Mesenchymal stromal cells prevent bleomycin-induced lung and skin fibrosis in aged mice and restore wound healing

Gustavo A. Rubio, Sharon J. Elliot, Tongyu C. Wikramanayake, Xiaomei Xia, Simone Pereira-Simon, Seth R. Thaller, George D. Glinos, Ivan Jozic, Penelope Hirt, Irena Pastar, Marjana Tomic-Canic, Marilyn K. Glassberg

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5503-5512
Number of pages10
JournalJournal of Cellular Physiology
Volume233
Issue number8
DOIs
StatePublished - Aug 2018

Keywords

  • MSC
  • fibrosis
  • wound healing

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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