinxing Chen, Zekun Shen, Bingyi Chen, Shuang Liu, Yifan Mei, Kai Li, Ziyang Peng, Chaoshuai Feng, Weiyi Wang, Shaoying Lu","doi":"10.1186/s13287-025-04245-1","DOIUrl":"10.1186/s13287-025-04245-1","url":null,"abstract":"<p><strong>Background: </strong>Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, the harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular vesicles produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, and gas neurotransmitters. ApoVs play significant roles in anti-inflammatory responses, anti-tumor activities, and tissue regeneration through intercellular communication, and they have demonstrated potential as drug carriers. In this study, we investigated the potential of bone marrow stem cell (BMSC)-derived ApoVs for treating CLTI.</p><p><strong>Methods: </strong>In vivo, we explored the therapeutic effect of ApoVs on a hindlimb ischemia model through Laser Doppler, matrigel plug assay, and histological analysis. In vitro, we analyzed the effects of ApoVs on the proliferation, migration, and angiogenesis of HUVECs and explored the uptake process of ApoVs. In addition, Proteomic analysis, western blotting, quantitative real-time PCR, shRNA, and siRNA were used to analyze ApoVs-induced HUVECs activation and downstream signaling pathways.</p><p><strong>Results: </strong>BMSCs transplantation showed improvement in a hind limb ischemia model, and this effect still exists after apoptosis of BMSCs. Subsequently, ApoVs of BMSCs were isolated and found to improve mouse hind limb ischemia in vivo. In vitro, ApoVs can be ingested by HUVECs through dynamin-, clathrin-, and caveolin-mediated endocytosis and promote its proliferation, migration, and angiogenesis. Mechanistically, ApoVs transferred NAMPT to HUVECs, therefore activating the NAMPT/SIRT1/FOXO1 axis, influencing the transcriptional activity of FOXO1, and promoting angiogenesis.</p><p><strong>Conclusions: </strong>Our results demonstrate that the transplanted BMSCs can ameliorate hindlimb ischemia by releasing ApoVs during apoptosis. The main mechanism of this effect is promoting the proliferation, migration, and angiogenesis of HUVECs through the NAMPT/SIRT1/FOXO1 axis. This study provides different insights into the therapeutic mechanisms through BMSCs and suggests a promising direction for ApoVs transplantation.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"105"},"PeriodicalIF":7.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537679","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}