Characterizing lung resident mesenchymal stem cells in idiopathic pulmonary fibrosis patients

Abstract

Introduction: Mesenchymal stem cells (MSCs) are multipotent cells with an impressive potential for regeneration and immunomodulation. The niche of resident MSCs in the lung is believed to play an important role in pulmonary disease; however, most of the studies are focused on MSC from other origin as bone marrow. Here, we performed a comprehensive study of the characteristics of lung MSCs in both donor and in idiopathic pulmonary fibrosis (IPF) patients. Results and methods: MSCs were isolated from donor and IPF human lung tissue and mesenchymality was confirmed by flow cytometry (Stemflow hMSC Analysis) and Rohart MSC in silico test. The differentiation capacity was assessed using the Human MSC Functional Identification kit and both conditions were able to differentiate into osteoblasts and adipocytes after 21 days, although less potential was observed in IPF lung MSCs for the last one. Moreover, functional analyses were performed for migration and proliferation by real-time monitoring cell assay. Notably, profibrotic stimulation by TGF-s induced a significant change by increasing migration and decreasing proliferation in the IPF-lung MSCs when compared to donor. Furthermore, the regenerative ability to close an epithelial wound was significantly reduced in lung MSCs from IPF patients as tested by scratch assay in indirect and direct co-culture. Conclusions: Lung MSCs were successfully isolated from both donor and IPF and could differentiate into other cell types. However, IPF lung MSCs displayed a decreased proliferation and an increased migration profile in response to fibrotic stimulus possibly due to an increased sensibility to profibrotic factors. Moreover, IPF lung MSCs had reduced regenerative potential which might be involved in the impaired repair in IPF pathogenesis.