Current stem cell research & therapy最新文献

{"title":"Immunomodulatory Roles of Mesenchymal Stem Cell-derived Extracellular Vesicles: A Promising Therapeutic Approach for Autoimmune Diseases.","authors":"Prince Ahad Mir, Md Sadique Hussain, Murtaza Ahmad Khanday, Roohi Mohi-Ud-Din, Faheem Hyder Pottoo, Reyaz Hasssan Mir","doi":"10.2174/011574888X341781241216044130","DOIUrl":"https://doi.org/10.2174/011574888X341781241216044130","url":null,"abstract":"<p><p>Autoimmune diseases pose a significant challenge due to their complex pathogenesis and rising prevalence. Traditional therapies are often limited by systemic side effects, immunosuppression, and lack of long-term efficacy. Mesenchymal stem cells (MSCs) have demonstrated immunomodulatory properties, primarily through the secretion of extracellular vesicles (EVs), which are now recognized as potent mediators of immune regulation. MSC-derived EVs carry bioactive molecules such as microRNAs, proteins, and lipids that influence key immune pathways, making them a promising therapeutic avenue for autoimmune diseases. This review critically examines the immunomodulatory mechanisms of MSC-derived EVs, focusing on their role in regulating T cells, B cells, and macrophages, which are central to autoimmune pathology. We explore recent preclinical and clinical studies that highlight the ability of MSC-derived EVs to reduce inflammation, promote immune tolerance, and restore tissue homeostasis in autoimmune settings. Furthermore, we discuss the advantages of EV-based therapy over MSC-based therapies, including improved safety profiles, lower immunogenicity, and scalability for clinical application. By evaluating the current landscape of MSC-derived EV research, we identify key gaps and propose innovative strategies to optimize EVbased therapies for autoimmune diseases. These strategies include engineering EVs to enhance their specificity and therapeutic efficacy, as well as integrating them with biomaterials for targeted delivery. Our review aims to provide a forward-looking perspective on the potential of MSC-derived EVs as a novel therapeutic approach, moving beyond traditional cell-based therapies to offer more precise and personalized treatment options for autoimmune diseases.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraarticular Injection of Stem Cell and Related Exosome Targeting Synovial Macrophages in Osteoarthritis.","authors":"Zheng Li, Yuanchi Huang, Weisong Zhang, Wensen Jing","doi":"10.2174/011574888X338318241213055616","DOIUrl":"https://doi.org/10.2174/011574888X338318241213055616","url":null,"abstract":"<p><p>Osteoarthritis is a costly and debilitating condition, especially as the population ages and more people are affected. The primary osteoarthritis targets in the joint cavity are chondrocytes and synovial cells. Researchers are increasingly convinced that macrophages play a crucial role in the development or therapy of osteoarthritis despite being largely ignored in earlier studies due to their capacity to switch from a pro-inflammatory to an anti-inflammatory phenotype. Stem cell or similar extracellular vesicle intraarticular injection offers fresh promise for treating osteoarthritis. However, the mechanism by which this works needs further investigation. It is important to investigate the intricate cellular interactions between mesenchymal stem cells (MSCs) and macrophages. Emerging routes using extracellular vesicles (EVs) are garnering more and more attention in intercellular communication, which has historically focused on cytokines and soluble mediators. Therefore, we focus on the polarization of macrophages as a primary consideration in our study of stem cells and associated EVs utilization in treating knee osteoarthritis.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic Training Alleviates Muscle Atrophy by Promoting the Proliferation of Skeletal Muscle Satellite Cells in Myotonic Dystrophy Type 1 by Inhibiting Glycolysis via the Upregulation of MBNL1.","authors":"Hui-Qi Wang, Min Guo, Jie-Qiong Lu, Ling-Yun Chen, Feng Liang, Peng-Peng Huang, Kai-Yi Song","doi":"10.2174/011574888X360503241214045130","DOIUrl":"10.2174/011574888X360503241214045130","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle atrophy in myotonic dystrophy type 1 (DM1) is caused by abnormal skeletal muscle satellite cell (SSC) proliferation due to increased glycolysis, which impairs muscle regeneration. In DM1, RNA foci sequester muscleblind-like protein 1 (MBNL1) in the nucleus, inhibiting its role in regulating SSC proliferation. Aerobic training reduces glycolysis and increases SSC proliferation and muscle fiber volume. This study aimed to investigate whether aerobic training prevents muscle atrophy in DM1 through the regulation of glycolysis via MBNL1.</p><p><strong>Methods: </strong>In this study, we used the HSALR transgenic mice (DM1 mice model) to investigate the effects of aerobic training on skeletal muscle atrophy and its molecular mechanisms. HSALR mice were subjected to 4 weeks of aerobic training. After aerobic training, hindlimb grip, and myofiber mean cross-sectional area (CSA) detected by haematoxylin and eosin (HE) staining were performed. In DM1 primary SSCs, cell proliferation was assessed using Pax7 and MyoD immunofluorescence and CCK-8 assays, RNA foci were detected by RNA fluorescence in situ hybridization, and total MBNL1 expression was measured by western blot. We also used lentivirus to knock down MBNL1 in DM1 primary SSCs and performed RNA sequencing and extracellular acidification rate (ECAR). Furthermore, glycolysis detected by ECAR and oxygen consumption rate (OCR) assays were performed in WT, Sedentary, and Training group SSCs. Glycolysis was inhibited with shikonin, a glycolysis inhibitor, and the proliferation of DM1 SSCs was subsequently evaluated. Finally, we engineered an adeno-associated virus specifically targeting MBNL1 to knock down MBNL1 in DM1 mice. Subsequently, we assessed hindlimb grip strength and CSA in vivo, as well as the glycolytic capacity and proliferative capacity of DM1 SSCs in vitro.</p><p><strong>Results: </strong>Aerobic training increased hindlimb grip strength and the average myofiber CSA in DM1 mice. Additionally, aerobic training reduced RNA foci, upregulated MBNL1, and promoted SSC proliferation. Gene-set enrichment analysis (GSEA) indicated that glycolytic processes were enriched following the knockdown of MBNL1. Furthermore, ECAR showed glycolysis was enhanced after the knockdown of MBNL1. Aerobic training reduced elevated glycolysis in DM1 mice and primary SSCs. Treatment with shikonin promoted DM1 SSC proliferation. However, MBNL1 knockdown was shown to abolish the reduced glycolysis and increased proliferation capability of SSCs due to aerobic training.</p><p><strong>Conclusion: </strong>Taken together, aerobic training suppresses glycolysis in SSCs via the upregulation of MBNL1, thereby enhancing SSC proliferation and alleviating muscle atrophy.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cells Derived From Human Deciduous Exfoliated Teeth Ameliorate Adriamycin-Induced Nephropathy In Rats By Modulating The Th17/Treg Balance.","authors":"Yuyang Dai, Borui Tang, Xiuli Zhao","doi":"10.2174/011574888X336035241209065513","DOIUrl":"https://doi.org/10.2174/011574888X336035241209065513","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic Nephrotic Syndrome (INS) is a common kidney disease in children, and the main clinical manifestations are hypoproteinaemia, proteinuria, hyperlipidaemia, and oedema. Mesenchymal Stem Cells (MSCs) are involved in tissue repair, protection against fibrosis, and immune modulation but have rarely been studied in INS.</p><p><strong>Objective: </strong>This study aimed to explore the therapeutic potential of stem cells derived from human exfoliated deciduous teeth (SHEDs) in INS using an adriamycin-induced nephropathy (AN) rat model.</p><p><strong>Methods: </strong>AN was induced in Sprague‒Dawley rats, and SHEDs were transplanted via the tail vein in single (SHED-s) and multidose (SHED-m) regimens. Cell migration assays were used to track the SHED distribution. Weight, urine protein, and serum biochemical assays were also performed. HE and Masson staining were used to observe glomerular and tubular damage, as well as the degree of fibrosis. Immunohistochemistry was used to label T lymphocytes and podocytes, and structural changes in podocytes were observed by electron microscopy. ELISA was used to measure the levels of inflammatory factors. Flow cytometry was used to analyse the balance of Th17 cells and Tregs. The mRNA expression of Th17- and Treg-associated cytokines and specific transcription factors was examined by RT‒PCR.</p><p><strong>Results: </strong>SHEDs directly migrated to damaged tissues, suggesting a targeted therapeutic effect. SHED transplantation significantly reduced proteinuria and reversed biochemical abnormalities in rats with AN. Both single and multidose SHED treatments could inhibit glomerular and tubular damage and delay the progression of fibrosis caused by adriamycin. SHEDs exerted a protective effect on podocytes. Additionally, this treatment inhibited inflammatory responses and corrected immune imbalances, as evidenced by decreased T lymphocyte infiltration, reduced serum levels of IL-6, TNF-a, and IL-1β, and modulation of the Th17/Treg balance.</p><p><strong>Conclusion: </strong>In the AN rat model, SHED partly suppressed the development of inflammation and alleviated kidney injury, and immune regulation may be the underlying mechanism.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inducing Neural Fate: The Impact of Phenylacetate and Calcium on Human Adipose-Derived Mesenchymal Stem Cells Differentiation.","authors":"Mohsen Ghiasi, Mohammad Hajipur, Marzieh Ghollasi, Abdolreza Dayani, Mohammad-Taher Moradi, Ali Salimi","doi":"10.2174/011574888X355333241203114713","DOIUrl":"https://doi.org/10.2174/011574888X355333241203114713","url":null,"abstract":"<p><strong>Introduction: </strong>Human adipose-derived stem cells (hADSCs) are considered a promising source for cell replacement therapy in degenerative and traumatic conditions. This study explores the effects of phenylacetate and calcium on the neural differentiation of hADSCs for regenerative medicine. We assessed cell viability and cytotoxicity using the MTT assay, revealing that treatment with 1μM phenylacetate significantly enhanced cell viability compared to control groups over five days, while higher concentrations resulted in cytotoxic effects.</p><p><strong>Method: </strong>Additionally, qualitative analysis through Acridine orange/ethidium bromide (AO/EB) staining indicated normal cellular characteristics at lower phenylacetate concentrations, whereas higher doses led to observable cell death. A subsequent evaluation of intracellular calcium levels demonstrated a significant increase when hADSCs were treated with both phenylacetate and calcium.</p><p><strong>Results: </strong>The neural differentiation potential was further assessed through the relative quantification of neuronal-specific genes, showing marked upregulation of NSE, Oligo-2, β-tubulin III, and MAP-2 in all treatment groups compared to controls. Immunohistochemistry confirmed elevated protein expression of neural markers in cultures supplemented with phenylacetate and calcium.</p><p><strong>Conclusion: </strong>These findings suggest that phenylacetate, particularly in conjunction with calcium, enhances the neural differentiation of hADSCs, highlighting its potential utility in regenerative medicine strategies targeting neurodegenerative conditions.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing the Mesenchymal Stem Cell Aging through In silico Assessment of Extracellular Vesicle-mediated miRNAs.","authors":"Ningning Mi, Xibin Liu, Yuhua Gao, Chunyu Bai, Xiangchen Li","doi":"10.2174/011574888X342545241202050636","DOIUrl":"https://doi.org/10.2174/011574888X342545241202050636","url":null,"abstract":"<p><strong>Introduction: </strong>During mesenchymal stem cell (MSCs) aging, a decrease in its proliferation and regenerative capacity occurs, which is implicated in human aging. The MSCs aging process is regulated by genetics, metabolism, the external environment, and various complex pathways.</p><p><strong>Method: </strong>The aging of MSCs during in vitro culture poses a major challenge for developing cell therapy aimed at combating human diseases and aging. To identify the contributing factors underlying MSCs aging, we obtained datasets of mRNA expression changes before and after aging from the Gene Expression Omnibus (GEO) database and datasets of extracellular vesicles (EVs) microRNAs (miRNAs) expression changes (GSE153752, GSE195634, and GSE226464). We conducted an indepth analysis to screen the correlation between EVs-miRNAs and MSCs aging.</p><p><strong>Result: </strong>Our analysis identified significant differences in the expression of hsa-miR-146a-5p, hsamiR- 432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p in EVs before and after MSCs aging. These differences arise from the post-MSCs aging activation of signaling pathways, such as FOXO and P53, which promote the expression of hsa-miR-146a-5p, hsa-miR-432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p.</p><p><strong>Conclusion: </strong>Subsequently, these miRNAs are transported to EVs upon binding to the RNA-binding proteins A2BP1, SFRS2, MBNL1, EIF4B, and ACO1. This study used the correlation between MSCs aging and specific EVs-miRNAs to predict MSCs aging during the culture process.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cells: An Effective Therapy Regime for Oral Cancer.","authors":"Thangavel Lakshmipriya, Subash C B Gopinath","doi":"10.2174/011574888X358204241208161841","DOIUrl":"https://doi.org/10.2174/011574888X358204241208161841","url":null,"abstract":"","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CT-Guided Foramen Ovale Injection of Mesenchymal Stem Cells: First Human Case Report of Trigeminal Neuralgia Relief.","authors":"Kenneth Candido, Chadwick Prodromos, Kristian Nenchev","doi":"10.2174/011574888X335230241111061649","DOIUrl":"https://doi.org/10.2174/011574888X335230241111061649","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Trigeminal Neuralgia (TN) is an extremely painful condition without an established treatment other than symptom-suppressive medications or temporary relief from corticosteroid injections. Mesenchymal Stem Cells (MSCs) have demonstrated the ability to enhance healing and reduce inflammation and pain without side effects. Our objective was to evaluate the safety and efficacy of CT-guided foramen ovale MSC injection in the treatment of TN.</p><p><strong>Methods: </strong>A 48-year-old woman presented with a 22-year history of severe TN. Previous treatments, including microvascular decompression, acupuncture, chiropractic adjustment, and hypnotism had failed. Medications decreased pain, but produced severe bothersome mental clouding. After proper informed consent, the patient elected trigeminal nerve injection in the foramen ovale with AlloRx (vitrobiopharma.com Golden Colorado) umbilical cord-derived Mesenchymal Stem Cells (MSCs). An experienced pain specialist with previous experience using CT guidance with sedation to inject the trigeminal nerve in the foramen ovale with corticosteroids performed the injection using 20 million MSCs. The patient reported no adverse events or complications related to the treatment.</p><p><strong>Results: </strong>At 1 month post-treatment, the patient reported dramatically reduced pain/tingling, and no longer needed medication, which resulted in the resolution of her mental clouding. At 12 months post-treatment, some symptoms recurred, but the patient maintained substantial cognitive improvements and required a reduced dose of medication.</p><p><strong>Conclusion: </strong>We have demonstrated, for the first time, CT-guided MSC injection into the foramen ovale to result in significant improvement in trigeminal neuralgia without side effects.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Zhengsui Wan in the Treatment of Acute Lymphoblastic Leukemia Based on Network Pharmacology and Experimental Validation.","authors":"Xiangdong Yang, Fujun Yang, Pengying Yuan, Juan Xie, Lijun Fang, Weilong Sun, Xia Tao, Dixuan Li, Chenyang Fan, Ning Ji","doi":"10.2174/011574888X327937241129062944","DOIUrl":"https://doi.org/10.2174/011574888X327937241129062944","url":null,"abstract":"<p><strong>Background: </strong>Zhengsui Wan (ZSW) is a commonly used traditional Chinese medicine formula for treating Acute Lymphatic Leukemia (ALL) in our institution, and it has shown potential efficacy. However, its mechanism of action (MoA) remains unclear. In this study, we systematically explored the ZSW in ALL (in vitro and in vivo) using network pharmacology and molecular docking techniques.</p><p><strong>Methods: </strong>Mass spectrometry was conducted to analyze possible active components in ZSW. BALB/c mice were treated by ZSW aqueous decoction, and mesenchymal stem cells (MSCs) were extracted for proteomic analysis to evaluate differentially expressed proteins. Moreover, proteins associated with acute lymphoblastic leukemia in SwissTargetPrediction and GeneCards databases were screened, and they intersected with differentially expressed proteins to obtain potential targets for ZSW. Protein interactions were constructed for the selected targets. Then, we performed GO and KEGG enrichment analysis on its basis and screened the core target through K-core. We validated it by molecular docking with the top three actives in the molecular network in degree value. Finally, we detected the regulation of ICAM1 in MSCs by ZSW by qRT-PCR.</p><p><strong>Results: </strong>We detected 182 active ingredients in ZSW and identified 725 differential proteins in ZSWtreated mice, of which 25 were potential targets. Furthermore, MMP2, ICAM1, PSEN1, SLC9A1, and MMP14 were identified as core targets using the PPI network and K-core screening. Moreover, ZSW significantly downregulated ICAM1 expression in MSCs. GO and KEGG enrichment analyses showed that the results of ZSW were coordinated through immunomodulatory, inflammation-related, and drug resistance-related genes, including the PI3K-Akt, cAMP, and Wnt signaling pathways. Molecular docking and molecular dynamics simulations indicated moderate binding capacity between the active compounds and the screened target.</p><p><strong>Conclusion: </strong>In this study, we successfully identified possible active ingredients and predicted potential targets and pathways for ZSW for the treatment of ALL. We provide a new strategy for further research on the molecular basis of ZSW biological effects in ALL. In addition, the potential active ingredients could provide new leads for drug discovery in ALL investigations.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of miR-98/IL-6/STAT3 on Autophagy and Apoptosis of Cardiac Stem Cells Under Hypoxic Conditions In vitro.","authors":"Xueyuan Li, Yang Zhang, Guangwei Zhang","doi":"10.2174/011574888X294637240517050849","DOIUrl":"https://doi.org/10.2174/011574888X294637240517050849","url":null,"abstract":"<p><strong>Background: </strong>The heavy burden of cardiovascular diseases demands innovative therapeutic strategies dealing with cardiomyocyte loss. Cardiac Stem Cells (CSCs) are renewable cells in the myocardium with differentiation and endocrine functions. However, their functions are significantly inhibited in conditions of severe hypoxia or inflammation. The mechanism of hypoxia affecting CSCs is not clear. Interleukin-6 (IL-6) appears active in both hypoxic and inflammatory microenvironments. The aim of this study was to explore whether IL-6 is related to CSC apoptosis and autophagy under severe hypoxia.</p><p><strong>Methods: </strong>In this study, rat CSCs were extracted by alternate digestion. The interaction of miR-98 and IL-6 mRNA was detected by the dual luciferase method, and qPCR was applied to confirm the effect of miR-98 on IL-6 expression. The effect of IL-6 on CSC apoptosis was measured by flow cytometry and the effect of IL-6 on CSC autophagy by transmission electron microscopy. The western blot method was applied to detect the effect of IL-6 on the expressions of proteins related to apoptosis and autophagy. ANOVA and Dunnett T3's test were employed in the statistical analysis. When p < 0.05, the difference was significant.</p><p><strong>Results: </strong>Under severe hypoxia conditions, IL-6 increased CSC apoptosis and decreased p-STAT3 expression significantly. CSC apoptosis increased significantly after inhibition of the STAT3 signaling pathway under severe hypoxia. IL-6 could also significantly inhibit CSCs' autophagy and block their autophagy flow under severe hypoxic conditions. Meanwhile, it was confirmed that miR-98 had a binding site on IL-6 mRNA and miR-98 significantly inhibited IL-6 mRNA expression in CSCs under severe hypoxic conditions.</p><p><strong>Conclusion: </strong>miR-98/IL-6/STAT3 has been found to be involved in the regulation of CSCs' apoptosis and autophagy under severe hypoxic conditions and there might be a mutual linkage between CSCs' apoptosis and their autophagy.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}