Stem Cell Research & Therapy最新文献

{"title":"Lyophilized mesenchymal stromal cell-derived extracellular vesicles for the oral treatment of inflammatory bowel disease: a novel cell-free therapeutic strategy.","authors":"Shuangshuang Yang, Siyu Chen, Wenya Zhuang, Qiuhong Wang, Yi Xu, Taijie Zhan, Weifeng Huang, Yi Tan","doi":"10.1186/s13287-026-05033-1","DOIUrl":"https://doi.org/10.1186/s13287-026-05033-1","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. Current standard treatments, including aminosalicylates, corticosteroids, immunomodulators, and biologic therapies, can induce and maintain remission; however, a considerable proportion of patients show limited responsiveness or experience adverse effects. This highlights the urgent need for safer and more effective therapeutic alternatives. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) represent a promising cell-free therapeutic modality owing to their immunomodulatory and reparative capabilities. These vesicles replicate many of the therapeutic benefits of mesenchymal stromal cells (MSCs) while avoiding the risks associated with conventional cell-based treatments. Nevertheless, clinical translation of MSC-EVs for IBD management remains constrained by issues such as limited storage stability and invasive delivery routes.</p><p><strong>Methods: </strong>Extracellular vesicles (EVs) were isolated from the culture supernatant of human umbilical cord-derived MSCs via tangential flow filtration (TFF) followed by ultracentrifugation, and were characterized using transmission electron microscopy, western blotting, and nanoflow cytometry. To enhance their stability, MSC-EVs were lyophilized with trehalose and mannitol serving as cryoprotectants. The lyophilized powder was subsequently encapsulated in enteric-coated capsules for oral administration. The therapeutic efficacy of this formulation was evaluated in a dextran sulfate sodium (DSS)-induced rat colitis model. Disease activity was recorded daily, and post-experimental analyses included histopathology, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and serum biochemistry to evaluate hepatorenal function.</p><p><strong>Results: </strong>A robust lyophilization protocol was successfully established to enhance MSC-EV stability, along with an innovative oral delivery system for IBD therapy. In DSS-induced colitis rats, lyophilized MSC-EVs markedly alleviated disease severity, as indicated by a reduced disease activity index (DAI), preserved colon length, and improved histological architecture. MSC-EV administration restored intestinal barrier integrity, modulated cytokine expression profiles, mitigated systemic inflammation, and improved hepatic and renal function.</p><p><strong>Conclusions: </strong>This study demonstrated the therapeutic efficacy of a lyophilized, orally administered MSC-EV formulation in experimental colitis. This approach not only enhances vesicle stability and simplifies storage but also provides a non-invasive, patient-friendly route of administration. These findings underscore the strong translational potential of lyophilized MSC-EVs as a practical and effective cell-free therapeutic strategy for IBD.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781553","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":"Apelin-13 enhances BMSCs osteogenic differentiation and bone regeneration under hypoxia via upregulation of Ibsp.","authors":"Junming Tao, Xiaoning Qiu, Datian Fu, Si Wu, Zixing Wang, Chi Zhang, Mengru Hong, Shaochen Duan, Wei Jing","doi":"10.1186/s13287-026-05034-0","DOIUrl":"https://doi.org/10.1186/s13287-026-05034-0","url":null,"abstract":"<p><strong>Background: </strong>Apelin-13 plays a critical role in promoting angiogenesis and regulating cellular metabolism. However, the short half-life of Apelin-13 in vivo limits its further applications. Stem cell transplantation has been widely applied in tissue regeneration, but the low survival rate of transplanted stem cells in vivo restricts its therapeutic efficacy. This study aims to combine Apelin-13 with stem cell transplantation to enhance the survival rate of transplanted stem cells and promote bone regeneration.</p><p><strong>Methods: </strong>In this study, BMSCs and HUVEC were pretreated with different concentrations of Apelin-13 to investigate its effects on their proliferation, differentiation capacities under hypoxic conditions (1% O₂). A rat mandibular bone defect model was employed to evaluate the promotive effects of Apelin-13-BMSCs and Apelin-13-HUVEC transplantation on bone regeneration, and RNA sequencing together with a rat closed femoral fracture model was further used to explore the potential mechanisms by which Apelin-13 enhances BMSC proliferation and differentiation.</p><p><strong>Results: </strong>Apelin-13 enhances the proliferative and differentiation capacities of BMSCs and HUVEC under hypoxic conditions, reduces apoptosis, and exerts these promotive effects in a dose-dependent manner. BMSCs pretreated with Apelin-13 markedly facilitate the repair of rat mandibular bone defects and the healing of femoral fractures. Mechanistically, Apelin-13 promotes proliferation and osteogenic differentiation by upregulating Ibsp expression in BMSCs.</p><p><strong>Conclusion: </strong>BMSCs pretreated with Apelin-13 exhibited favorable regenerative and differentiation capacities in both in vitro and in vivo experiments, providing a potential strategy to address the challenges of low survival rates and stemness decline following stem cell transplantation in vivo.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781600","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":"Urine-derived stem cells in kidney disease: progress, challenges, and future directions.","authors":"Jasmine C L Atay, Anders Toftegaard Boysen, Rikke Nørregaard","doi":"10.1186/s13287-026-05040-2","DOIUrl":"https://doi.org/10.1186/s13287-026-05040-2","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a major global health burden with limited treatment options that address the underlying causes of fibrosis or promote regeneration. Urine-derived stem cells (USCs) have emerged as a promising tool in regenerative nephrology, offering a non-invasive and accessible source of multipotent cells with therapeutic potential. Sharing key properties with mesenchymal stem cells, USCs demonstrate paracrine activity, immunomodulation, and efficient extracellular vesicle (EV) production, and have shown anti-fibrotic, anti-inflammatory, and pro-regenerative effects in preclinical models of acute and chronic kidney injury. Recent advances in biomaterials and delivery technologies, including scaffold-free cell sheets and engineered EVs, have further enhanced the potential of USC-based therapies. However, challenges remain, particularly regarding functional integration, delivery optimization, and donor variability. This review summarizes the current progress in USC-based kidney therapy, identifies key limitations, and outlines future directions to support the translation of USC-based interventions into clinical practice.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781614","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":"iPSC-derived exosomes promote diabetic wound healing by attenuating inflammatory responses.","authors":"Li Long, Ju Qiao, Liang Wang, Yue Wang, Yi Xu, Hui Chen, Hongzhong Jin, Wei He, Xiaohong Han, Jianmin Zhang","doi":"10.1186/s13287-026-05005-5","DOIUrl":"https://doi.org/10.1186/s13287-026-05005-5","url":null,"abstract":"<p><strong>Background: </strong>Owing to impaired glucose metabolism, the high-glucose microenvironment in diabetic patients disrupts a series of biological reactions that hinder the wound healing process, resulting in a significant cost to the health care system and an urgent need for new and advanced therapies.</p><p><strong>Methods: </strong>In this study, induced pluripotent stem cell-derived exosomes (iPSC-Exos) were isolated from iPSC culture supernatant via centrifugation and ultrafiltration. We evaluated the therapeutic effects of iPSC-Exos on diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and streptozotocin (STZ)-induced diabetic mouse model). iPSC-Exos were topically administered to full-thickness cutaneous wounds in diabetic mice. The therapeutic effects were systematically assessed by measuring wound closure rates, conducting comprehensive histopathological evaluations, and performing quantitative analysis of inflammatory mediators via ELISA.</p><p><strong>Results: </strong>We demonstrated that iPSC-Exos can significantly accelerate diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and STZ-induced diabetic mouse model) for the first time. The multifaceted therapeutic mechanisms include: (ⅰ) Direct activation of tissue regeneration (promotion of re-epithelialization, tissue remodeling and scar attenuation); (ⅱ) Modulation of the inflammatory microenvironment (promoting macrophage polarization toward anti-inflammatory M2 phenotype/suppressing inflammation).</p><p><strong>Conclusions: </strong>This dual-animal model approach, which closely recapitulates key pathophysiological features of human diabetic wounds, offers superior clinical translatability compared to single-animal model studies. Our findings not only establish a robust scientific foundation for clinical development of iPSC-Exos therapy, but also present a transformative, cell-free treatment paradigm for chronic diabetic wounds that addresses critical unmet medical needs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781592","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":"Generation of functional mesothelial cells from human iPSCs that restore peritoneal integrity in experimental peritoneal injury.","authors":"Tadashi Kato, Mayu Yamashita, Masahiro Yasuda, Yutaro Ando, Ryusuke Nakatsuka, Yasumasa Shirouzu, Tatsuya Fujioka, Masayuki Tsukasaki, Fumiyuki Hattori, Yoshihiro Taniyama, Hiroaki Ogata, Akiko Sakashita, Hirokazu Honda, Hirofumi Hitomi","doi":"10.1186/s13287-026-05037-x","DOIUrl":"https://doi.org/10.1186/s13287-026-05037-x","url":null,"abstract":"<p><strong>Background: </strong>Long-term peritoneal injury results in loss of mesothelial integrity and impaired ultrafiltration, limiting the durability of peritoneal dialysis. Because primary human peritoneal mesothelial cells (PMCs) are difficult to obtain and expand, regenerative strategies for restoring peritoneal function have remained limited.</p><p><strong>Methods: </strong>We developed a protocol to differentiate human induced pluripotent stem cells (iPSCs) into functional peritoneal mesothelial-like cells (iPMCs). The molecular and functional characteristics of iPMCs were evaluated using gene expression analyses and functional assays, including comparison with a mesothelial cell model. The therapeutic effect of iPMCs was evaluated in a methylglyoxal-induced experimental peritoneal injury mouse model.</p><p><strong>Results: </strong>iPMCs exhibited typical cobblestone morphology and expressed key mesothelial markers including CK18, WT1 and MSLN. Transcriptomic analysis demonstrated strong similarity between iPMCs and primary PMCs. In vivo, intraperitoneal administration of iPMCs partially improved peritoneal transport parameters in a mouse model of peritoneal injury.</p><p><strong>Conclusions: </strong>We successfully generated functional mesothelial cells from human iPSCs that reproduce mesothelial-like functional properties and suggest potential for restoring peritoneal integrity. This study demonstrates the feasibility of iPSC-derived mesothelial cells as a regenerative cell source for peritoneal repair and provides a foundation for future peritoneal regeneration therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781634","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":"Therapeutic potential of mesenchymal stromal cells in COVID-19: a meta-analysis of clinical trials conducted since the pandemic onset.","authors":"Meng-Qi Yuan, Yue-Fei Pan, Zi-Ying Zhang, Ya-Xin Wu, Kai-Di Zhu, Ze-Rui Wang, Ze-Yi Zhang, Jia-Qi Xiong, Zhe Xu, Lei Huang, Fu-Sheng Wang, Lei Shi","doi":"10.1186/s13287-026-05020-6","DOIUrl":"https://doi.org/10.1186/s13287-026-05020-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n = 1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger's test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR = 0.74, 95% CI 0.55-0.99), with low heterogeneity (I&lt;sup&gt;2&lt;/sup&gt; = 2.8%, P =0.422[Q-test]) and no publication bias. The quality of evidence was moderate (according to the GRADE assessment). The subgroup analysis revealed a significant survival benefit in severe/critical patients (OR = 0.73, 95% CI 0.54-0.98) but not in studies that included moderate cases (OR = 0.91, 95% CI 0.23-3.65). No significant heterogeneity was found across study designs, administration routes, or dosing frequencies, which confirmed the robustness of the primary findings while indicating insufficient evidence to determine the optimal regimen. The secondary outcomes suggested improvements in clinical recovery, pulmonary function, and pro-/anti-inflammatory cytokine balance in patients that received MSC therapy. Limited studies with long-term follow-up indicated potential benefits for Long-COVID outcomes (e.g., fatigue, quality of life, residual CT abnormalities, and exercise tolerance). No significant differences were observed in AEs or SAEs post-MSC infusion, which suggested that MSC therapy was well tolerated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: ","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781629","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":"PW1⁺ cells give rise to cardiac adipocytes during development and myofibroblasts following injury.","authors":"Yuanxin Wei, Shan Kou, Lieyang Qin, Defang Deng, Wen Zhang, Jufeng Meng, Teng Feng, Chen Liu, Juan Tang, Hui Zhang","doi":"10.1186/s13287-026-05035-z","DOIUrl":"https://doi.org/10.1186/s13287-026-05035-z","url":null,"abstract":"<p><strong>Background: </strong>Pw1, a maternally imprinted gene, is expressed in various stem cell populations, underscoring its crucial roles in tissue development, maintenance, and regeneration. While our recent work has revealed its regulatory function in cardiac fibrosis following ischemic injury, whether PW1⁺ cells exhibit stem cell properties in the heart remains unclear.</p><p><strong>Methods: </strong>We utilized genetic lineage tracing with Pw1^pCreER/m+;R26-tdT and Pw1^p2A-CreER/m+;R26-tdT mouse models. The adipogenic and fibrogenic potential of PW1⁺ cells was assessed in vitro using sorted tdTomato⁺ cells subjected to differentiation assays. In vivo fate mapping was performed during postnatal development and after myocardial infarction (MI) induced by permanent coronary artery ligation. Single-cell RNA sequencing data from adult mouse hearts were reanalyzed to characterize Pw1 expression across cardiac cell types.</p><p><strong>Results: </strong>PW1 was expressed in multiple cardiac cell types-such as mesenchymal cells, epicardial cells, and endothelial cells-during early postnatal development. Isolated PW1⁺ cells from infant hearts differentiated into adipocytes in vitro, and lineage tracing experiments confirmed their significant contribution to cardiac adipocyte formation throughout postnatal development. Single-cell transcriptomic analysis further revealed predominant Pw1 expression in adult cardiac fibroblasts. In vitro, adult PW1⁺ cells differentiated into myofibroblasts upon TGFb1 stimulation and showed upregulated expression of extracellular matrix genes and TGFb receptors. After MI, PW1⁺ cells preferentially expanded and contributed to the myofibroblast population within the infarcted region.</p><p><strong>Conclusion: </strong>This study reveals that PW1⁺ cells serve as a progenitor population capable of generating cardiac adipocytes during postnatal development and contributing to myofibroblast formation after MI. These findings offer new insights into cardiac adipogenesis and fibrogenesis, providing a potential foundation for future therapies aimed at mitigating pathological adipose accumulation and fibrosis in the heart.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781570","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":"Phase-dependent efficacy of intravenous amniotic mesenchymal stem cells in a rat spinal cord injury model.","authors":"Yi Qi, Masahito Kawabori, Sho Yamaguchi, Yo Nakahara, Zheng Li, Sumio Ohtsuki, Miki Fujimura","doi":"10.1186/s13287-026-05018-0","DOIUrl":"https://doi.org/10.1186/s13287-026-05018-0","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury results in profound neurological disability driven initially by primary mechanical damage and subsequently by secondary injury processes characterized by progressive neuroinflammation. Intravenous administration of human amniotic mesenchymal stem cells (MSC) has emerged as a promising therapeutic approach; however, the optimal timing of administration and its relationship to dynamic immune responses remain unclear.</p><p><strong>Methods: </strong>A rat contusion model of spinal cord injury was used to evaluate the effects of intravenous MSC administration at three post-injury time points: days 1, 3, and 7. Functional and histological assessments were performed for each group. Systemic inflammatory responses were evaluated through blood analysis of neutrophil and macrophage counts, systemic inflammation index (SII), and plasma proteomics. Local immune responses were assessed by quantifying infiltrating immune cells within the injured spinal cord.</p><p><strong>Results: </strong>The most substantial improvement in locomotor function was observed in the day-1 treatment group, followed by the day-7 group, whereas the day-3 group showed minimal benefit. The day-3 group also demonstrated a trend toward greater lesion length and increased macrophage infiltration 28 days after injury. MSC administration reduced SII in the day-1 and day-7 groups but not in the day-3 group, which instead showed an increased systemic inflammatory response. Analysis of spinal cord tissue demonstrated that MSC treatment on day-1 effectively reduced neutrophil infiltration, which peaks at this time point, while day-7 administration reduced macrophage infiltration during its peak phase. In contrast, MSC administration on day-3 failed to attenuate either neutrophil or macrophage accumulation. Plasma proteomic profiling revealed enhanced complement and coagulation pathway activation specifically on day-3.</p><p><strong>Conclusions: </strong>The therapeutic efficacy of intravenously administered MSC is highly dependent on the timing of intervention. Optimal benefit is achieved when treatment coincides with peak activation of a dominant target immune cell population and avoids the peak of complement and coagulation signaling. These findings support a phase-matched therapeutic strategy to maximize MSC effectiveness following spinal cord injury.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781651","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":"IL-1β modulates inflammatory response of human bone marrow-derived MSCs and neutrophil recruitment in vitro via NF-kB-associated signaling.","authors":"Nour Hassaan, Tobias Schmidt, Zackarias Söderlund, Dimitrios Kalafatis, Lisa I Påhlman, Stefan Scheding, Daniel J Weiss, Robin Kahn, Sara Rolandsson Enes","doi":"10.1186/s13287-026-05029-x","DOIUrl":"https://doi.org/10.1186/s13287-026-05029-x","url":null,"abstract":"<p><strong>Background: </strong>The variable clinical outcomes of mesenchymal stromal cell (MSC)-based therapy in acute respiratory distress syndrome (ARDS) are attributed to a variety of factors, including host microenvironmental factors. Interleukin-1β (IL-1β) has been linked to the development and progression of ARDS, and we have previously found that IL-1β could be used to predict MSC activation in vitro. However, the exact mechanisms through which IL-1β alters the MSC function and its interaction with the host immune cells remains unknown. Therefore, the aim of this study was to assess how IL-1β alters MSC function, with a specific focus on MSC-neutrophil interaction.</p><p><strong>Methods: </strong>Human bone marrow-derived MSCs were exposed to 20 ng/ml IL-1β for 1 or 24 h. Following exposure, MSCs were analyzed using bulk RNA sequencing and key secretome proteins were measured in their conditioned medium. A transwell culture system was used to evaluate the neutrophil recruitment capacity of IL-1β-exposed MSCs, with or without NF-kB inhibition. MSCs exposed to serum free medium were used as controls in all experiments.</p><p><strong>Results: </strong>The sequencing data revealed that genes involved in response to biotic stimuli and immune response were altered in MSCs exposed to IL-1β compared to control cells. In particular, genes essential for neutrophil recruitment were significantly upregulated after IL-1β exposure. The functional in vitro studies further validated these results, demonstrating that MSCs exposed to IL-1β had a significantly higher neutrophil recruitment capacity compared to unstimulated MSCs. Finally, inhibition of the NF-kB pathway resulted in a significant decrease of the MSC's capacity to recruit neutrophils to levels similar as to the unstimulated control MSCs.</p><p><strong>Conclusion: </strong>These data provide mechanistic insight into how inflammatory factors present in the host microenvironment might affect the interaction between MSCs and immune cells. This further highlights the need to understand the MSC mode of action, and to map out how the MSC fate might change in different host environments after administration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781635","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":"Investigation of the clinical efficacy of mesenchymal stem cells in combination with monoclonal antibody therapy against feline panleukopenia.","authors":"Yi Wang, Rui Yan, Ling Mao, Huikang Wang, Cong Zhu, Difei Wang, Yi Ding, Dengru Wang","doi":"10.1186/s13287-026-04967-w","DOIUrl":"https://doi.org/10.1186/s13287-026-04967-w","url":null,"abstract":"<p><strong>Background: </strong>Feline panleukopenia is an acute and highly contagious disease caused by feline panleukopenia virus (FPV). Conventional therapeutic approaches often yield suboptimal outcomes in managing leukopenia, which consequently contributes to its high mortality rate. Mesenchymal stem cells (MSCs) are a type of multipotent stem cell characterized by their multidirectional differentiation potential and immunomodulatory capabilities. Studies have shown that MSCs possess the potential to treat inflammatory and immune-mediated diseases, support and promote hematopoiesis, and facilitate tissue repair. Therefore, this study was to investigate the clinical efficacy of combining MSCs with feline panleukopenia monoclonal antibody to propose a potential treatment for FPV.</p><p><strong>Method: </strong>MSCs were extracted from a newborn kitten's umbilical cord tissue. Fifteen healthy unimmunized kittens aged 2 to 4 months were divided evenly into three groups: control group, conventional treatment group, and MSCs group (conventional treatment combined with MSCs therapy, involving daily intravenous administration of 1 × 10⁷ MSCs for 3 consecutive days). Treatments were commenced once evident clinical symptoms manifested and white blood cell counts declined below the normal range. The subject cats were assessed for clinical signs, complete blood count (CBC), blood biochemistry, serum amyloid A (SAA), pathology and viral load in major organs.</p><p><strong>Result: </strong>The results revealed that in the control group and conventional treatment group, cats exhibited a rapid decline in white blood cell count following disease onset, ultimately resulting in mortality. Conversely, in the MSCs group, four cats demonstrated an increase in white blood cell count post-treatment, subsequently returning to normal levels. However, one cat did not exhibit a significant increase and died on the third day of treatment.</p><p><strong>Conclusion: </strong>These findings highlight the therapeutic potential of MSCs in elevating leukocyte counts, improving clinical symptoms, and ultimately leading to a significant enhancement of survival rates among FPV-affected cats.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147780250","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}