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However, long-term use increases the risk of infection and tumors for their systemic inhibition of TNF-\u03b1, which disrupts the regular physiological function of this molecular. Mesenchymal stem cells (MSCs)-based delivery system provides new options for RA treatment with their \u201choming\u201d and immune-regulation capacities, whereas inflammatory environment (especially TNF-\u03b1) is not conducive to MSCs' therapeutic effects by inducing apoptosis\/autophagy. Here, we constructed a strain of sTNFRII-Fc-expressing MSCs (sTNFRII-MSC), aiming to offset the deficiency of those two interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Constructed sTNFRII-Fc lentiviral vector was used to infect human umbilical cord-derived MSCs, and sTNFRII-MSC stable cell line was generated by monoclonal cultivation. In vitro and vivo characteristics of sTNFRII-MSC were assessed by coculture assay and an acute inflammatory model in NOD\/SCID mice. The sTNFRII-MSC were transplanted into CIA model, pathological and immunological indicators were detected to evaluate the therapeutic effects of sTNFRII-MSC. The distribution of sTNFRII-MSC was determined by immunofluorescence assay. Apoptosis and autophagy were analyzed by flow cytometry, western blot and immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>sTNFRII-Fc secreted by sTNFRII-MSC present biological activity both in vitro and vivo. sTNFRII-MSC transplantation effectively alleviates mice collagen-induced arthritis (CIA) via migrating to affected area, protecting articular cartilage destruction, modulating immune balance and sTNFRII-MSC showed prolonged internal retention via resisting apoptosis\/autophagy induced by TNF-\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>sTNFRII-Fc modification protects MSCs against apoptosis\/autophagy induced by TNF-\u03b1, in addition to releasing sTNFRII-Fc neutralizing TNF-\u03b1 to block relevant immune-inflammation cascade, and thus exert better therapeutic effects in alleviating inflammatory arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-021-02602-4","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T16:16:23Z","timestamp":1633882583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["sTNFRII-Fc modification protects human UC-MSCs against apoptosis\/autophagy induced by TNF-\u03b1 and enhances their efficacy in alleviating inflammatory arthritis"],"prefix":"10.1186","volume":"12","author":[{"given":"Yingjie","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueye","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-9598","authenticated-orcid":false,"given":"Wei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"2602_CR1","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","volume":"388","author":"JS Smolen","year":"2016","unstructured":"Smolen JS, Aletaha D, McInnes IB. 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