A cross-disciplinary group of researchers at the University of Miami Miller School of Medicine has found that allogeneic adipose-derived mesenchymal stromal cells (ASCs) will prevent lung and skin fibrosis, and restore wound healing.
Fibrosis can develop in nearly any tissue, leading to a wide range of chronic fibrotic diseases. Current treatment options, however, are limited. In this NIH-funded study, researchers evaluated skin fibrosis and wound healing in an established aged mouse model of bleomycin-induced lung fibrosis (BLM) to test their hypothesis that fibrosis may develop simultaneously in multiple organs.
Fibrosis was induced in the lungs of aged (18-22 month-old) C57BL/6 male mice by intratracheal BLM administration. ASCs or saline were injected intravenously 24 hours after BLM administration. Full thickness 8-mm punch wounds were performed seven days later to study potential systemic anti-fibrotic and wound healing effects of intravenously delivered ASCs.
“The mice developed lung and skin fibrosis, as well as delayed wound closure,” said Marjana Tomic-Canic, Ph.D., professor of dermatology, vice chair of research, and director of the Wound Healing and Regenerative Medicine Research Program in the Department of Dermatology and Cutaneous Surgery, who was one of the researchers in the study. “Moreover, we observed similar changes in the expression of known pro-fibrotic factors in both lung and skin wound tissue, including microRNA-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.”
The research findings were reported in an article, “Mesenchymal stromal cells prevent bleomycin-induced lung and skin fibrosis in aged mice and restore wound healing,” published online by the Journal of Cell Physiology, with Tomic-Canic as one of the corresponding authors. Additional Miller School co-investigators from the Department of Dermatology and Cutaneous Surgery were Tongyu Cao Wikramanyake, Ph.D., research assistant professor, and Irena Pastar, Ph.D., research assistant professor. Additional members of the research team were Seth R. Thaller, M.D., D.M.D., professor of surgery, Sharon J. Elliot, Ph.D., research professor of surgery, and Marilyn K. Glassberg, M.D., professor of medicine and surgery, director of the Interstitial Lung Disease Program and director of pulmonary diseases at the Interdisciplinary Stem Cell Institute.
“This study resulted from collaborative efforts of multiple laboratories across different departments and represent a true multi-disciplinary research effort,” said Tomic-Canic. “To our knowledge, this is the first report of a systemic mechanism of ASC action on dual-organ fibrosis in vivo in an aged murine bleomycin model.”
The next step, she says, will be expanding research to studies using ASCs as a systemic anti-fibrotic therapy, affecting the pathophysiology of multiple organs simultaneously.