EphA2-positive human umbilical cord-derived mesenchymal stem cells exert anti-fibrosis and immunomodulatory activities via secretion of prostaglandin E2

Abstract

Objective: Previous study has demonstrated that EphA2 is a biomarker of mesenchymal stem cells (MSCs) from human placenta or umbilical cord and is able to distinguish MSCs from fibroblasts. In this study, we further examine the potential efficacy of EphA2+ human umbilical cord-derived MSCs (hUC-MSCs). Materials and methods: MSCs specific markers, EphA2 and CD146 expression on the surface of hUC-MSCs were determined by flow cytometry analysis. Quantitative real time polymerase chain reaction was used to examine pro-fibrotic gene expression of TGF-β1-stimulated lung fibroblast (MRC-5 cells). On the other hand, ELISA was used to analyze the content of pro-inflammatory cytokines (TNF-ɑ; and IP-10) in the LPS-activated macrophages culture supernatant. Results: The pro-fibrotic gene (TGF-β1, CTGF, fibronectin, collagen I and TIMP-1) expression in TGF-β1-activated MRC-5 cells and the pro-inflammatory cytokines (TNF-ɑ and IP-10) in the LPS-activated macrophages culture supernatant were both attenuated when in present of EphA2+ hUC-MSCs. Moreover, once EphA2+ hUC-MSCs treated with prostaglandin E2 specific inhibitor NS-398, both anti-fibrotic and anti-inflammatory effects of EphA2+ hUC-MSCs were abolished. Conclusion: EphA2+ hUC-MSCs possess immunomodulatory and anti-fibrotic properties, and PGE2 plays an important role in these activities. This implies that EphA2+ hUC-MSCs have potentially effectiveness for treatment of acute inflammatory and chronic fibrotic lung diseases. Keywords: Anti-fibrosis, EphA2, Immunomodulatory, Mesenchymal stem cells, Prostaglandin E2