@article{493d301afc5848ac9a74aa7b69048da4,
title = "Mesenchymal stromal cells prevent bleomycin-induced lung and skin fibrosis in aged mice and restore wound healing",
abstract = "Fibrosis can develop in nearly any tissue leading to a wide range of chronic fibrotic diseases. However, current treatment options are limited. In this study, we utilized an established aged mouse model of bleomycin-induced lung fibrosis (BLM) to test our hypothesis that fibrosis may develop simultaneously in multiple organs by evaluating skin fibrosis and wound healing. Fibrosis was induced in lung in aged (18–22-month-old) C57BL/6 male mice by intratracheal BLM administration. Allogeneic adipose-derived mesenchymal stromal cells (ASCs) or saline were injected intravenously 24 hr after BLM administration. Full thickness 8-mm punch wounds were performed 7 days later to study potential systemic anti-fibrotic and wound healing effects of intravenously delivered ASCs. Mice developed lung and skin fibrosis as well as delayed wound closure. Moreover, we observed similar changes in the expression of known pro-fibrotic factors in both lung and skin wound tissue, including miR-199 and protein expression of its corresponding target, caveolin-1, as well as phosphorylation of protein kinase B. Importantly, ASC-treated mice exhibited attenuation of BLM-induced lung and skin fibrosis and accelerated wound healing, suggesting that ASCs may prime injured tissues and prevent end-organ fibrosis.",
keywords = "MSC, fibrosis, wound healing",
author = "Rubio, {Gustavo A.} and Elliot, {Sharon J.} and Wikramanayake, {Tongyu C.} and Xiaomei Xia and Simone Pereira-Simon and Thaller, {Seth R.} and Glinos, {George D.} and Ivan Jozic and Penelope Hirt and Irena Pastar and Marjana Tomic-Canic and Glassberg, {Marilyn K.}",
note = "Funding Information: National Institute of Nursing Research, Grant numbers: NR013881, NR015649; The Lester and Sue Smith Foundation; The James S. Fauver Pulmonary Fibrosis Research Fund Funding Information: We are grateful to all members of our laboratories for helpful criticisms and overall support. This work was funded by NIH grants NR013881 and NR015649 (MT-C). The authors also thank the Lester and Sue Smith Foundation and the James S. Fauver Pulmonary Fibrosis Research Fund for their generous support in research funding. SJE, IP, SRT, MTC, SRT, and MKG conceived and designed the study. GAR, TW, XX, SPS, GDG, IJ, and PH performed experiments and data acquisition. GAR, SJE, TW, IP, MTC, and MKG performed data analysis and interpretation. GAR, SJE, SRT, IP, MTC, and MKG participated in manuscript writing and critical revisions. All authors read and approved final manuscript. Dr. Glassberg serves as a consultant expert on advisory boards for Genentech, Boehringer Ingelheim, Patara Pharma, and Bellerophon Therapeutics. All other authors have indicated no conflict of interest. Funding Information: We are grateful to all members of our laboratories for helpful criticisms and overall support. This work was funded by NIH grants NR013881 and NR015649 (MT-C). The authors also thank the Lester and Sue Smith Foundation and the James S. Fauver Pulmonary Fibrosis Research Fund for their generous support in research funding. Publisher Copyright: {\textcopyright} 2017 Wiley Periodicals, Inc.",
year = "2018",
month = aug,
doi = "10.1002/jcp.26418",
language = "English (US)",
volume = "233",
pages = "5503--5512",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "8",
}