Stem Cell Research & Therapy最新文献

{"title":"Psoralen enhances direct cardiac reprogramming via activating PPARα and driving mitochondrial fission and improves cardiac function after myocardial infarction.","authors":"Wenjie Li, Haixia Liu, Xinyu Wan, Ding Cheng, Zhiguo Zhang, Ruyuan Zhu","doi":"10.1186/s13287-026-05160-9","DOIUrl":"10.1186/s13287-026-05160-9","url":null,"abstract":"<p><strong>Background: </strong>Direct cardiac reprogramming offers a promising strategy to regenerate cardiomyocytes for heart repair, but its efficiency and maturation remain limited. Psoralen, a natural compound isolated from Psoralea corylifolia L., has been widely studied for its bioactive properties. This study aimed to determine whether psoralen enhances chemical cardiac reprogramming and improves functional maturation, and to evaluate its therapeutic potential in myocardial infarction.</p><p><strong>Methods: </strong>Mouse embryonic fibroblasts were treated with a chemical reprogramming cocktail containing RepSox and Forskolin, with or without psoralen. Gene expression was assessed by quantitative PCR and Western blotting. Sarcomere ultrastructure was examined by transmission electron microscopy. Mitochondrial content and morphology were analyzed using MitoTracker staining. Calcium handling was evaluated in Fluo-4 loaded induced cardiomyocytes. Metabolic profiles were measured with Seahorse assays. RNA sequencing and protein-protein interaction analysis were used to identify signaling pathways activated by psoralen. To investigate the functional role of mitochondrial fission in psoralen enhanced reprogramming, the DRP1 inhibitor Mdivi-1 was added to the reprogramming cocktail. An immortalized human skin fibroblast cell line was additionally used to evaluate cardiac marker expression and mitochondrial morphology following treatment with RepSox, Forskolin, and psoralen. For in vivo evaluation, a myocardial infarction model was generated in male C57BL/6J mice, which were subsequently treated for 7 days. Cardiac function was measured by echocardiography, and histological changes were assessed by HE and Masson's trichrome staining.</p><p><strong>Results: </strong>Psoralen (10 µM) significantly increased the induction efficiency of induced cardiomyocytes, leading to the rapid appearance of beating clusters(day 1 vs. day 6-8) and marked upregulation of cardiac structural genes. Psoralen-treated cells displayed enhanced sarcomere organization, improved calcium transients, and a metabolic shift toward oxidative phosphorylation characterized by higher mitochondrial respiration and reduced glycolysis. Transcriptomic profiling identified activation of the PPAR signaling pathway, with PPARα, RXRG, and UCP1 as central nodes. Psoralen also enhanced mitochondrial fission by upregulating fission-related genes and proteins. Mdivi-1 attenuated psoralen-induced cardiac gene expression and mitochondrial fragmentation. In immortalized human skin fibroblasts, psoralen combined with RepSox and Forskolin increased cardiac marker expression and promoted mitochondrial fragmentation. In vivo, psoralen combined with RepSox and Forskolin enhanced cardiac function and reduced fibrosis after myocardial infarction compared to RepSox and Forskolin alone.</p><p><strong>Conclusion: </strong>Psoralen enhances chemical direct cardiac reprogramming by activating metabolic and ","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412874","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":"Safety evaluation of repeated administration of umbilical cord mesenchymal stem cell-derived exosomes.","authors":"Ting Lan, Tao-Tao Tang, Jing-Jing Di, Suo-Fu Qin, Aihemaiti Muzaipaier, Qin-Yu Zhou, Bi-Cheng Liu, Qiu-Li Wu","doi":"10.1186/s13287-026-05172-5","DOIUrl":"10.1186/s13287-026-05172-5","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cell-derived exosomes (MSC-Exos) have shown considerable therapeutic potential in regenerative medicine. However, the biosafety profile of these exosomes following repeated administration has not been adequately characterised, and this knowledge gap continues to hinder clinical translation.</p><p><strong>Methods: </strong>Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) were produced on a xeno-free platform by replacing fetal bovine serum (FBS) with human platelet lysate (hPL). A relatively comprehensive and integrated repeated-dose preclinical biosafety profile assessment was then conducted using polyethylene glycol (PEG)-Liposomes as reference nanovesicles. The assessment included pharmacokinetic and distribution analyses using DiD labelling, haematological cytology testing, quantitative measurement of inflammatory cytokines and chemokines, histopathological scoring, and RNA sequencing.</p><p><strong>Results: </strong>In this study, the safety assessment revealed that: (1) hucMSC-Exos primarily accumulated in the liver and spleen and exhibited an approximately 4-h circulation time; (2) repeated intravenous administration of hucMSC-Exos for 30 days did not result in overt systemic inflammation, and the evaluated haematological and biochemical parameters remained within the normal range; (3) RNA sequencing showed that hucMSC-Exos avoided immune pathway activation (e.g., IL-17/antigen presentation) triggered by PEG-Liposomes, instead enriching complement-coagulation cascades (e.g., C1qc, C6 upregulation) and metabolic pathways (steroidogenesis, retinol metabolism). Together, these findings suggest that hucMSC-Exos have a favourable biosafety profile in a murine model and support further preclinical evaluation for regenerative medicine applications.</p><p><strong>Conclusion: </strong>This study suggests that repeated intravenous administration of hucMSC-Exos confers a relatively favourable biosafety profile in a murine model and provides preliminary preclinical evidence for further investigation towards clinical translation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412215","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":"LGR5 as a therapeutic target for decidualization-based endometrial mesenchymal stem cells therapy in thin endometrium.","authors":"Kai Chen, Xueqing Ning, Huiru Wang, Jingxin Wang, Xin Zhao, Lu Zong, Shengxia Zheng","doi":"10.1186/s13287-026-05173-4","DOIUrl":"10.1186/s13287-026-05173-4","url":null,"abstract":"<p><strong>Background: </strong>Decidualization of endometrial mesenchymal stem cells (ESCs) is crucial for the implantation of the embryo. Thin endometrium (TE) can impair endometrial receptivity by affecting the decidualization of ESCs. However, how TE affects the decidualization of ESCs remains unclear.</p><p><strong>Methods: </strong>Through multiple transcriptome analyses, we found that LGR5 plays a crucial role in the decidualization of ESCs. In vitro, siRNA was used to knock down LGR5 in ESCs, and decidualization was assessed via morphology, qRT-PCR, Western blot, and ELISA for decidualization marker (PRL, IGFBP-1). Colony forming assay, EdU, CFSE, and tube formation were used to evaluate proliferation and secretion. Signaling pathway components (β-catenin, AXIN2, PGR) were analyzed. In vivo, an adeno-associated virus (AAV) delivered shRNA to knock down Lgr5 in mouse uterine to assess endometrial receptivity and pregnancy rates. A TE mouse model was established and treated with decidualized endometrial mesenchymal stem cells (DSCs) or LGR5-knockdown DSCs to evaluate therapeutic efficacy.</p><p><strong>Results: </strong>LGR5 was significantly upregulated during decidualization and downregulated in TE tissues. In vitro, LGR5 knockdown impaired DSCs' morphological transformation, reduced decidualization, restored proliferation, but diminished secretory function and angiogenic potential. Mechanistically, LGR5 knockdown suppressed the β-catenin pathway and downregulated progesterone receptor (PGR). In vivo, Lgr5 knockdown reduced endometrial thickness, receptivity markers (Lif, Hoxa10, Pgr), and embryo implantation numbers. Crucially, transplanting LGR5-knockdown DSCs into TE mice resulted in inferior restoration of endometrial structure, reduced angiogenesis, and lower pregnancy rates compared to DSCs.</p><p><strong>Conclusion: </strong>LGR5 plays an important role in ESCs decidualization and may contribute to the therapeutic efficacy of DSCs for TE repair, potentially through regulation of PGR via the β-catenin pathway. These results indicate that LGR5 represents a candidate target worthy of further investigation for developing function-restoring therapies in TE.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412899","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":"Evaluation of the hydrogels Matrigel, Biogelx, PLTMAx and GelMA in the generation of minilungs from human embryonic stem cells (hESC).","authors":"Irene Chamorro-Herrero, Julio Sempere, José Yuste, Alberto Zambrano","doi":"10.1186/s13287-026-05165-4","DOIUrl":"10.1186/s13287-026-05165-4","url":null,"abstract":"<p><p>Organoids isolated from adult cells and, especially, those synthesized from human pluripotent stem cells, both induced (hiPSCs) or embryonic stem cells, (hESCs), offer unique opportunities for disease modeling, drug testing or organ replacement (regenerative medicine). The biofabrication of functional tissue require supportive biomaterials and scaffolds generated from reliable materials. Due to the murine origin of the market choice hydrogel (Matrigel), its suitability for regenerative medicine or clinical translation is greatly limited. Thus, the development of new supportive materials for long-term cell survival and differentiation of pluripotent stem cells which are biocompatible with clinical translation and automatized synthesis, or bioprinting, is an urgent need. In the present study, we have evaluated the suitability of four representative hydrogels, also fitting as bioinks, as supportive biomaterials for cell growth and differentiation of respiratory organoids or minilungs from hESCs. The hydrogels Biogelx, PLTMax and GelMA, were evaluated in the generation of minilungs in parallel to Matrigel. In contrast to those in Matrigel, the minilungs embedded into the hydrogels tested were smaller, less branched or fragmented. The minilungs showed the expression of three surfactant proteins, despite exhibiting abnormal structures. The aberrant cell growth and cellular arrangement observed suggest that these promising hydrogels or bioinks tested might not be biocompatible for organoid differentiation and for establishing future strategies based on automatized synthesis or bioprinting of lung tissue.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412871","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":"Activation of the G-protein coupled estrogen receptor 1 (GPER1) reduces transient receptor potential vanilloid 1 (TRPV1) activity and human iPSC-derived nociceptive neuron firing.","authors":"Oliver Dräger, Angelique Grell, Asaria E Vogel, Erhard Wischmeyer, Beatrice A Nossek","doi":"10.1186/s13287-026-05174-3","DOIUrl":"10.1186/s13287-026-05174-3","url":null,"abstract":"<p><p>Chronic pain affects approximately one fifth of people worldwide and displays a huge burden for health care institutions. Some chronic pain conditions have a higher prevalence in women than men. Previous studies related these sex-specific differences to sex-hormone receptor activation and interaction with pain-related receptors like the transient receptor potential vanilloid 1 (TRPV1). Here, especially estrogen seems to play a crucial role. While the role of estrogen receptor alpha and beta in modulating TRPV1 has already been studied, the interplay of the membrane-bound and G-protein -coupled estrogen receptor (GPER1) with nociceptor-associated ion channels is still unknown. The study at hand focuses on the establishment of a human induced pluripotent stem cell (iPSC) -based nociceptor model to unravel the effect of GPER1 activation on nociceptor excitability. Therefore, a human dermal fibroblast cell line was successfully reprogrammed into the iPSC line BO-VC1 and subsequently differentiated into nociceptors expressing GPER1 besides TRPV1 and the Twik-related spinal cord potassium channel (TRESK). The activation of GPER1 by its specific agonist G-1 led to significantly reduced action potential firing rates and TRPV1-mediated calcium influx. In addition, GPER1 was found to downregulate TRPV1-mediated ion currents upon G-1 treatment in a human embryonic kidney cell -based model. Our findings support the hypothesis that GPER1 activation silences neuronal excitability in nociceptors, probably being a candidate for future research focusing on targeted pain modulation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405922","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-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway.","authors":"Yalin Han, Xi Xu, Shan Zhao, Hui Wang, Shengmei Wei, Jia Xu, Yina Wang, Yuan Hu, Xinyue Li, Jiamin Ai, Guangping Lang, Yingying Han","doi":"10.1186/s13287-026-05146-7","DOIUrl":"10.1186/s13287-026-05146-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Periodontitis, characterized by chronic inflammation and alveolar bone loss, poses significant challenges to oral health. Interleukin-38 (IL-38) has emerged as a potential therapeutic agent due to its anti-inflammatory properties. This study aimed to investigate whether and how IL-38 protects against periodontitis in a ligation-induced periodontitis (LIP) mouse model and an inflammatory osteogenic model using human periodontal ligament stem cells (hPDLSCs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;40 mice were divided into 4 groups (n = 10/group): Control, LIP, LIP + phosphate-buffered saline (PBS), LIP + IL-38. The animals were euthanized and tissue samples (jaws and gingivae) were collected on day 5. Recombinant mouse IL-38 (rmIL-38) lentivirus was used for IL-38 overexpression or knockdown in hPDLSCs in vitro, and shIL-38 hPDLSCs were ultimately treated with the NF-κB inhibitor Bay11-7082. The above tissue and cellular samples were collected for micro-computed tomography (micro-CT) imaging, histological, polymerase chain reaction (qRT-PCR) and Western blot (WB) to analyze bone microstructure, inflammatory markers, osteogenic markers, and the relevant protein level of the nuclear factor kappa B (NF-κB) pathway. Correction version for Methods: Forty mice were randomized into four groups (n = 10 per group): Control, ligature-induced periodontitis (LIP), LIP + PBS, and LIP + recombinant mouse IL-38 (rmIL-38). The LIP + rmIL-38 group received daily gingival rmIL-38 injection, and all mice were euthanized on day 5 to harvest jaw and gingival tissues. In vitro, lentiviral transfection generated IL-38-overexpressing and IL-38-knockdown hPDLSCs; NF-κB inhibitor Bay11-7082 was applied to IL-38-knockdown hPDLSCs for rescue assays. All tissue and cell samples were analyzed via micro-computed tomography (micro-CT) imaging, histological, polymerase chain reaction (qRT-PCR) and Western blot (WB) to analyze bone microstructure, inflammatory markers, osteogenic markers, and the relevant protein level of the nuclear factor kappa B (NF-κB) pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vivo, rmIL-38 administration significantly reduced pro-inflammatory cytokine expression (Il1b, Il17a, Il6 and Il23a) and suppressed NF-κB pathway activation, which can be evidenced by decreased phospho-p65 levels. Furthermore, micro-CT analysis showed that rmIL-38 mitigated alveolar bone loss and improved the bone microstructure assessed. In vitro, IL-38 overexpression enhanced osteogenic marker expression (ALP, RUNX2, and COL1A1) while inhibiting NF-κB signaling, whereas IL-38 knockdown produced the opposite effects. Notably, Bay11-7082 treatment rescued impaired osteogenic marker expression in IL-38 knockdown hPDLSCs. Correction version for Results: In vivo, local rmIL-38 administration markedly suppressed pro-inflammatory cytokines Il17a and Il23a and upregulated the anti-inflammatory cytokine Il10. Micro-CT, immunofluorescence and Masson staining further co","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405969","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":"Isolation of human satellite cells using CD29/CDH15 and a nanoparticle-based live Pax7 mRNA detection system, and their expansion with extracellular matrix and its derivatives.","authors":"Shudong Zhao, Shubhankar Sood, Ruixiang Yu, Luis Arvizu Gutierrez, Takhmina Ayupova, Sara Taiyari, Jonathan Miles, Stephen Hamilton, Massimiliano Cerletti","doi":"10.1186/s13287-026-05134-x","DOIUrl":"10.1186/s13287-026-05134-x","url":null,"abstract":"<p><p>Human skeletal muscle stem cells, also called satellite cells, have great potential for treating neuromuscular diseases and combating muscle aging. However, progress toward clinical use has been limited by the scarcity of donor tissue and the technical challenges of isolating, preserving, and culturing these rare cells. In this study, we introduce a new combination of cell surface markers and a gold nanoparticle-based live Pax7 mRNA detection system, both of which enable efficient isolation of human satellite cells. Additionally, we show that extracellular matrix (ECM) components support the maintenance of human satellite cells and improve their function in vivo. These findings provide integrated methods to enhance the production of human muscle-forming cells for translational and clinical applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405942","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":"Humoral immune response to equine mesenchymal stem/stromal cells (MSCs): MHC compatibility has more influence than inflammatory priming or chondrogenic differentiation.","authors":"Alina Cequier, Antonio Romero, Elvira Bernad, Belén Serrano, Arantza Vitoria, Sara Fuente, Irene Fernández, Pilar Zaragoza, Francisco José Vázquez, Laura Barrachina, Clementina Rodellar","doi":"10.1186/s13287-026-05157-4","DOIUrl":"10.1186/s13287-026-05157-4","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem/stromal cells (MSCs) hold great potential for treating various conditions, but their effectiveness and safety in allogeneic therapies can be affected by the recipient's immune response, among other factors. Allogeneic MSC administration has been associated with immune recognition in different species, including horses. These animals are both veterinary patients and translational models, offering valuable insights into how allogeneic MSCs interact with the immune system in vivo. Factors such as inflammation, chondrogenic differentiation, and major histocompatibility complex (MHC) compatibility between donor and recipient can influence immune responses, potentially affecting the feasibility of repeated MSC administrations. This study evaluates the humoral immune response following repeated administration of chondrogenically differentiated (MSC-chondro), pro-inflammatory primed (MSC-primed), and basal (MSC-naïve) equine MSCs into autologous, MHC-matched, and MHC-mismatched recipients.</p><p><strong>Methods: </strong>Equine MSC-chondro, MSC-primed or MSC-naïve were embedded into alginate scaffolds and repeatedly implanted subcutaneously into autologous, MHC-matched or MHC-mismatched allogeneic horse recipients. Serum samples collected before and 1, 3, and 6 weeks after each administration were analysed for cytotoxic allo-antibodies against donor MHC. Recipient sera (neat, 1:2 and 1:16 dilution) were tested against donor-derived target cells using two-stage microcytotoxicity assays.</p><p><strong>Results: </strong>Autologous and MHC-matched recipients did not develop antibodies against the MHC of the donor, regardless of the MSC type administered. In contrast, MHC-mismatched horses developed allo-antibodies after the first administration, with a notable increase following the second administration. All the MSC types triggered a humoral immune response in MHC-mismatched recipients, but MSC-chondro provoked the strongest immune recognition.</p><p><strong>Conclusions: </strong>Donor-recipient MHC compatibility was more important than inflammatory priming or chondrogenic differentiation of equine MSCs to prevent the development of allo-antibodies. Thus, when donor and recipient are MHC-matched, different types of equine MSCs (MSC-chondro, MSC-primed or MSC-naïve) could be administered without producing a humoral response.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405926","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":"Role of microRNAs in cisplatin response of cancer stem cells.","authors":"Meysam Moghbeli, Bahareh Payami","doi":"10.1186/s13287-026-05161-8","DOIUrl":"10.1186/s13287-026-05161-8","url":null,"abstract":"<p><p>Cisplatin (CDDP)-based chemotherapy remains a cornerstone of cancer treatment, but its efficacy is often limited by the development of chemo resistance that is mainly associated with cancer stem cells (CSCs). MicroRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators of gene expression, critically influencing key cellular processes, including drug response. This review aims to provide a comprehensive analysis of the current evidence elucidating the role of specific miRNAs in governing the CDDP response of CSCs. We conducted a systematic assessment of all available scientific literature databases up to (Nov 2025) to identify relevant studies. Our analysis reveals that miRNAs function as a dynamic network, either promoting or reducing CDDP resistance in CSCs through regulation of signaling pathways, apoptosis, DNA repair pathways, and ABC drug transporters. We identified several consistently reported oncomiRs (e.g., miR-21, miR-765, and miR-132) that were up regulated in CSCs and confer CDDP resistance. Conversely, tumor-suppressor miRNAs were frequently down regulated and their re-expression re-sensitized CSCs to CDDP. This comprehensive review consolidates the compelling evidence that miRNAs are central regulators of CDDP response in CSCs. Understanding this intricate regulatory network provides a robust foundation for developing novel therapeutic strategies, such as miRNA-based mimics or inhibitors (anti-miRs) to overcome CDDP resistance in CSCs improve patient outcomes.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397276","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":"Autologous collagen-induced chondrogenesis versus mesenchymal stem cell therapy combined with high tibial osteotomy for medial knee osteoarthritis: a retrospective study.","authors":"Yun Hwan Kim, Bo Seung Bae, Jae Woong Jung, Chan Sik Kim, Seon Ae Kim, Mi-La Cho, Suo Kim, Sung Bin Sorn, Asode Ananthram Shetty, Jianmo Li, Seok Jung Kim","doi":"10.1186/s13287-026-05151-w","DOIUrl":"10.1186/s13287-026-05151-w","url":null,"abstract":"<p><strong>Background: </strong>Cartilage restoration techniques combined with high tibial osteotomy (HTO) have increasingly been used to delay conversion to total knee arthroplasty. Among these, autologous collagen-induced chondrogenesis (ACIC) and mesenchymal stem cell (MSC) therapy have gained significant research attention; however, their comparative therapeutic efficacy remains unclear.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 102 patients with medial compartment knee osteoarthritis who underwent HTO combined with cartilage repair (ACIC, n = 70; MSC, n = 32). Arthroscopic and radiographic parameters, including International Cartilage Repair Society (ICRS) grade, cartilage defect size, Kellgren-Lawrence (KL) grade, and mechanical alignment, were evaluated preoperatively and at second-look arthroscopy performed during hardware removal (mean, 27.2 ± 12.2 months). Clinical outcomes, including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and International Knee Documentation Committee Subjective Knee (IKDC) scores, were also assessed preoperatively and at the last clinical follow-up (mean, 58.11 ± 30.85 months).</p><p><strong>Results: </strong>ICRS grade significantly improved, and cartilage defect size significantly decreased in both groups (all p < 0.001). KL grade also showed significant postoperative improvement in both groups (p < 0.001). No significant differences were observed between groups in ICRS grade (p = 1.000), cartilage defect size (p = 0.202), and KL grade (p = 0.529). Both groups showed significant clinical improvements in WOMAC, VAS, and IKDC scores (all p < 0.001). There were no significant differences between the two groups in clinical outcomes (WOMAC, p = 0.430; VAS, p = 0.307; IKDC, p = 0.823).</p><p><strong>Conclusions: </strong>Both ACIC and MSC combined with HTO resulted in significant arthroscopic, radiographic, and clinical improvements in patients with varus knee osteoarthritis. No significant differences were observed, indicating comparable effectiveness of the two techniques when performed in conjunction with HTO.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397229","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}