Effect of CoCl2 or H2O2 pre-conditioned mesenchymal stem cells in a mouse model of pulmonary fibrosis

Abstract

Introduction: Pulmonary Fibrosis is characterized by excessive matrix deposition which leads to airway remodeling and disruption of the typical architecture of the lung parenchyma. The disease progression is associated with a high mortality rate. The current treatment for pulmonary fibrosis includes drugs which either reduce progression of the disease or provide symptomatic relief. Multiple studies have examined the effect of cell-based therapy in pulmonary fibrosis. We investigated the effect of administration of pre-conditioned bone marrow-derived mesenchymal stem cells (BM-MSC) in a mouse model of pulmonary fibrosis.

Methods: Firstly, we examined the effect of pre-conditioning on the cells using cell-based assays. We found that pre-conditioning did not significantly alter cell proliferation or led to cellular inflammation. The cells continued to express MSC marker, CD105, and pluripotency marker Oct3/4. Next, we evaluated the proliferative and anti-inflammatory potential of BM-MSC administration using a series of assays in a mouse model of pulmonary fibrosis. Bleomycin was administered to induce pulmonary fibrosis in mice on Day 0. MSCs were administered on day 1 and day 3; the mice were sacrificed on day 22, and their tissues were collected for analysis.

Results: We found that similar to untreated cells, administration of pre-conditioned cells resulted in an increase in the proliferative potential and reduction in inflammation in the lung tissue, bronchoalveolar lavage, bone marrow, and blood. We observed reduction in the number of granulocytes in peripheral blood upon MSC administration. However, we did not observe any structural changes in the lung upon MSC administration. We found a small reduction in collagen content in the lung which was also seen upon staining with Masson's trichrome.

Conclusion: These results demonstrate that pre-conditioned BM-MSC lead to improvement in the disease state through paracrine effects but pre-conditioning of cells for 24 hours does not significantly improve the beneficial effect of MSC administration.