Department of Hematology and Blood Banking, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Arch Med Res. 2013 Apr;44(3):185-93. doi: 10.1016/j.arcmed.2013.03.006. Epub 2013 Mar 21.
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.
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.
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.
Our study is the first to demonstrate how human MSCs can be manipulated to gain protection against stresses that potentially limit their clinical application.
间充质干细胞（MSCs）在治疗应用中的主要限制因素是其在移植早期的高度脆弱性。因此，研究人员一直在寻找各种策略，以使细胞在移植前后能够抵抗不同的应激。本研究旨在通过过表达 HIF-1α 使 MSCs 具有抵抗有害条件的能力。
我们采用体外方法使 MSCs 过表达 HIF-1α，然后评估其在暴露于低氧和氧化应激后存活情况。通过 siRNA 下调 HIF-1α 的内源性表达。然后，在体外暴露于低氧和氧化应激条件下，评估 MSCs 的存活和凋亡情况。
过表达 HIF-1α 可保护 MSCs 免受低氧和氧化应激条件引发的细胞死亡和凋亡，而其下调则增加了凋亡和死亡率。
我们的研究首次证明了如何操纵人 MSCs 以获得对潜在限制其临床应用的应激的保护。
