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-1α 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-1α and then evaluated their viability following exposure to hypoxic and oxidative stresses. The inherent expression of HIF-1α 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-1α 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.
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-1α 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-1α and then evaluated their viability following exposure to hypoxic and oxidative stresses. The inherent expression of HIF-1α 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-1α 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.
Authors: Anna P Hnatiuk; Sang-Ging Ong; Fernanda D Olea; Paola Locatelli; Johannes Riegler; Won Hee Lee; Cheng Hao Jen; Andrea De Lorenzi; Carlos S Giménez; Rubén Laguens; Joseph C Wu; Alberto Crottogini Journal: J Am Heart Assoc Date: 2016-07-06 Impact factor: 5.501