Stem Cell Research & Therapy最新文献

{"title":"Neural stem cell transplantation in progressive multiple sclerosis: STEMS study long-term outcomes.","authors":"Maria A Rocca, Angela Genchi, Matteo Azzimonti, Irene Gattuso, Elisabetta Pagani, Loredana Storelli, Paolo Vezzulli, Elena Brambilla, Roberto Santangelo, Raffaella Greco, Fabio Ciceri, Roberto Furlan, Lucia Moiola, Andrea Falini, Gianvito Martino, Massimo Filippi","doi":"10.1186/s13287-026-05148-5","DOIUrl":"10.1186/s13287-026-05148-5","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the long-term safety and potential neuroprotective effects of human fetal neural precursor cell transplantation in individuals with progressive multiple sclerosis.</p><p><strong>Methods: </strong>This retrospective observational study assessed long-term follow-up data (median 5.7 years) from participants in a first-in-human phase I trial (NCT03269071) investigating neural cell transplantation in progressive multiple sclerosis. Clinical and radiological available data were collected and compared to baseline values and reference populations.</p><p><strong>Results: </strong>Long-term follow-up data were available for 11 of 12 patients. No serious adverse events related to cell transplantation occurred, confirming long-term safety. Although physical disability progressed over time, cognition remained stable compared to baseline. Five patients developed new T2-hyperintense brain lesions without associated contrast enhancement. Long-term gray matter atrophy rates were lower than those observed during the initial two years post-transplantation. Rates of gray and white matter atrophy approximated those of age-matched healthy individuals and patients with early-stage multiple sclerosis, with a trend for a lower atrophy rate compared to a control cohort with progressive disease. These structural findings were consistent with stable levels of circulating biomarkers of neurodegeneration.</p><p><strong>Conclusions: </strong>The findings support the long-term safety of fetal neural cell transplantation in progressive multiple sclerosis. Although exploratory in nature, the stability of cognitive function, reduced brain atrophy, and consistent biomarker profiles support the hypothesis of a possible neuroprotective effect that warrants further investigation in a controlled clinical trial setting.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224637","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":"Efficient genome editing in ASC-derived porcine lung organoids via GFP-guided enrichment.","authors":"Beom-Jin Jeon, Byeongho Moon, Hyun-Sung Jang, Dong-Hyeok Kwon, Young-Lim Jeon, Kyeong-Hyeon Eom, Jae-Yoon Choi, Young-Chai Kim, Goo Jang","doi":"10.1186/s13287-026-05185-0","DOIUrl":"10.1186/s13287-026-05185-0","url":null,"abstract":"<p><strong>Background: </strong>Adult stem cell-derived organoids are invaluable tools for disease modeling and translational medicine owing to their tissue-specific correspondence. However, their complex three-dimensional structure and low genome-editing efficiency have posed significant challenges for functional genetic studies. To address these limitations, this study aimed to establish porcine lung organoid (PLOs) and to develop a robust, high-efficiency genome-editing platform by leveraging the high physiological and anatomical similarity between pigs and humans.</p><p><strong>Methods: </strong>PLOs were derived from lung tissues and characterized by immunofluorescence and immunohistochemistry analysis. To enhance genome-editing efficiency using CRISPR/Cas9 and prime editing, a GFP-guided enrichment strategy was used by co-targeting a GFP transgene and endogenous loci, followed by the selection of GFP-negative organoids. Clonal expansion from single organoids was performed to generate genetically homogenous lines. Genetic modifications were validated through cDNA sequencing and western blot analysis. Structural integrity was assessed using AlphaFold2 modeling, and functional changes were evaluated using the forskolin-induced swelling assay.</p><p><strong>Results: </strong>The established PLOs exhibited sustained self-renewal capacity and expression of surfactant protein C alongside both proximal epithelial and mesenchymal markers, reflecting a composite lung organoid identity. GFP-guided enrichment significantly enriched edited cells; the mutation ratio in the GFP-negative group was significantly higher than that in the GFP-positive group. This system successfully generated fully gene-edited clones with high genetic homogeneity, and effectively enriched for precisely edited organoids, even when applying complex modalities such as prime editing.</p><p><strong>Conclusions: </strong>The PLOs and genome-editing platform developed in this study provide a powerful resource for translational medicine. By enabling precise genetic manipulation in a model that closely mimics human lung physiology, this system offers an essential platform for recapitulating human lung pathologies, studying zoonotic infectious diseases, and validating the efficacy of gene therapies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224883","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":"Extracellular vesicles in osteoarthritis: pathological mechanisms, regenerative therapies and clinical translation.","authors":"Zi-Hao Ying, Xiao-Na Xiang, Jiang-Yin Zhang, Cheng-Qi He, Hong-Chen He","doi":"10.1186/s13287-026-05194-z","DOIUrl":"10.1186/s13287-026-05194-z","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common chronic degenerative joint disease that has severe impacts on quality of life and creates a substantial socioeconomic burden. Conventional therapeutic strategies primarily focused on alleviating symptoms such as pain and functional impairment, with limited efficacy and an inability to reverse the disease process. Over the past two decades, regenerative medicine has been developed rapidly. Extracellular vesicles (EVs) have garnered widespread attention and there has been an upsurge of research interest in their immunomodulatory and regenerative potential in OA. However, there remains a lack of up-to-date systematic elaboration on EVs in the pathogenesis, regenerative therapy, and clinical translation of OA. Therefore, this paper focuses on a search of the relevant literature in the past five years, revealing that EVs of multiple tissue origins in individuals work together to drive OA pathological process and various sources-derived EVs demonstrate obvious effects in ameliorating OA, with the related molecular mechanisms becoming increasingly in-depth and comprehensive. Although naturally sourced EVs have limitations in yield, cargo loading, bioavailability and so on, the application of engineering technology is expected to improve these defects, positioning minimally invasive, cell-free, targeted EV-based therapies as a promising approach. In this regard, breaking through the technical bottlenecks in EV manufacturing and establishing unified industry standards have raised stringent requirements for the further clinical translation of EVs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536388","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":"Consistent functional properties of MSC-exosomes from different batches revealed by comparative multi-omics, bioinformatics and functional tests.","authors":"Byong Seung Cho, Jun Ho Lee, Kyong-Oh Shin, Kyungho Park, Kyojin Lee, Ella Shin, Hyunju Lee, Healim Lee, Kyong-Su Park, Dae Hyun Ha, Jan Lötvall","doi":"10.1186/s13287-026-05104-3","DOIUrl":"https://doi.org/10.1186/s13287-026-05104-3","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stromal cell-derived exosomes (MSC-EXOs), also called Extracellular Vesicles (EVs), exhibit anti-inflammatory effects in various diseases and are being developed for clinical use. For instance, MSC-EXO promotes skin healing post-laser therapy and improves outcomes in severe COVID-19. Selecting an optimal cellular source is critical for the therapeutic development of MSC-EXO. It has been suggested that GMP-produced MSC-exosomes have slightly different molecular content. This study therefore aimed to compare adipose tissue-derived MSC-EXO (ASC-EXO) from three healthy donors, isolated and characterized under GMP conditions.</p><p><strong>Methods: </strong>Exosomes were analyzed by nano-tracking analysis (NTA), cryo-electron microscopy, tetraspanin profiling, and multi-omics (proteomics, lipidomics, small RNA sequencing), as well as bioinformatics. Functional assays quantified anti-inflammatory effects in RAW264.7 macrophages and collagen production by human dermal fibroblasts (HDF). In vivo efficacy of ASC-EXOs was evaluated in a house dust mite antigen-induced atopic dermatitis mouse model through histopathological evaluation of ear thickness and differential cell counting.</p><p><strong>Results: </strong>No significant batch differences were observed in ASC-EXO yield or characteristics. Omics analyses revealed minor variations in protein, lipid, and small RNA cargo among the three batches, but GO-term bioinformatics indicated highly similar functional profiles. IL-6 suppression in RAW264.7 cells and cell proliferation and collagen production by HDF were similar among the ASC-EXO batches. CD73 enzymatic activity was consistent among batches. In vivo, the ASC-EXOs reduced skin thickness and eosinophilia in an atopic dermatitis model, with similar effects among the batches.</p><p><strong>Conclusions: </strong>In summary, ASC-EXOs from all batches demonstrated comparable anti-inflammatory and collagen-modulating effects in vitro, and similar inhibition of atopic dermatitis signs in vivo. We suggest that biological efficacy combined with bioinformatics analysis should guide MSC-EXO therapeutic quality control assays. These findings support the development of ASC-EXOs for clinical applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550229","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}

{"title":"Neuroprotective effect of mesenchymal stem cell-derived miR-143-3p on dopaminergic neurons via the TLR3/NF-κB/p53 signaling pathway.","authors":"Jing Sun, Tian Wang, Chen Qiu, Tianwen Li, Peng Wang, Tatyana Matveeva, Tanner Boyd, Qingyuan Tang, Jun Xue, Lu Su, Hyemyung Seo, Yi Eve Sun, Tian-Lin Cheng, Jeffrey Schweitzer, Bin Song","doi":"10.1186/s13287-026-05186-z","DOIUrl":"10.1186/s13287-026-05186-z","url":null,"abstract":"<p><strong>Background: </strong>Transplantation of midbrain dopaminergic neurons (mDANs) derived from human pluripotent stem cells (hPSCs) represents a promising therapeutic approach for Parkinson's disease (PD), with several clinical trials currently in progress. However, the poor survival of grafted mDANs, in part due to inflammation triggered by surgical injury, poses significant challenges to both therapeutic efficacy and safety. In recent years, mesenchymal stem cells (MSCs) and their derivatives have played an important role in the field of stem cell therapy due to their easy accessibility and immunomodulatory properties. However, their potential role as an adjunct in cell therapy remains unclear. Therefore, this study aims to investigate the protective effects of conditioned medium (CM) derived from MSCs and the mechanisms of action by which it attenuates surgery-induced neuroinflammation and enhances the survival of transplanted mDANs.</p><p><strong>Methods: </strong>To mimic the neuroinflammatory response caused by the surgical aspect of cell transplantation, transplantation medium alone (i.e. without cells) was injected into the striatum of male NOD SCID mice. The anti-inflammatory effects of MSC-CM in vivo were evaluated by assessing the activation of microglia and expression levels of pro-inflammatory cytokines. Next, an in vitro cell death model was established using IFN-γ and TNF-α stimulation. The protective effects of MSC-CM against IFN-γ and TNF-α-induced inflammatory injury in mDANs were assessed using immunofluorescence staining and TUNEL assay. To identify the active components and underlying mechanisms for the protective effects of MSC-CM, inhibitory treatments, miRNA sequencing, dual-luciferase reporter assay, and subsequent validation by qPCR and Western blotting were performed. Finally, MSC-CM was administered intranasally into male NOD SCID mice following mDAN transplantation to evaluate its protective effects on the grafted mDANs in vivo.</p><p><strong>Results: </strong>MSC-CM suppressed neuroinflammation and significantly protected mDANs from inflammation-induced cell death via inhibition of TLR3/NF-κB/p53 signaling pathway in this model system. This protective effect was largely reproduced by treatment with a specific component of the MSC-CM, miR-143-3p. Overexpression of miR-143-3p further enhanced the protective effects and mechanisms of action of MSC-CM.</p><p><strong>Conclusions: </strong>This study demonstrates that MSC-CM or its component miR-143-3p exert protective effects on mDANs against inflammatory injury, primarily by inhibiting the TLR3/NFκB/p53 signaling pathway.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550239","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":"Miro1-mediated mitochondrial transfer boosts stem cell therapy for muscle atrophy via restoring mitochondrial homeostasis.","authors":"Fangling Zhao, Jingxin Fu, Linli Gao, Mengting Zhou, Yuhui Xia, Zexian Zhao, MengNa Yang, Jiahui He, Wei Zhu, Mengxiong Pan, Kaiming Liu","doi":"10.1186/s13287-026-05191-2","DOIUrl":"10.1186/s13287-026-05191-2","url":null,"abstract":"<p><p>Mitochondrial dysfunction underlies the major defect in muscle atrophy (characterized by the loss of skeletal muscle mass and function). Mesenchymal stem cells (MSCs), which can mediate mitochondrial transfer (MT) via tunneling nanotubes (TNTs), have been shown to exert therapeutic effects, yet the underlying mechanism remains unclear. Mitochondrial Rho GTPase 1 (Miro1) is crucial for regulating mitochondrial homeostasis; in this study, we aimed to investigate the roles of Miro1 and Milton in MSC-based therapy for muscle atrophy. Dexamethasone (DEX)-induced C2C12 cells and chronically aged mice were used as in vitro cellular and in vivo muscle atrophy models, respectively. In vitro experiments demonstrated that overexpression of Milton alone failed to enhance MT in DEX-induced C2C12 cells. Although Milton could promote the formation of TNTs, it was unable to drive mitochondrial movement along microtubules in the absence of Miro1.In contrast, Miro1 knockdown (MSCmiro1^Lo) significantly reduced MT in vivo, while Miro1 overexpression (MSCmiro1^Hi) improved mitochondrial morphology, increased muscle fiber count and cross-sectional area, upregulated the expression of type I/III collagen, and downregulated the expression of Atrogin1 and MURF1. Additionally, Miro1 overexpression ameliorated functional outcomes such as grip strength, running distance, and physical activity, and elevated the levels of proteins related to mitochondrial fusion, mitophagy, and biogenesis in damaged muscle cells. These findings indicate that Miro1 is a critical driver of MT, and Miro1-enhanced MT confers substantial in vivo therapeutic benefits. This study provides robust evidence supporting Miro1 as a potential target for the treatment of muscle atrophy-related disorders.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536352","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":"Regenerative potential of extracellular vesicles from endometrial mesenchymal stem cells for modulating fibrosis and wound healing.","authors":"Fang-Yu Lin, Xiao-Tong Tan, Chih-Ming Pan, Chien-Chu Huang, Wan-Ling Chiang, Che-Kai Chang, Wu-Chou Lin, Chiung-Yi Yeh, Yu-Chuan Lin, Ting-Hsun Lin, Der-Yang Cho, Shao-Chih Chiu","doi":"10.1186/s13287-026-05189-w","DOIUrl":"10.1186/s13287-026-05189-w","url":null,"abstract":"<p><strong>Background: </strong>Fibrotic scarring resulting from trauma, burns, or surgery affects over 100 million people annually and is associated with functional, aesthetic, and psychological burdens. Current treatments remain inadequate, highlighting the need for novel, effective, and cell-free therapeutic strategies. Extracellular vesicle-enriched preparations derived from human endometrial mesenchymal stem cells (eMSC-EV-enriched preparations) may possess regenerative and anti-fibrotic potential, yet their roles in scar modulation and underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>eMSCs were isolated from human endometrial biopsies and characterized via flow cytometry and differentiation assays. The eMSC-EV-enriched preparations were obtained from conditioned medium and verified by TEM, NTA, and Western blotting. Functional assays were conducted in NIH3T3 fibroblasts to assess proliferation, migration, and transwell invasion capacity. A full-thickness cutaneous wound model and a bleomycin-induced dermal fibrosis model were used in C57BL/6 mice to evaluate tissue repair and fibrosis attenuation. Histological and molecular analyses were performed to assess collagen deposition, fibrosis-associated markers, and related signaling pathways. The potential involvement of miR-125b-5p in Smad2-related signaling was explored.</p><p><strong>Results: </strong>The eMSC-EV-enriched preparations displayed characteristic vesicular morphology and marker expression. Compared with BMMSC-EV-enriched preparations, eMSC-EV-enriched preparations more effectively reduced fibroblast proliferation and migration, with decreased transwell invasion capacity in vitro. In vivo, the eMSC-EV-enriched preparations enhanced wound closure, reduced collagen deposition, and were associated with improved collagen organization and an increased number of appendage-like structures. Expression of α-SMA and collagen I and III was reduced in tissues treated with the eMSC-EV-enriched preparations. Furthermore, the preparations were associated with increased miR-125b-5p levels and decreased Smad2/p-Smad2 expression, suggesting involvement of the miR-125b-5p/Smad2 axis. In the bleomycin model, the eMSC-EV-enriched preparations attenuated dermal thickening and collagen accumulation during fibrosis induction.</p><p><strong>Conclusions: </strong>Our findings indicate that eMSC-EV-enriched preparations improve repair quality and attenuate fibrosis development, potentially through modulation of fibroblast activity and involvement of the miR-125b-5p/Smad2 signaling pathway. These findings support further investigation of eMSC-EV-enriched preparations as a cell-free strategy for improving tissue remodeling in fibrotic skin conditions.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497949","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":"SDF-1 loaded dECM patch improves cardiac function in rats after myocardial ischemia.","authors":"Jing Zhang, Wanqing Lin, Qian Li, Shiyu Cui, Xiang Bu, Xin Jiang, Aiqun Ma, Tingzhong Wang","doi":"10.1186/s13287-026-05188-x","DOIUrl":"10.1186/s13287-026-05188-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ischemic heart disease (IHD) remains a global health challenge, characterized by irreversible cardiomyocyte loss and pathological ventricular remodeling. Myocardial patches provide mechanical support for infarcted myocardium, but conventional biomaterials lack bioactive components to facilitate tissue regeneration. This study introduces a novel therapeutic strategy: a stromal cell-derived factor-1 (SDF-1)-loaded decellularized extracellular matrix (dECM) (SDF-dECM) patch addressing both biological and biomechanical deficiencies in myocardial repair.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Porcine left ventricular dECM was decellularized, and SDF-1 was loaded to fabricate the SDF-dECM patch. The patch's physicochemical properties, biocompatibility, and SDF-1 release profile were evaluated via hematoxylin and eosin/4',6-diamidino-2-phenylindole staining, scanning electron microscopy, cytotoxicity assay, and enzyme-linked immunosorbent assay (ELISA). Transwell assays determined the chemotactic effect of SDF-1 on bone marrow mesenchymal stem cells (BMMSCs) and optimal concentration. Uniaxial tensile testing assessed mechanical properties. A finite element method (FEM) model was established to evaluate the patch's mechanical support. In vivo, male Sprague-Dawley rats were randomly divided into four groups (n = 15 per group): Sham, myocardial infarction (MI), MI + dECM, and MI + SDF-dECM. Echocardiography, histochemical staining, and immunofluorescence staining were used to assess cardiac function, tissue morphology, BMMSCs homing, microvascular regeneration, and cardiomyocyte apoptosis. The paracrine mechanism of BMMSCs was evaluated via ELISA and functional assays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The SDF-dECM patch achieved successful decellularization, maintained a porous structure (50-150 μm pore size), exhibited favorable biphasic mechanical properties, and exhibited sustained SDF-1 release for 28 days. SDF-1 effectively induced BMMSCs migration via the SDF-1/CXCR4 axis, with 200 ng/mL as the optimal concentration. In vivo, the SDF-dECM patch significantly enhanced endogenous BMMSCs homing to the peri-infarct area, promoted peri-infarct microvascular regeneration, and inhibited cardiomyocyte apoptosis. BMMSCs-conditioned medium contained high levels of vascular endothelial growth factor and hepatocyte growth factor, exerting pro-angiogenic and anti-apoptotic effects. FEM simulations showed the patch reduced infarct zone wall stress and stress concentration. Echocardiography and histological analysis confirmed the SDF-dECM patch significantly improved cardiac function, reduced infarct size and alleviated myocardial fibrosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The dual-functional SDF-dECM patch integrates sustained SDF-1 delivery for endogenous BMMSCs mobilization and biomechanical support to mitigate ventricular remodeling. The synergy between biological activity and mechanical stabilization provides a promising therapeutic ","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497989","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":"Mitochondria: the key hub for hematopoietic stem cell homeostasis maintenance and fate determination.","authors":"Ran Xu, Yaowei Meng, Anyu Xu, Xiaoming Yang, Weiming Tian, Changyan Li","doi":"10.1186/s13287-026-05183-2","DOIUrl":"10.1186/s13287-026-05183-2","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) constitute the pivotal cellular subset sustaining long-term hematopoietic homeostasis, characterized by robust self‑renewal and multilineage differentiation potential. Under physiological conditions, HSCs undergo stepwise differentiation through rigorously controlled regulatory networks to produce a full repertoire of mature blood cells, fulfilling basal physiological demands. Upon exposure to stress or pathological insults (e.g., bone marrow niche dysregulation), HSCs rapidly activate emergency regenerative programs to reconstitute hematopoietic function and restore systemic homeostasis. As intracellular \"powerhouses\" and central hubs of metabolic regulation, mitochondria exert profound regulatory effects on HSCs fate determination. The dynamic balance of mitochondrial metabolism not only furnishes HSCs with sufficient bioenergy but also generates critical metabolic intermediates; meanwhile, the fine-tuning of oxidative stress and autophagic machinery ensures mitochondrial network integrity. These biological processes are intricately intertwined, forming a complex regulatory network that profoundly modulates HSCs self-renewal, lineage commitment, and long-term hematopoietic reconstitution potential. This review systematically dissects the multi-dimensional regulatory mechanisms by which mitochondria govern HSCs, elaborates on the synergistic interactions and antagonistic effects among distinct components of the regulatory circuitry, and defines the pivotal role of mitochondria in sustaining HSCs homeostasis and orchestrating their repair responses to cellular damage. This work establishes a novel theoretical framework for devising mitochondrial-targeted interventions to sustain metabolic homeostasis in HSCs. Furthermore, it lays a solid scientific foundation for the treatment of hematological diseases and the development of precision therapeutic strategies, offering new insights into the clinical management of hematopoietic disorders.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472816","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":"Low frequency sinusoidal electromagnetic field accelerating intervertebral fusion through YAP/β-catenin axis.","authors":"Guangzi Chen, A Chunpin, Tao Xu, Jian Li, Weigang Li, Delu Zeng, Li Huang, Xuan Fang, Gaohong Sheng, Hongqi Zhao, Chaoxu Liu","doi":"10.1186/s13287-026-05137-8","DOIUrl":"10.1186/s13287-026-05137-8","url":null,"abstract":"<p><strong>Objective: </strong>Lumbar interbody fusion plays a crucial role in treating lumbar degenerative diseases, but its fusion rate is influenced by various factors. As a non-invasive physical therapy, low-frequency sinusoidal electromagnetic fields have been proven to promote bone tissue regeneration, although the specific molecular mechanisms remain incompletely understood. The aim of this study is to investigate whether low-frequency sinusoidal electromagnetic fields (LF-SEMF) can regulate the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts through YAP/β-catenin axis in vitro, and to evaluate the effect of LF-SEMF in assisting HA/Col I composite scaffold loaded with BMSCs in intervertebral fusion.</p><p><strong>Methods: </strong>The impact of LF-SEMF on osteogenic differentiation and mineralization was studied using BMSCs through alkaline phosphatase (ALP) staining and Alizarin red staining. Techniques such as Western blot, immunofluorescence, and qRT-PCR were employed to detect the impact of LF-SEMF on the YAP/β-catenin signaling pathway and related osteogenic genes. Gene silencing was performed to validate the critical role of the YAP/β-catenin axis in the promotion of osteogenic differentiation by LF-SEMF. A rat intervertebral fusion model was established, and the effects of LF-SEMF on intervertebral fusion were evaluated using imaging techniques (X-ray, Micro-CT) and histological analysis (HE staining, Masson staining, and immunohistochemical staining).</p><p><strong>Results: </strong>In vitro experiments demonstrated that exposure to LF-SEMF could facilitate the osteogenic differentiation of BMSCs, significantly upregulating the protein expression levels of YAP and β-catenin, and enhancing the expression of osteogenesis-related genes. Gene silencing experiments confirmed that the YAP/β-catenin axis played a critical role in the promotion of osteogenic differentiation by LF-SEMF. Additionally, animal studies showed that LF-SEMF could significantly promote new bone formation and increase bone strength in the fusion region of caudal vertebrae, while inhibition of YAP/β-catenin signaling pathway attenuated the fusion effect.</p><p><strong>Conclusions: </strong>LF-SEMF promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts through YAP/β-catenin signaling pathway. The hydroxyapatite/collagen I composite scaffold loaded with bone marrow mesenchymal stem cells can effectively improve the fusion effect of caudal vertebral fusion by LF-SEMF.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472822","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}