{"title":"BMSC-derived exosomes improve rheumatoid arthritis by regulating Th17 cell differentiation through targeting PRDM1.","authors":"Shaomin Chen, Xinxin Li, Yang Shen, Shichong Lin, Xiaolong Shui, Hua Zhu","doi":"10.1080/17460751.2025.2469426","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is categorized as an autoimmune condition. Bone marrow-derived mesenchymal stromal cell (BMSC) derived exosome (BMSC-Exo) exert vital character in RA. We aimed to investigate the regulatory mechanism of BMSC-Exo in alleviating RA.</p><p><strong>Methods: </strong>BMSC was isolated from mouse bone marrow. Collagen-induced arthritis (CIA) was induced by injecting bovine type II collagen and complete Freund's adjuvant. Arthritis score, incidence, and withdrawal threshold were assessed. Hematoxylin-eosin staining was used to observe knee joint damage. CD4<sup>+</sup> T cells were isolated from the spleen, and T helper 17 (Th17) proportions were measured by flow cytometry. Caspase-1 activity was assessed.</p><p><strong>Results: </strong>BMSC-Exo injection reduced arthritis score and incidence of arthritis, and elevated the withdrawal threshold of CIA mice. BMSC-Exo also alleviated knee damage in CIA mice and reduced the Th17 proportion. BMSC-Exo down-regulated inflammatory cytokine levels, as well as caspase-1 activity. BMSC-Exo up-regulated PR Domain Zinc Finger Protein 1 (PRDM1) levels. PRDM1 knockdown in BMSC down-regulated PRDM1 expression in Exo but did not affect up-regulated PRDM1 expression in CD4<sup>+</sup> T cells. In vivo, BMSC-Exo affected RA pathology by acting on PRDM1.</p><p><strong>Conclusions: </strong>BMSC-Exo improved RA by promoting PRDM1 expression in CD4<sup>+</sup> T cells and inhibiting Th17 cell differentiation.</p>","PeriodicalId":21043,"journal":{"name":"Regenerative medicine","volume":" ","pages":"35-44"},"PeriodicalIF":2.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881839/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regenerative medicine","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1080/17460751.2025.2469426","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/1 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
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Abstract
Background: Rheumatoid arthritis (RA) is categorized as an autoimmune condition. Bone marrow-derived mesenchymal stromal cell (BMSC) derived exosome (BMSC-Exo) exert vital character in RA. We aimed to investigate the regulatory mechanism of BMSC-Exo in alleviating RA.
Methods: BMSC was isolated from mouse bone marrow. Collagen-induced arthritis (CIA) was induced by injecting bovine type II collagen and complete Freund's adjuvant. Arthritis score, incidence, and withdrawal threshold were assessed. Hematoxylin-eosin staining was used to observe knee joint damage. CD4+ T cells were isolated from the spleen, and T helper 17 (Th17) proportions were measured by flow cytometry. Caspase-1 activity was assessed.
Results: BMSC-Exo injection reduced arthritis score and incidence of arthritis, and elevated the withdrawal threshold of CIA mice. BMSC-Exo also alleviated knee damage in CIA mice and reduced the Th17 proportion. BMSC-Exo down-regulated inflammatory cytokine levels, as well as caspase-1 activity. BMSC-Exo up-regulated PR Domain Zinc Finger Protein 1 (PRDM1) levels. PRDM1 knockdown in BMSC down-regulated PRDM1 expression in Exo but did not affect up-regulated PRDM1 expression in CD4+ T cells. In vivo, BMSC-Exo affected RA pathology by acting on PRDM1.
Conclusions: BMSC-Exo improved RA by promoting PRDM1 expression in CD4+ T cells and inhibiting Th17 cell differentiation.
期刊介绍：
Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function*. Since 2006, Regenerative Medicine has been at the forefront of publishing the very best papers and reviews covering the entire regenerative medicine sector. The journal focusses on the entire spectrum of approaches to regenerative medicine, including small molecule drugs, biologics, biomaterials and tissue engineering, and cell and gene therapies – it’s all about regeneration and not a specific platform technology. The journal’s scope encompasses all aspects of the sector ranging from discovery research, through to clinical development, through to commercialization. Regenerative Medicine uniquely supports this important area of biomedical science and healthcare by providing a peer-reviewed journal totally committed to publishing the very best regenerative medicine research, clinical translation and commercialization.
Regenerative Medicine provides a specialist forum to address the important challenges and advances in regenerative medicine, delivering this essential information in concise, clear and attractive article formats – vital to a rapidly growing, multidisciplinary and increasingly time-constrained community.
Despite substantial developments in our knowledge and understanding of regeneration, the field is still in its infancy. However, progress is accelerating. The next few decades will see the discovery and development of transformative therapies for patients, and in some cases, even cures. Regenerative Medicine will continue to provide a critical overview of these advances as they progress, undergo clinical trials, and eventually become mainstream medicine.
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