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Am J Physiol Lung Cell Mol Physiol. 2017 Apr 6:ajplung.00323.2016. doi: 10.1152/ajplung.00323.2016. [Epub ahead of print]

Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model.

Author information

1
University of Pittsburgh.
2
University of Pittsburgh school of Medicine.
3
Yale University.
4
University of Pittsburgh rojasm@upmc.edu.

Abstract

Although different preclinical models have demonstrated a favorable role for bone marrow derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (anti-fibrotic) or miR-154 (pro-fibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modified B-MSCs were intravenously administered to mice at day 7 after bleomycin instillation and the mice were sacrificed at day 14. Bleomycin-injured animals treated with let-7d cells were found to recover quicker from the initial weight loss compared to the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no significant differences were observed in Ashcroft score and OH-proline. However, the distinctive expression in cytokines and CD45 positive cells in the lung suggest that the differential effects observed in both miRNAs mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modified mesenchymal stem cells as a potential future research in lung fibrosis.

KEYWORDS:

Bone marrow derived mesenchymal stem cells; Lung fibrosis; miRNA

PMID:
28385811
DOI:
10.1152/ajplung.00323.2016
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