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It is well known that mesenchymal stem cells (MSCs) are a promising therapy partly due to their paracrine-mediated immunoregulatory function. Previous study demonstrated that transforming growth factor-beta1 (TGF-\u03b21) is an important cytokine secreted by MSCs and that it participates in MSC-mediated macrophage phenotype switch from pro-inflammatory to pro-resolution. In addition, the transformation of macrophage phenotype may be a potential treatment for sepsis. However, the therapeutic effect of overexpressing TGF-\u03b21 in MSCs (MSC-TGF-\u03b21) on sepsis is not well understood. Therefore, this study aimed to evaluate the effects of TGF-\u03b21 overexpressing MSCs on organ injury in cecal ligation and puncture (CLP)-induced septic mice and to detect the changes in macrophage phenotype during this process.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Mouse MSCs stably transfected with TGF-\u03b21 were constructed and injected into CLP-induced septic mice via tail vein. After 24\u2009h, the mice were sacrificed; then, the histopathology of the organ was evaluated by hematoxylin-eosin (H&amp;E) staining. Inflammatory cytokines were detected by ELISA. Macrophage infiltration and phenotype transformation in the tissues were determined by immunohistochemistry and flow cytometry. In addition, we performed adoptive transfer of mouse peritoneal macrophage pretreated with TGF-\u03b21 overexpressing MSCs in septic mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that infusion of TGF-\u03b21 overexpressing MSCs attenuated the histopathological impairment of the organ, decreased the pro-inflammatory cytokine levels and inhibited macrophage infiltration in tissues. TGF-\u03b21 overexpressing MSCs induced macrophage phenotypes changed from pro-inflammatory to pro-resolution in inflammatory environment. The adoptive transfer of mouse peritoneal macrophages pretreated with TGF-\u03b21 overexpressing MSCs also relieved organ damage in CLP-induced septic mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Under septic conditions, TGF-\u03b21 overexpressing MSCs can enhance the therapeutic effects of MSCs on organ injury and inflammation as a result of reduced macrophage infiltration and induced macrophages transformation, the adoptive transfer of macrophages treated with TGF-\u03b21 overexpressing MSCs also relieved organ damage. This will provide new hope for the treatment of sepsis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-020-01894-2","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T09:03:57Z","timestamp":1599123837000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Overexpressing TGF-\u03b21 in mesenchymal stem cells attenuates organ dysfunction during CLP-induced septic mice by reducing macrophage-driven inflammation"],"prefix":"10.1186","volume":"11","author":[{"given":"Feng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongsheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"1894_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","volume":"392","author":"M Cecconi","year":"2018","unstructured":"Cecconi M, Evans L, Levy M, et al. 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