High Density Lipoprotein Protects Mesenchymal Stem Cells from Oxidative Stress-Induced Apoptosis via Activation of the PI3K/Akt Pathway and Suppression of Reactive Oxygen Species

Abstract

The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H2O2) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H2O2-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS.

Reactive Oxygen Species Regulate Hematopoietic Stem Cell Self-Renewal, Migration and Development, As Well As Their Bone Marrow Microenvironment

“…Human stromal cells express high basal levels of the ROS scavenger Gluthatione, which enables them to maintain low intracellular ROS levels on introducing high levels of ROS to their culture (108). In addition, high-density lipoprotein was shown to protect BM stromal cells from ROS-induced apoptosis by inhibiting ROS accumulation in them in an Akt/PI3K-dependent manner (116). However, accumulation of moderate levels of ROS is important for immature stromal cell differentiation.…”

Platelet Rich Plasma Clot Releasate Preconditioning Induced PI3K/AKT/NFκB Signaling Enhances Survival and Regenerative Function of Rat Bone Marrow Mesenchymal Stem Cells in Hostile Microenvironments

“…For instance, transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have been reported to often fail engraftment within the bone marrow (BM) partly due to the poor cell viability of donor cells. Additionally, the therapeutic effects of transplanted MSCs in myocardial infarction appear to be limited by the poor survival of donor cells in the injured myocardial tissue [10,11]. The underlying cause of the massive MSC death is multifactorial, and the prime factors responsible may be the loss of trophic factors, local tissue ischemia, production of reactive oxygen species after ischemic reperfusion injury, and host inflammatory response mediators [12][13][14].…”

miR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation

“…Because the c-Met pathway is a key mechanism associated with cell apoptosis [13], we focused on the change of c-Met phosphorylation during this process. Additionally, we examined the activity of superoxide dismutase (SOD) [14], the level of malonaldehyde (MDA) [15], and the accumulation of ROS [16], which are reliable indicators for cellular oxidative stress. Hydrogen peroxide (H 2 O 2 ), widely used as an oxidant in vitro, was applied to develop a cellular model of oxidative stress damage.…”