HIF-1α Confers Resistance to Induced Stress in Bone Marrow-derived Mesenchymal Stem Cells

Background and Aims. The major limiting factor in therapeutic application of mesenchymal stem cells (MSCs) is their high vulnerability during the early days of transplantation. Hence, researchers have been encouraged to find various strategies to make the cells resistant to different stresses before and after transplantation. Overexpression of HIF-1 alpha in MSCs to confer resistance against harmful conditions was the aim of this study. Methods. Using an in vitro approach, we engineered MSCs to overexpress HIF-1 alpha and then evaluated their viability following exposure to hypoxic and oxidative stresses. The inherent expression of HIF-1 alpha was downregulated by siRNA. Viability and apoptosis of the MSCs were then evaluated in vitro following their exposure to hypoxic and oxidative stress conditions. Results. Whereas overexpression of HIF-1 alpha in MSCs was protective against cell death and apoptosis triggered by hypoxic and oxidative stress conditions, its downregulation increased apoptosis and death rate. Conclusions. Our study is the first to demonstrate how human MSCs can be manipulated to gain protection against stresses that potentially limit their clinical application. (C) 2013 IMSS. Published by Elsevier Inc.