Oleoylethanolamide protects mesenchymal stem/stromal cells (MSCs) from oxidative stress and reduces adipogenic related genes expression in adipose-derived MSCs undergoing adipocyte differentiation.

Abstract

Human mesenchymal stem/stromal cells (hMSCs) are known for their pronounced therapeutic potential; however, they are still applied in limited clinical cases for several reasons. ROS-mediated oxidative stress is among the chief causes of post-transplantation apoptosis and death of hMSCs. It has been reported that a strategy to protect hMSCs against ROS is to pretreat them with antioxidants. Oleoylethanolamide (OEA) is a monounsaturated fatty acid derived from oleic acid and it has many protective properties, including anti-obesity, anti-inflammatory, and antioxidant effects. OEA is also used as a weight loss supplement; due to its high affinity for the PPAR-α receptor, OEA increases the fat metabolism rate. This study hence assessed the effects of OEA pretreatment on the in vitro survival rate and resistance of hMSCs under oxidative stress as well as the cellular and molecular events in the biology of stem/stromal cells affected by oxidative stress and free radicals. Considering the role of MSCs in adipogenesis and obesity, the expression of the main genes involved in adipogenesis was also addressed in this study. Results revealed that OEA increases the in vitro proliferation of MSCs and inhibits cell apoptosis by reducing the induction of oxidative stress. The results also indicated that OEA exerts its antioxidant properties by both activating the Nrf2/NQO-1/HO-1 signaling pathway and directly combating free radicals. Moreover, OEA can reduce adipogenesis through reducing the expression of PPARγ, leptin and CEBPA genes in hMSCs undergoing adipocyte differentiation. Thus, OEA protects hMSCs from oxidative stress and reduces adipogenic related genes expression and can be regarded as a therapeutic agent for this purpose.