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

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 simulta...

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Bibliographic Details
Published in:Journal of cellular physiology 2018-08, Vol.233 (8), p.5503-5512
Main Authors: Rubio, Gustavo A., Elliot, Sharon J., Wikramanayake, Tongyu C., Xia, Xiaomei, Pereira‐Simon, Simone, Thaller, Seth R., Glinos, George D., Jozic, Ivan, Hirt, Penelope, Pastar, Irena, Tomic‐Canic, Marjana, Glassberg, Marilyn K.
Format: Article
Language:English
Subjects:
AKT protein
Animals
Bleomycin
Bleomycin - pharmacology
Caveolin
Caveolin 1 - metabolism
Disease Models, Animal
Fibrosis
Injury prevention
Kinases
Lung - cytology
Lung - drug effects
Lung - metabolism
Lungs
Male
Medical treatment
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal stem cells
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Mesenchyme
Mice
Mice, Inbred C57BL
MicroRNAs - metabolism
MSC
Organs
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
Pulmonary Fibrosis - chemically induced
Pulmonary Fibrosis - metabolism
Pulmonary Fibrosis - prevention & control
Rodents
Skin
Skin - cytology
Skin - drug effects
Skin - metabolism
Skin Diseases - chemically induced
Skin Diseases - metabolism
Skin Diseases - prevention & control
Stromal cells
Trachea
Wound healing
Wound Healing - drug effects
Wound Healing - physiology
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Summary: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. We utilized an established aged mouse model of bleomycin‐induced lung fibrosis to test if fibrosis may develop simultaneously in multiple organs by evaluating skin fibrosis and wound healing. We found that 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, mice treated with systemic injection of allogeneic adipose‐derived mesenchymal stromal cells (ASCs) 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.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.26418