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Human umbilical cord mesenchymal stem cell (hUCMSC) therapy has emerged as a novel treatment alternative for the treatment of DLC. However, optimized therapy protocols and the associated mechanisms are not entirely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We constructed a DLC rat model consistent with the typical clinical characteristics combined use of PB and CCL\n                      <jats:sub>4<\/jats:sub>\n                      . Performing dynamic detection of liver morphology and function in rats for 11\u00a0weeks, various disease characteristics of DLC and the therapeutic effect of hUCMSCs on DLC in experimental rats were thoroughly investigated, according to ascites examination, histopathological, and related blood biochemical analyses. Flow cytometry analysis of rat liver, immunofluorescence, and RT-qPCR was performed to examine the changes in the liver immune microenvironment after hucMSCs treatment. We performed RNA-seq analysis of liver and primary macrophages and hUCMSCs co-culture system in vitro to explore possible signaling pathways. PPAR\u03b3 antagonist, GW9662, and clodronate liposomes were used to inhibit PPAR activation and pre-exhaustion of macrophages in DLC rats\u2019 livers, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that changing the two key issues, the frequency and initial phase of hUCMSCs infusion, can affect the efficacy of hUCMSCs, and the optimal hUCMSCs treatment schedule is once every week for three weeks at the early stage of DLC progression, providing the best therapeutic effect in reducing mortality and ascites, and improving liver function in DLC rats. hUCMSCs treatment skewed the macrophage phenotype from M1-type to M2-type by activating the PPAR\u03b3 signaling pathway in the liver, which was approved by primary macrophages and hUCMSCs co-culture system in vitro. Both inhibition of PPAR\u03b3 activation with GW9662 and pre-exhaustion of macrophages in DLC rats\u2019 liver abolished the regulation of hUCMSCs on macrophage polarization, thus attenuating the beneficial effect of hUCMSCs treatment in DLC rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data demonstrated that the optimal hUCMSCs treatment effectively inhibits the ascites formation, prolongs survival and significantly improves liver structure and function in DLC rats through the activation of the PPAR\u03b3 signaling pathway within liver macrophages. Our study compared the efficacy of different hUCMSCs infusion regimens for DLC, providing new insights on cell-based therapies for regenerative medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-023-03416-2","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T08:02:28Z","timestamp":1690444948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["PPAR\u03b3-dependent hepatic macrophage switching acts as a central hub for hUCMSC-mediated alleviation of decompensated liver cirrhosis in rats"],"prefix":"10.1186","volume":"14","author":[{"given":"Yunqi","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushuang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8875-4493","authenticated-orcid":false,"given":"Hongxin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"issue":"10073","key":"3416_CR1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/S0140-6736(17)30187-3","volume":"389","author":"M Shiels","year":"2017","unstructured":"Shiels M, Chernyavskiy P, Anderson W, Best A, Haozous E, Hartge P, Rosenberg P, Thomas D, Freedman N, Berrington de Gonzalez A. 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Our study adheres to the Declaration of Helsinki. (1) Title of the approved project: Preclinical study of mesenchymal stem cells. Full name of the institutional approval committee or unit: Medical Ethics Committee of Sichuan University, Chengdu, China. Approval number: No. K2018109-1. Date of approval: 14.12. 2018. The reporting of this study conforms to ARRIVE guidelines. All experimental animals were well cared for and were raised and handled strictly in accordance with the \"Regulations on the Breeding and Management of Medical Experimental Animals in Sichuan Province\" and the \"Regulations on Experimental Animal Management of Sichuan University\". (2) Title of the approved project: Preclinical study of mesenchymal stem cells. Full name of the institutional approval committee or unit: Medical Ethics Committee of Sichuan University, Chengdu, China. Approval number: No. K2018109-2. Date of approval: 24.12.2018.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"184"}}