Stem Cell Research & Therapy最新文献

{"title":"Single-cell transcriptome atlas reveals mitophagy dynamics in acute chemical injury model and the role of MSCs transplantation.","authors":"Sang Luo, Fang Wu, Xiaojun Yang","doi":"10.1186/s13287-025-04491-3","DOIUrl":"10.1186/s13287-025-04491-3","url":null,"abstract":"<p><strong>Background and purpose: </strong>Mitochondrial autophagy, also referred to as mitophagy, clears damaged mitochondria and has dual functions in disease development and liver homeostasis in response to liver pathologies. Mesenchymal stem/stromal cells (MSCs) are most commonly used to treat liver failure because they are easy to obtain and present no ethical problems. However, the molecular mechanisms by which MSCs promote liver failure progression are not fully understood. This study explored the distinct mitophagy states in hepatocytes and macrophages during MSCs therapy.</p><p><strong>Experimental approach: </strong>To investigate tissue-specific mitophagy in acute liver failure (ALF), we generated a single-cell transcriptome (scRNA-seq) atlas of liver tissue from healthy mice, ALF mice and human umbilical cord mesenchymal stem/stromal cell (hUC-MSC)-transplanted mice.</p><p><strong>Key results: </strong>The data revealed the complex cellular landscape of liver tissue during ALF progression, revealing alterations in metabolic fluxes and mitophagy activation. Through the intersection of single-cell sequencing data with mitophagy-related genes (MRGs), a total of 24 differentially expressed MRGs were identified. Gene Ontology (GO) analysis further revealed that the ubiquitinating enzyme Arih1 was significantly upregulated after MSC transplantation, whereas the mitophagy genes Bnip3L/NIX and Beciln1 were significantly downregulated in mononuclear phagocytes(MPs).</p><p><strong>Conclusions and implications: </strong>Our research demonstrated that during the development of ALF, mitophagy within hepatocytes is suppressed, whereas in MPs, mitophagy is excessively activated. MSCs are capable of alleviating disease progression by modulating the distinct mitophagy states of cells, providing an important resource for investigating mitophagy regulation in hepatic homeostasis and disease development.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"350"},"PeriodicalIF":7.1,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576316","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":"Novel sponge formulation of mesenchymal stem cell secretome and hyaluronic acid: a safe and effective topical therapy for Psoriasis vulgaris.","authors":"Estefanía Elgueta, Catalina P Prieto, Dan Hartmann, Daniela Carrillo, Natalie Edwards, Constanza Martínez, Dan Pérez, Bárbara Casas, Luis Vergara, Fernando Valenzuela, Verónica Catalán, José Lattus, Felipe Oyarzun-Ampuero, Verónica Palma","doi":"10.1186/s13287-025-04415-1","DOIUrl":"10.1186/s13287-025-04415-1","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis vulgaris is the most common form of psoriasis, yet current treatments often lead to significant side effects, resulting in a high rate of therapy desertion. Here, we explored a novel therapeutic approach using the secretome from Wharton Jelly-derived mesenchymal stem cells, biologically stabilized and enhanced with hyaluronic acid (HA), its presentation is an easy-to-apply topical sponge. This formulation had previously demonstrated efficacy in vitro and in experimental psoriasis mouse models.</p><p><strong>Methods: </strong>In vitro characterization studies included dynamic light scattering, nanoparticle tracking analysis, optical/electronic microscopy, microbiological experiments, and angiogenic capacity (HUVEC cells). In vivo studies included angiogenic capacity in chicken embryo chorioallantoic membrane (CAM), safety (hypersensitive and healthy volunteers), and efficacy (double-blinded and randomized patients).</p><p><strong>Results: </strong>We demonstrated the presence of spherical exosomes (164 ± 87 nm, PDI of 0.38, and 1.5 × 10⁷ particles/mL) within the selected secretomes, which exhibited significant proangiogenic activity in HUVEC cells and in a CAM assay. The secretome-containing sponges displayed distinct physicochemical properties, such as the absence of nitrogen and reduced carbon and oxygen content, resulting in a more cross-linked material with thinner fibers. These characteristics extended the dispersion time in aqueous media. Microbiological testing confirmed sterility in the packed, ready-to-use secretome-HA sponges after 3 months of storage. To assess safety, we selected doses (based on total protein content) that were applied to three patients with atopic dermatitis (42 µg of protein, patch test, 5 days) and four healthy volunteers (210 µg, 15 days) with no observed adverse topical or systemic effects. In a 30-day efficacy study, 12 patients with bilateral psoriasis exhibited up to a 33% reduction in mPASI scores and a 41% decrease in plaque size. Additionally, transepidermal water loss (TEWL) was reduced by up to 30%, while skin elasticity/flexibility improved by 43%.</p><p><strong>Conclusions: </strong>These findings suggest that the topical application of the secretome-HA sponge is a safe and effective therapeutic option for alleviating symptoms of psoriasis vulgaris.</p><p><strong>Trial registration: </strong>SSMN, SSMN047/2021. Registered 27 October 2021, https://www.ssmn.cl/comite_etica.php .</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"348"},"PeriodicalIF":7.1,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576315","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":"LPS pretreated dental follicle stem cell derived exosomes promote periodontal tissue regeneration via miR-184 and PPARα-Akt-JNK signaling pathway.","authors":"Liangrui Chen, Jiaxiang Zhang, Jialu Yu, Shujuan Guo, Weidong Tian","doi":"10.1186/s13287-025-04462-8","DOIUrl":"10.1186/s13287-025-04462-8","url":null,"abstract":"<p><strong>Purpose: </strong>Lipopolysaccharide (LPS) pretreated dental follicle stem cells (DFSCs)-derived exosomes (L-D-Exo) exhibit enhanced therapeutic effects in periodontitis treatment, but the effective components responsible for these effects remain unidentified. The aim of this study is to investigate the differences in expression profile and regulatory effect of the exosomal microRNAs (miRNAs) from DFSCs and PDLSCs on periodontal tissue regeneration.</p><p><strong>Methods: </strong>High-throughput miRNA sequencing was performed on DFSCs and PDLSCs derived exosomes under both Porphyromonas gingivalis (P.g) LPS pretreatment and normal conditions. Through bioinformatic analysis, miR-184 was selected as the key miRNA due to its specific down-regulation in L-D-Exo, which linked to oxidative stress regulation. After changing the expression of miR-184 in PDLSCs, the fluorescence intensity of reactive oxygen species (ROS), malondialdehyde (MDA) content and antioxidant related enzyme activities, and the expression levels of inflammatory cytokines and osteogenesis-related genes in PDLSCs were detected. In addition, dual-luciferase reporter assay and Western blot were used to explore the target gene and downstream signaling pathways. In vivo, miR-184 Antagomir was injected into mice with experimental periodontitis to evaluate the role and mechanism of miR-184 in periodontal tissue regeneration.</p><p><strong>Results: </strong>Inhibition of miR-184 in PDLSCs significantly impaired oxidative stress, as evidenced by decreased ROS fluorescence intensity and MDA content, alongside increased activities of antioxidant enzymes. This reduction in oxidative stress subsequently decreased the expression of intracellular inflammatory cytokines, while promoting the expression of osteogenic genes. The dual-luciferase reporter assay confirmed the direct binding of miR-184 with Peroxisome proliferator-activated receptor α (PPARα). MiR-184 inhibition activated the downstream protein kinase B (Akt) pathway and inhibited the c-Jun N-terminal kinase (JNK) pathway under inflammatory conditions. Furthermore, miR-184 Antagomir application also enhanced the therapeutic efficacy of periodontitis mice by reducing inflammation and promoting periodontal osteogenesis.</p><p><strong>Conclusion: </strong>Inhibition of miR-184 facilitates periodontal regeneration, which targets the PPARα-Akt-JNK signaling pathway to suppress oxidative stress in periodontal tissues.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"347"},"PeriodicalIF":7.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554912","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":"Interleukin-1 receptor antagonist overexpression in mesenchymal stem cells improves hemorrhagic cystitis outcomes via HtrA serine peptidase 3.","authors":"Jialin Song, Yanxiao Han, Yuyan Chen, Lin Cheng, Juan Xiao, Ai Li, Dexiao Kong, Yang Jiang, Chengyun Zheng","doi":"10.1186/s13287-025-04443-x","DOIUrl":"10.1186/s13287-025-04443-x","url":null,"abstract":"<p><strong>Background: </strong>Hemorrhagic cystitis (HC), a frequent complication of hematopoietic stem cell transplantation (HSCT), significantly affects quality of life and may worsen prognosis. Mesenchymal stem cells (MSCs) are known for their anti-inflammatory and tissue-regenerative properties. IL-1 receptor antagonist (IL-1Ra) blocks IL-1α and IL-1β by binding IL-1 receptors, offering potential therapeutic benefits. The aim of this study was to explore the therapeutic effect of MSCs overexpressing IL-1Ra on HC and investigate the underlying mechanisms.</p><p><strong>Methods: </strong>MSCs were isolated from human umbilical cord tissues, and IL-1Ra-overexpressing MSCs (oeIL-1Ra-MSCs) were generated using lentiviral transfections. HC was induced in rats by cyclophosphamide administration. Rats received tail vein injections of either oeIL-1Ra-MSCs or control MSCs (Mock-MSCs). Hematuria and bladder tissue changes were assessed using test strips and hematoxylin & eosin (HE) staining. Immunohistochemistry detected molecular changes in bladder tissues. Gene expression differences between the two MSC groups were analyzed by mRNA sequencing and ChIP techniques.</p><p><strong>Results: </strong>Treatment with oeIL-1Ra-MSCs significantly alleviated hematuria and reduced bladder edema and hemorrhage, and reduced mRNA expression levels of IL-1β, IL-6, and TNF-α in bladder tissues, compared with those in the Mock-MSC treatment group. Immunohistochemical staining showed a higher presence of CD105-positive cells (a marker for human MSCs) and CD31-positive vessels in bladder tissues treated with oeIL-1Ra-MSCs, indicating enhanced MSC migration and vascular stability. In vitro migration assay demonstrated a higher migration capacity of IL-1Ra overexpressing MSCs compared with that of control MSCs. Moreover, angiopoietin-1 (Ang-1) expression increased, while Angiopoietin-2 (Ang-2) expression decreased in bladder tissues treated with oeIL-1Ra-MSCs, suggesting enhanced blood vessel stabilization. Conditioned medium from oeIL-1Ra-MSC cultures stimulated human umbilical vein endothelial cell (hUVEC) migration, proliferation, and angiogenesis more effectively compared with that in control MSCs. mRNA sequencing revealed elevated HtrA3 expression in oeIL-1Ra-MSCs compared with that in control MSCs. Molecular analysis suggested that IL-1Ra overexpression in MSCs upregulated HtrA3 expression through inhibition of the JNK-c-Jun pathway and activation of the ERK-Egr-1 pathway.</p><p><strong>Conclusion: </strong>Overexpression of IL-1Ra significantly enhances the therapeutic efficacy of MSCs in HC by promoting MSC migration to damaged bladder tissues, suppressing inflammation, stabilizing blood vessels, and upregulating angiogenesis via activation of HtrA3 signaling pathways.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"337"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544934","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":"Causes and therapeutic limitations of clinical alopecia and the advent of human pluripotent stem cell follicular transplantation.","authors":"Hang Zhou, Yu-Xuan Zhang, Quan-Kai Lei, Yu-Mei Li, Yun-Wen Zheng","doi":"10.1186/s13287-025-04447-7","DOIUrl":"10.1186/s13287-025-04447-7","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"338"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544927","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 vesicle-derived lncRNA VIM-AS1 promotes diabetic wound healing by promoting glycolysis and alleviating cellular senescence.","authors":"Feiyuan Liang, Nanchang Huang, Yu Tian, Yuqi Fang, Chuangming Huang, Boyuan Qiu, Tiantian Lu, Li Zheng, Jianwen Cheng, Bo Zhu, Jinmin Zhao","doi":"10.1186/s13287-025-04451-x","DOIUrl":"10.1186/s13287-025-04451-x","url":null,"abstract":"<p><strong>Aims: </strong>Diabetic wound healing is a significant challenge due to impaired cellular functions, and current therapeutic approaches often prove inadequate. This study aims to explore the role of extracellular vesicles (EVs) derived from human umbilical mesenchymal stem cells (HuMSCs), particularly focusing on their associated long non-coding RNAs (lncRNAs), in promoting diabetic wound repair.</p><p><strong>Methods: </strong>To investigate this, we employed lncRNA sequencing of EVs, created reprogrammed EVs, and utilized a diabetic rat  model. The impact of HuMSCs-derived EVs on fibroblast glycolysis, proliferation, and migration was assessed, along with the function of lncRNA VIM-AS1 in glucose metabolism via the PPAR-γ pathway.</p><p><strong>Results: </strong>Our results demonstrate that HuMSCs-derived EVs enhance glycolysis in fibroblasts, which is essential for effective wound healing. We identified lncRNA VIM-AS1 as a pivotal regulator that not only promotes fibroblast proliferation and migration but also significantly enhances endothelial cell function, specifically regarding angiogenesis and tissue vascularization. Furthermore, EVs-derived lncRNA VIM-AS1 was found to reduce reactive oxygen species (ROS) levels, thereby mitigating oxidative stress and cellular senescence in both fibroblasts and endothelial cells. In vivo experiments in rat models confirmed the capacity of EVs-derived lncRNA VIM-AS1 to improve diabetic wound healing.</p><p><strong>Conclusions: </strong>This study highlights the therapeutic potential of HuMSCs-derived EVs and specifically lncRNA VIM-AS1 as innovative approaches to address the challenges of tissue repair in diabetic conditions, offering promising strategies for enhancing wound healing efficacy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"341"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544932","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":"Mechanical force-induced oncostatin M secretion by Jun-positive neutrophils promotes craniofacial bone regeneration for midface hypoplasia treatment.","authors":"Zhixuan Sun, Yujie Chen, Pengbing Ding, Zheng Wang, Zhiyu Lin, Binyi Zhou, Fengyi Hu, Enhang Lu, Haibo Xiang, Xin Yang, Peiyang Zhang, Zhenmin Zhao","doi":"10.1186/s13287-025-04458-4","DOIUrl":"10.1186/s13287-025-04458-4","url":null,"abstract":"<p><strong>Background: </strong>Midfacial hypoplasia is a common craniofacial deformity. Trans-sutural distraction osteogenesis (TSDO), which applies mechanical force to stimulate bone formation at the zygomaticomaxillary sutures (ZMS), has emerged as an effective therapeutic strategy. However, the underlying mechanisms of TSDO-induced osteogenesis remain unclear, resulting in prolonged treatment durations and limited clinical application.</p><p><strong>Methods: </strong>A TSDO model was established in 4-week-old C57BL/6 mice and neutrophil-depleted mice to investigate the role of neutrophils in bone regeneration at the ZMS. Single-cell RNA sequencing was used to characterize neutrophil dynamics and heterogeneity during TSDO, and intercellular signaling pathways were identified through CellChat analysis. Additionally, in vitro stretching experiments using differentiated HL-60 cells were performed to assess the mechanosensitive behavior of neutrophils.</p><p><strong>Results: </strong>In the TSDO model, mechanical distraction significantly increased neutrophil infiltration in the ZMS and surrounding bone marrow. Neutrophil depletion impaired distraction-induced bone formation. Single-cell sequencing revealed that the Jun⁺ neutrophil subset (Jun-Neu) facilitated the osteogenic differentiation of suture-derived stem cells (SuSCs) via secretion of oncostatin M (OSM). In vitro, mechanical stretching (10%, 0.5 Hz) activated the phosphoinositide 3-kinase (PI3K)-AKT pathway in neutrophils, enhancing OSM release and promoting the osteogenic differentiation of SuSCs.</p><p><strong>Conclusions: </strong>This study identifies a mechanical force-neutrophil-bone regeneration axis in TSDO, highlighting the critical role of Jun-Neu-derived OSM in promoting osteogenesis. These findings provide theoretical insights for optimizing TSDO-based clinical strategies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"330"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544935","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":"Prominin-2/FBXO22/BACH1 axis protects bone marrow mesenchymal stem cells against TBHP-induced ferroptosis and ameliorates intervertebral disc degeneration.","authors":"Yuzhu Xu, Lele Zhang, Mingliang Ji, Jun Lu","doi":"10.1186/s13287-025-04453-9","DOIUrl":"10.1186/s13287-025-04453-9","url":null,"abstract":"<p><strong>Background: </strong>Our preliminary research has revealed that Prominin-2 overexpression effectively guarded against oxidative stress (OS)-induced ferroptosis by decreasing BTB and CNC homolog 1 (BACH1) expression, thus promoting bone marrow mesenchymal stem cells (BMSCs) survival under the OS microenvironments in degenerative discs.</p><p><strong>Methods: </strong>In this study, we probed how Prominin-2 controls the BACH1 expression in OS-induced BMSC ferroptosis. We then evaluated the efficiency of targeted Prominin-2/BACH1 pathway in BMSCs in treating degenerative nucleus pulposus cells (NPCs) and intervertebral disc degeneration (IVDD).</p><p><strong>Results: </strong>Using lentivirus infection and Western Blot, we observed that F-box only protein 22 (FBXO22) levels decreased in OS-induced BMSCs while overexpressing Prominin-2 restored its expression and pharmacological inhibition of FBXO22 impaired Prominin-2-mediated BACH1 degradation. The pull-down assay further confirmed the essential role of FBXO22 in the degradation of BACH1 promoted by Prominin-2. FBXO22 overexpression suppressed BMSCs' ferroptosis, and FBXO22 activity enhancer TBE56 (biotinylated TBE31) could further improve Prominin-2-overexpressed BMSCs' viability under OS circumstances. Finally, in vitro co-culture and in vivo studies illustrated that engraftment of Prominin-2-overexpressed BMSCs pre-treated by TBE56 enhanced the treatment efficiency of BMSCs for degenerative NPCs and rats' IVDD.</p><p><strong>Conclusions: </strong>Our data proposed a novel treatment strategy targeting the ferroptosis of BMSCs for treating IVDD by regulating FBXO22 in Prominin-2-overexpressed BMSCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"340"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544941","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":"Pharmacological modulation of stem cells signaling pathway for therapeutic applications.","authors":"Sulaiman Mohammed Alnasser, Abdulrahman Saleh Alrobian, Mohammad Salem Alfayez, Omar Tuwayli Almutairi, Saud Saeed Almutairi, Talal Sami Alkeraidees","doi":"10.1186/s13287-025-04438-8","DOIUrl":"10.1186/s13287-025-04438-8","url":null,"abstract":"<p><p>Stem cells have an exceptional capacity for self-renewal and differentiation and are at the forefront of therapeutics, offering promising solutions for repairing tissues, cancer treatment and the cure of degenerative diseases. Stem cell fate is tightly regulated by key signaling pathways like Hedgehog, TGF-β, Wnt, Hippo, FGF, BMP and Notch, making these pathways prime targets for precision interventions. Despite significant advancements, challenges such as immune rejection, tumorigenesis, and inefficient tissue integration continue to limit clinical success. Pharmacological strategies are emerging as powerful tools to overcome these barriers by enhancing stem cell survival, directing differentiation, and modulating the stem cell niche. Small molecules can activate endogenous stem cells, reducing the need for transplantation while promoting in situ regeneration. Additionally, advancements in gene-editing technologies and biomaterials are further refining stem cell-based therapies. This paves the way for safer, more effective, and personalized therapies. Nevertheless, transforming these innovations into clinical practice entails overcoming regulatory hurdles, optimizing delivery methods, and ensuring long-term safety and efficacy. A multidisciplinary approach integrating personalized medicine, pharmacological modulation, and tissue engineering holds the key to addressing these limitations. Advancing research and refining previous strategies utilizing stem cell therapies has the prospective to revolutionize regenerative and onco-medicine, providing more targeted and sustainable treatment options for a wide range of diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"327"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544940","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 apoptotic vesicles regulate irritable bowel syndrome in mice via the 5-HT brain-gut axis.","authors":"Ya Sun, Di Wu, Lu Lu, Jinyang Wang, Xuanyi Li, Xueli Mao, Yijun Zhang","doi":"10.1186/s13287-025-04448-6","DOIUrl":"10.1186/s13287-025-04448-6","url":null,"abstract":"<p><strong>Background: </strong>Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal disorder characterized by abnormal brain-gut interactions. The pathogenic mechanisms of IBS are not fully understood, and current treatments are limited in efficacy.</p><p><strong>Aims: </strong>This study aims to investigate the potential therapeutic effects of mesenchymal stem cell-derived apoptotic vesicles (apoVs) on IBS in a mouse model, focusing on their impact on the 5-HT brain-gut axis.</p><p><strong>Methods: </strong>We extracted and characterized apoVs from adipose-derived stem cells (ADSCs, Mesenchymal stem cells derived from adipose) induced to undergo apoptosis. IBS was induced in C57BL/6 mice using a chronic stress model. Mice were treated with apoVs via tail vein injection, and various behavioral, physiological, and biochemical parameters were assessed.</p><p><strong>Results: </strong>IBS patients exhibited increased circulating vesicles in peripheral blood, correlating with brain functional activity. Further animal studies found that apoVs treatment in IBS mice reduced 5-HT levels in the brain and gut, alleviated symptoms such as slowed weight gain and visceral hypersensitivity, and restored intestinal barrier function. Additionally, apoVs improved neuronal activation and mucin secretion in the gut.</p><p><strong>Conclusions: </strong>Our findings suggest that apoVs act as novel messengers in brain-gut axis interactions, regulating brain-gut homeostasis. This study provides a new therapeutic approach for the treatment of functional gastrointestinal disorders like IBS.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"326"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544936","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}