Stem Cell Research & Therapy最新文献

{"title":"Endothelial progenitor cell susceptibility to DNA damaging and DDR-modulating compounds determines endothelial differentiation accuracy.","authors":"Sina Federmann, Michelle Westerhoff, Andreas S Reichert, Gerhard Fritz","doi":"10.1186/s13287-026-05087-1","DOIUrl":"10.1186/s13287-026-05087-1","url":null,"abstract":"<p><p>The clinical use of the anticancer drug doxorubicin (Dox) is limited by irreversible cardiotoxicity. The pathophysiological relevance of different cardiac cell types, including endothelial progenitor cells (EPC), in this process is unclear. Since progenitor cells are particularly relevant for tissue regeneration, we hypothesize that residual damage resulting from Dox-based therapeutic regimen may influence their endothelial differentiation accuracy. Therefore, we comparatively investigated the response of murine embryonic stem cells (mESC), endothelial progenitor cells (EC d4) and terminally differentiated endothelial-like cells (EC d6) following exposure to Dox and selected pharmacological inhibitors of DNA repair/DNA damage response (DDR) (RAD51i B02; HDACi entinostat (EST)). We show that EC d4 exhibit enhanced Dox sensitivity as compared to mESC and EC d6. EdU incorporation and replication fork progression analyses revealed pronounced agent-specific differences between mESC, EC d4 and EC d6. Furthermore, DNA damage formation varied in a drug-dependent manner, with mESC showing enhanced residual levels of DNA single-strand breaks (SSB) as compared to EC d4 and EC d6 while EC d6 revealed highest levels of DNA double-strand breaks (DSB). Dox treatment of EC d4 did not prevent their further differentiation into EC d6. However, it caused several functional impairments in the surviving EC d6 progeny, including defects in mitochondrial homeostasis, endothelial barrier function related to cell-cell adhesion factors (ZO1, VE-cadherin), cytokine response and low-density lipoprotein (LDL) uptake. This is accompanied by increased senescence. Summarizing, we demonstrate both overlapping and agent-specific responses of mESC, EC d4 and EC d6 to Dox and DNA repair/DDR inhibitors. Notably, drug treatment of EPC (EC d4) causes multiple dysfunctions in differentiated EC d6. Hence, pharmacological measures aiming to specifically protect EPC from Dox-induced damage are suggested to foster the maintenance of healthy endothelial functionality during regeneration, thereby lowering the risk of detrimental late cardiotoxicity resulting from Dox-based anticancer regimen.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13308190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333354","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":"3D printed nano-hydroxyapatite scaffold combined with BMSCs cell sheet containing concentrated growth factor (CGF) for enhancing bone regeneration.","authors":"Qi Shao, Jianhong Shi, Jin Lu, Yuanye Tian","doi":"10.1186/s13287-026-05076-4","DOIUrl":"10.1186/s13287-026-05076-4","url":null,"abstract":"<p><strong>Background: </strong>Craniofacial bone defects represent significant clinical challenges resulting from diverse etiological factors. Despite advancements in biomaterials science, autologous tissue transplantation remains the gold standard for craniofacial reconstruction due to the limitations of existing materials in replicating the complexity and functionality of native tissues.</p><p><strong>Objective: </strong>This study aimed to investigate the efficacy of combining 3D-printed nano-hydroxyapatite (n-HA) scaffolds with concentrated growth factor-enriched cell sheets (CGF-BMSCs-CS) for bone defect repair, exploring their synergistic effects on osteogenesis and tissue regeneration.</p><p><strong>Methods: </strong>Bone marrow mesenchymal stem cells (BMSCs) were utilized to fabricate CGF-enriched cell sheets. 3D-printed porous n-HA scaffolds (5 mm diameter, 1 mm thickness) were prepared and wrapped with CGF-BMSCs-CS to form composite scaffolds. Four experimental groups were established: control, n-HA alone, CGF-BMSCs-CS alone, and the composite n-HA/CGF-BMSCs-CS. Osteogenic potential was evaluated through alkaline phosphatase (ALP) activity assays and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis of osteogenesis-related gene expression. Sprague-Dawley rats were randomly assigned to these groups for a cranial defect model. Micro-computed tomography (µCT) was performed at 6 and 12 weeks post-surgery to assess bone regeneration metrics, including bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th).</p><p><strong>Results: </strong>Scanning electron microscopy (SEM) confirmed the n-HA scaffold's uniform porosity and structural integrity. The CGF-BMSCs-CS exhibited optimal thickness and viscosity for tissue engineering applications. The composite group demonstrated significantly elevated ALP activity and upregulated expression of osteogenesis-related genes, indicating enhanced osteogenic capacity. µCT analysis revealed superior bone formation and osseointegration in the composite scaffold group compared to other groups. This was further supported by significantly higher bone mineral density (BMD) values at both time points (p < 0.05). Histological evaluation via hematoxylin and eosin (H&E) staining showed increased osteocyte activity, neovascularization, and trabecular bone formation in the composite group.</p><p><strong>Conclusions: </strong>We innovatively integrated 3D printed n-HA scaffolds with CGF BMSCs CS, which combines mechanical stability with enhanced osteogenic potential for craniofacial bone defect repair, promoting bone healing. This innovative strategy provides promising prospects for advancing bone tissue engineering and regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333186","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":"Mapping the evolutionary landscape of intestinal organoids: from self-organization biology to precision medicine.","authors":"Fengni Liang, Zerong Pei, Xuemei Wang, Ke Zhang","doi":"10.1186/s13287-026-05094-2","DOIUrl":"10.1186/s13287-026-05094-2","url":null,"abstract":"<p><p>The advent of intestinal organoids has fundamentally transformed biomedical research by providing a physiological ex vivo model that recapitulates native tissue architecture. Despite an exponential surge in publications, a comprehensive mapping of the field's evolutionary trajectory remains lacking. This study employs bibliometric analysis to dissect the global landscape of intestinal organoid research from 1986 to 2025, utilizing data from the Web of Science Core Collection. By leveraging VOSviewer and bibliometrix tools, we demonstrate that while the USA dominates in publication quantity, the Netherlands commands the highest citation influence, reflecting the enduring legacy of foundational works by Sato and Clevers. Co-citation and keyword trend analyses demonstrate evolving research priorities. The field initially focused on stem cell differentiation and culture optimization, then expanded into disease modeling of colorectal cancer and inflammatory bowel disease. Notably, recent burst detection identifies a clear pivot towards \"organ-on-a-chip\" technology, \"mechanobiology,\" and \"single-cell sequencing\". These hotspots signal the advent of precision engineering. Bioengineering and high-throughput omics together drive the development of next-generation physiologically relevant intestinal models. Ideally, this bibliometric blueprint serves as a navigational guide for researchers, highlighting the paradigm shift towards complex, engineered micro-physiological systems (MPS) as the future of intestinal research.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318987","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":"iRGD-modified 3D exosomes delivered miR-99b-5p induces ferroptosis to inhibit colorectal cancer progression by regulating FGFR3/PI3K/AKt pathway.","authors":"Xiao-Huan Li, Fu-Wei Lian, Feng Lv, Xiao-Ling Luo, Bang-Li Hu, Li-Tu Zhang, Shu-Fang Ning","doi":"10.1186/s13287-026-05129-8","DOIUrl":"10.1186/s13287-026-05129-8","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs)-derived exosomes present great potential as nanocarriers for targeted drug delivery. Moreover, the therapeutic efficacy of exosomes can be substantially enhanced through functional modifications and the incorporation of bioactive molecules.</p><p><strong>Methods: </strong>In this study, the MSCs were cultured under two-dimensional (2D) and three-dimensional (3D) cell culture conditions. The culture supernatants were collected for isolating exosomes. The characteristics and yields of exosomes from 2D and 3D cultures were detected by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), western blot analysis, and bicinchoninic acid (BCA) assay. Subsequently, 3D exosomes were loaded with miR-99b-5p and modified with iRGD peptide were formed into a new engineered exosome, designated as iRGD-Exo-miR-99b-5p. The effects of these engineered exosomes on the progression of colorectal cancer (CRC) were assessed through a series of in vivo and in vitro experiments.</p><p><strong>Results: </strong>The 3D-cultured MSCs exhibited a higher yield of exosomes and enhanced uptake by CRC cells. Further in vitro experiments demonstrated that 3D-exosomes loaded with miR-99b-5p effectively inhibit the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells. Results from a xenograft tumor model indicate that iRGD-modified exosomes were significantly enriched at tumor sites. Furthermore, exosomes modified with iRGD and loaded with miR-99b-5p were employed for CRC treatment, resulting in substantial tumor growth inhibition and enhanced the chemotherapy efficacy of 5-fluorouracil (5-FU) in vivo, without inducing notable toxicity or side effects. Mechanistically, exosome-mediated delivery of miR-99b-5p downregulated FGFR3 expression, thereby inhibiting the activation of the PI3K/AKt signaling pathway and promoting ferroptosis, ultimately attenuating CRC progression.</p><p><strong>Conclusions: </strong>Collectively, iRGD-modified 3D exosomes loaded with miR-99b-5p were able to specifically target tumor sites, thereby significantly suppressing CRC growth through the induction of ferroptosis via regulating the FGFR3/PI3K/AKt signaling pathway. These findings suggest that functional engineering and bioactive loading of 3D-exosomes derived from MSCs represent a promising strategy for targeted cancer therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309515","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":"SIRT6 enhances the therapeutic potential of extracellular vesicles in mitigating osteoarthritis in rat models.","authors":"Guihua Yang, Su Liu, Huitian Han, Xueyan Yang, Feng Li, Qiong Wu, Zhiyu Zhao, Fei Liu, Zhifa Zheng, Guangxi Gao, Wenjing Ma, Lina Zhao, Baohua Liu, Zhihong Wu","doi":"10.1186/s13287-026-05112-3","DOIUrl":"10.1186/s13287-026-05112-3","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapeutic candidates for osteoarthritis (OA). Sirtuin 6 (SIRT6), a class III histone deacetylase, exerts protective effects by preventing cellular senescence, reducing inflammation, and promoting longevity. This study aims to generate immortalized hUCMSCs with SIRT6 and telomerase reverse transcriptase (TERT) overexpression and investigate the therapeutic potential of their secreted EVs (EVs@SIRT6) in OA.</p><p><strong>Methods: </strong>hUCMSCs were genetically engineered using lentiviral transduction to overexpress SIRT6 and TERT, referred to as SIRT6/TERT-hUCMSCs. Natural EVs and EVs@SIRT6 were isolated via differential ultracentrifugation and characterized by morphology, size distribution, marker expression, and proteomic signature. Their effects on IL-1β stimulated chondrocytes were assessed in vitro, including cell viability, apoptosis, scratch closure, inflammatory cytokine secretion, and oxidative stress. Transcriptomic alterations were analyzed by RNA sequencing. Therapeutic efficacy in vivo was evaluated in a rat anterior cruciate ligament transection (ACLT) model via micro-computed tomography, histological analyses, and immunohistochemistry.</p><p><strong>Results: </strong>SIRT6/TERT-hUCMSCs preserved mesenchymal identity, trilineage differentiation potential, and sustained proliferative capacity up to passage 60, accompanied by longer telomeres and reduced senescence compared to parental cells. EVs@SIRT6 maintained typical EV features but were enriched in SIRT6 protein and displayed a distinct proteomic signature, comprising 1,440 unique proteins associated with nuclear/chromatin repair. In vitro, EVs@SIRT6 more effectively enhanced chondrocyte viability and wound healing while reducing apoptosis compared with natural EVs. EVs@SIRT6 also markedly alleviated inflammatory response, promoted anabolism, suppressed catabolism, and mitigated oxidative stress in chondrocytes. The protective effects of EVs@SIRT6 on chondrocytes were associated with the suppression of the JAK-STAT signaling pathway. Studies in a rat ACLT model further confirmed that EVs@SIRT6 outperformed natural EVs in attenuating subchondral osteosclerosis, reducing osteophyte formation, and mitigating cartilage damage.</p><p><strong>Conclusions: </strong>Engineered EVs@SIRT6 outperform natural EVs in preserving chondrocytes homeostasis and reducing OA progression, establishing an efficient platform for preparing engineered EVs for clinical application.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309488","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":"FDA roadmap to reducing animal testing: a regulatory and scientific paradigm shift in nonclinical safety assessment.","authors":"Yiting Lei, Rocky S Tuan, Zhong Alan Li","doi":"10.1186/s13287-026-05090-6","DOIUrl":"10.1186/s13287-026-05090-6","url":null,"abstract":"<p><p>On April 20, 2026, the U.S. Food and Drug Administration FDA published a 1-year progress report of its initiative to reduce animal testing requirement in drug development. The FDA roadmap, announced on April 10, 2025, represented a pivotal paradigm shift toward human-centric New Approach Methodologies (NAMs), including stem cell-derived organoids, organs-on-chips, in silico modeling, and AI-enabled tools. The aim is to address the longstanding challenges of conventional preclinical safety assessment using animal models, including poor translational predictability, high cost, ethical concerns, and inherent interspecies biological differences, resulting in high clinical attrition and delayed access to effective therapies. In this commentary, we critically evaluate the scientific rationale, first-year implementation progress, and global regulatory impact of the FDA initiative. We highlight landmark advances including the permanent Innovative Science and Technology Approaches for New Drugs (ISTAND) program, human-centric validation principles, streamlined nonclinical frameworks for biologics, and alignment with global agencies and regulators. We also discuss existing, persistent challenges, such as uneven validation across toxicological endpoints, incomplete global data sharing, and cultural inertia, and propose actionable strategies to accelerate the safe, systematic adoption of NAMs in regenerative medicine and drug development.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296033","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":"Stem cell-based tactics in the remodeling and treatment of intestinal diseases.","authors":"Yanian Ren, Shanshan Zhang, Jiageng Wang, Yuanxin Wang, Mingyi Xu, Lei Zhang, Keli Ge, Yongli Chu, Leisheng Zhang","doi":"10.1186/s13287-026-05124-z","DOIUrl":"10.1186/s13287-026-05124-z","url":null,"abstract":"<p><p>Intestinal diseases are imposing a prevalent socioeconomic burden worldwide, which is largely attributed to the disrupted homeostasis of gut-immune crosstalk including gut microbiota dysbiosis and immunomodulatory imbalance. Stem cells are unique cell populations with self-renewal and multi-lineage differentiation properties, and current literature has indicated the remarkable applications in early embryogenesis, disease remodeling and novel cytotherapy via diverse modes of action (e.g., direct- or trans-differentiation, cytokine paracrine, and bidirectional immunomodulation). Of them, human pluripotent stem cells (hPSCs) and the derivatives, including the self-organizing organoids, have been vastly employed for intestinal disease remodeling, while mesenchymal stem/stromal cells (MSCs) and the microvesicles are adopted for multifarious intestinal disorder intervention. In this review article, we mainly focus on the progressions in stem cell-based disease remodeling (intestinal lineage and organoid induction from hPSCs) and cellular therapy for intestinal diseases (e.g., inflammatory bowel disease, infectious intestinal diseases, and colorectal cancer), together with the underlying repair mechanisms (e.g., target genes and signaling pathways). Furthermore, the promising prospective and the concomitant challenges of stem cell-based preclinical and clinical investigations upon intestinal disorders are also outlined, including ethical considerations and supervision, heterogeneity and standardization, integration with novel biotechnologies (e.g., single-cell RNA sequencing, intracellular tracing, gene-editing and three-dimensional bioprinting). Collectively, our findings will supply profitable references and facilitate the development of stem cell-based mechanistic investigation and regenerative medicine for intestinal diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303121","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":"Potential role of natural products in veterinary stem cell therapy.","authors":"Asiyeh Shojaee","doi":"10.1186/s13287-026-05117-y","DOIUrl":"10.1186/s13287-026-05117-y","url":null,"abstract":"<p><p>In veterinary medicine, stem cells therapy is mostly used to treatment of orthopedic condition. Stem cell behavior is shaped by numerous intrinsic and extrinsic factors. Traditional medicinal herbs-long used to prevent and treat diverse diseases-together with other natural bioactive compounds have attracted increasing interest because of their potential to modulate stem cell function. Many of these agents exhibit antioxidant, anti-inflammatory, anticancer, and anti-apoptotic activities and may support tissue regeneration by enhancing proliferation, differentiation, and migration. Importantly, natural products may offer safer and more cost-effective alternatives to synthetic growth factors in regenerative strategies. Accordingly, this review summarizes recent evidence on medicinal plants, phytochemicals, algal extracts, and related bioactive compounds that influence veterinary stem cells, and discusses their potential applications in regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296422","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":"Bone marrow mesenchymal stem cell-derived TSG-6 regulates microglial pyroptosis and alleviates bone cancer pain by inhibiting the NLRP3 inflammasome.","authors":"Danyang Xu, Mengna Jiang, Hao Ming, Jing Zhang, Yunqi Li, Ping Wu, Qingping Wen","doi":"10.1186/s13287-026-05121-2","DOIUrl":"10.1186/s13287-026-05121-2","url":null,"abstract":"<p><strong>Background: </strong>The central sensitization mechanism of bone cancer pain is related to neuroinflammation, glial cell activation, and an acidic environment. Among them, the NLRP3 inflammasome is involved in the occurrence of bone cancer pain. Studies have shown that an intrathecal injection of bone marrow mesenchymal stem cells (BMSCs) alleviates bone cancer pain by inhibiting microglial cell activation. Upon inflammatory stimulation, BMSCs produce increased levels of Tumor necrosis factor-α-stimulated gene 6 (TSG-6), which regulates intercellular signaling and inflammatory responses; however, whether the secretion of TSG-6 from BMSCs inhibits NLRP3-mediated microglial pyroptosis to alleviate bone cancer pain is unknown. Therefore, this study aimed to evaluate the analgesic effect of TSG-6 released by BMSCs on bone cancer pain (BCP) and explore its potential mechanisms through in vitro and in vivo experiments.</p><p><strong>Methods: </strong>In vivo, Walker 256 breast cancer cells were injected into the bone marrow cavity of the left tibia of rats to establish a BCP model. On days 7 and 14 after surgery, intrathecal injections of BMSCs or exogenous recombinant TSG-6 were administered, and the analgesic effects were observed at 2, 4, 8, 24, and 48 h after administration. Spinal cord tissues were collected for Western blotting and immunofluorescence staining to assess the activation of the NLRP3 signaling pathway. In vitro, BV2 microglia were cocultured with BMSCs or recombinant TSG-6, and the same detection methods were performed to evaluate changes in the levels of proteins involved in the NLRP3 signaling pathway. BMSCs transfected with TSG-6-targeting shRNA were intrathecally injected in vivo or cocultured with microglia in vitro to investigate whether TSG-6 is involved in the inhibition of microglial pyroptosis and the inflammatory response mediated by BMSCs to alleviate BCP.</p><p><strong>Results: </strong>BMSC transplantation or treatment with exogenous recombinant TSG-6 significantly improved BCP-related behaviors, inhibited the expression of key proteins in the NLRP3 signaling pathway in spinal dorsal horn microglia in rats, and reduced the release of inflammatory factors. Experiments revealed that coculturing BMSCs with BV2 microglia or treating BV2 cells with exogenous recombinant TSG-6 inhibited the LPS-induced activation of NLRP3 in BV2 cells and regulated microglial pyroptosis. Transfection of BMSCs with TSG-6-targeting shRNA significantly weakened the inhibitory effect on microglial pyroptosis.</p><p><strong>Conclusion: </strong>In vivo and in vitro experiments revealed that bone marrow mesenchymal stem cells inhibit the NLRP3 signaling pathway to regulate the pyroptosis of microglia through the secretion of TSG-6, thereby alleviating bone cancer pain.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296397","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":"Amnion-derived mesenchymal stem cells attenuate anti-GBM glomerulonephritis via regulation of neutrophil CD44 expression.","authors":"Tomoya Nozaki, Kumiko Fujieda, Kazuhiro Furuhashi, Yuko Shimamura, Munetoshi Karasawa, Eri Koshi-Ito, Yu Watanabe, Chikao Onogi, Keita Hattori, Akihisa Kato, Jun Matsumoto, Tomohiro Kawazoe, Asuka Horinouchi, Akihito Tanaka, Hangsoo Kim, Kayaho Maeda, Makoto Matsuyama, Kenichi Yamahara, Shoichi Maruyama","doi":"10.1186/s13287-026-05113-2","DOIUrl":"10.1186/s13287-026-05113-2","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) possess immunomodulatory and tissue repair properties, and their therapeutic efficacy has been reported in models of glomerulonephritis. However, the clinical application of bone marrow-derived MSCs (BMSCs) is limited due to the invasive nature of bone marrow harvesting. In this study, we focused on amnion-derived MSCs (AMSCs), which can be obtained non-invasively after delivery, and investigated their therapeutic effects in a rat model of anti-glomerular basement membrane (GBM) nephritis.</p><p><strong>Methods: </strong>In a rat model of anti-GBM nephritis, human AMSCs, BMSCs, or vehicle were intravenously administered. Evaluations included renal function, histology, intravital imaging of glomerular neutrophils, and flow cytometric analysis of leukocytes. In addition, we used an anti-CD44 neutralizing antibody in vivo to examine the therapeutic relevance of CD44 blockade, including its impact on neutrophil.</p><p><strong>Results: </strong>The renoprotective effects observed in the AMSC-treated group were comparable to or greater than those in the BMSC-treated group. Furthermore, neutrophils exposed to AMSCs exhibited shorter dwell time in the glomeruli, and specifically in renal neutrophils, the expression of the adhesion molecule CD44 was reduced. In addition, administration of an anti-CD44 antibody produced similar renoprotective effects and reductions in neutrophil infiltration, suggesting that modulation of CD44 signaling contributes to the renoprotective effects of AMSCs.</p><p><strong>Conclusions: </strong>Collectively, these findings indicate that AMSCs exert renoprotective effects comparable to or greater than those of BMSCs, and may represent a novel therapeutic approach for anti-GBM nephritis by specifically suppressing CD44 expression in neutrophils at sites of inflammation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284535","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}