Author + information
Stem cell (SC) therapy for the ischemic cardiomyopathy is hampered due to poor survival of implanted cells. Recently, SC-derived exosomes have been identified to facilitate cell proliferation and survival by transporting various proteins and noncoding RNAs (such as microRNAs and lncRNAs).This study aimed to evaluate the effect of miR-21 derived exosomes produced by H2O2 pretreatment MSC（H2O2-Exo）on H2O2-mediated c-kitposCSCs cell injury.
We hypothesized that exosomal miR-21 derived from H2O2-treated MSCs could be transported to C-kit+ CSC in which functionally inhibits the PTEN expression and thereby, activates the PI3K/AKT signal, leading to protection against oxidative stress-triggered cell death.
In this study, we observed that miR-21 was highly enriched in exosomes collected from hydrogen peroxide (H2O2)-treated MSCs (H-Exo) than those exosomes released from MSCs under normal conditions (N-Exo). Pre-treatment of C-kit+ cardiac stem cells (CSCs) with H-Exo resulted in significant increased levels of miR-21 and phosphor-Akt (pAkt), whereas decreased levels of PTEN, a bona fide target of miR-21(figure). AnnexinV-FITC/PI analysis further demonstrated that the degree of oxidative stress-induced apoptosis were greatly reduced in H-Exo-treated C-kit+CSCs, compared to N-Exo-treated cells. Such protective effects could be blocked by both miR-21 inhibitor and PI3K/Akt inhibitor LY294002.
Thus, exosomes derived from MSCs could be used as a new therapeutic vehicle to facilitate the C-kit+ CSC therapy in ischemic myocardium.
CORONARY: Cell Therapy and Angiogenesis