{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:04:16Z","timestamp":1793163856016,"version":"4.5.0"},"reference-count":96,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Defense (DOD)","award":["W81XWH-19-1-0129"],"award-info":[{"award-number":["W81XWH-19-1-0129"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibroblast-to-myofibroblast transition (FMT) leads to excessive extracellular matrix (ECM) deposition\u2014a well-known hallmark of fibrotic disease. Transforming growth factor-\u03b2 (TGF-\u03b2) is the primary cytokine driving FMT, and this phenotypic conversion is associated with mitochondrial dysfunction, notably a metabolic reprogramming towards enhanced glycolysis. The objective of this study was to examine whether the establishment of favorable metabolic phenotypes in TGF-\u03b2-stimulated fibroblasts could attenuate FMT. The hypothesis was that mitochondrial replenishment of TGF-\u03b2-stimulated fibroblasts would counteract a shift towards glycolytic metabolism, consequently offsetting pro-fibrotic processes. Isolated mitochondria, functionalized with a dextran and triphenylphosphonium (TPP) (Dex-TPP) polymer conjugate, were administered to fibroblasts (MRC-5 cells) stimulated with TGF-\u03b2, and effects on bioenergetics and fibrotic programming were subsequently examined. Results demonstrate that TGF-\u03b2 stimulation of fibroblasts led to FMT, which was associated with enhanced glycolysis. Dex-TPP-coated mitochondria (Dex-TPP\/Mt) delivery to TGF-\u03b2-stimulated fibroblasts abrogated a metabolic shift towards glycolysis and led to a reduction in reactive oxygen species (ROS) generation. Importantly, TGF-\u03b2-stimulated fibroblasts treated with Dex-TPP\/Mt had lessened expression of FMT markers and ECM proteins, as well as reduced migration and proliferation. Findings highlight the potential of mitochondrial transfer, as well as other strategies involving functional reinforcement of mitochondria, as viable therapeutic modalities in fibrosis.<\/jats:p>","DOI":"10.3390\/ijms241310913","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:06:37Z","timestamp":1688141197000},"page":"10913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Polymer-Functionalized Mitochondrial Transplantation to Fibroblasts Counteracts a Pro-Fibrotic Phenotype"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5231-7045","authenticated-orcid":false,"given":"Gherardo","family":"Baudo","sequence":"first","affiliation":[{"name":"Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"College of Materials Sciences and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"College of Materials Sciences and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2826-5433","authenticated-orcid":false,"given":"Hyunho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1491-8528","authenticated-orcid":false,"given":"Aijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Bioenergetics, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-2746","authenticated-orcid":false,"given":"Dale J.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Center for Bioenergetics, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA"},{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvin","family":"Blanco","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA"},{"name":"Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","article-title":"Fibrosis: From mechanisms to medicines","volume":"587","author":"Henderson","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17074","DOI":"10.1038\/nrdp.2017.74","article-title":"Idiopathic pulmonary fibrosis","volume":"3","author":"Martinez","year":"2017","journal-title":"Nat. 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