Physical and Genetic Preconditioning of Adipose-Derived Stem Cells to Survive Ischemia

The survival rate of stem cells following implantation can determine the regenerative potential of stem cells. After cells are exposed to the severe stress environment of injured tissues which are beyond their cyto-protective capacity, the majority of stem cells undergo apoptosis within one week. According to numerous prior studies, the post-stress damage of cells can be abrogated by inducing an elevated level of stress proteins (e.g. heat shock protein). However, the detailed interaction between stress proteins and stem cell activities are not well-described. In the current study, we seek to develop a robust stem cell source with strong apoptotic resistance for tissue engineering applications. We are interested in whether or not up-regulation of stress proteins, as a result of stem cell preconditioning, can improve the survival and subsequent regenerative potential of stem cells. We successfully up-regulated heat shock protein 70 (HSP70) in adipose-derived stem cells (ASCs) without significant cytotoxicity by either exogenous delivery of a HSP70 cDNA plasmid or physical stress treatment (e.g. mild heating or oxidative stress). Current studies are focused on comparing the effect of physical stresses and gene manipulation strategies on the behaviors (viability growth, protein production, morphology) of HSP70-upregulated ASCs under an in vitro ischemic environment. The result of this work will identify an effective stem cell preconditioning protocol to produce a stem cell source more resistant to severe stress environments.