Abstract 17048: Exosomes From Induced Pluripotent Stem Cells Deliver Cardioprotective Mirnas and Prevent Cardiomyocyte Apoptosis in the Ischemic Myocardium
Induced pluripotent stem (iPS) cells exhibit enhanced survival and proliferation in ischemic myocardium and thus represent a promising source of cell-based therapy for myocardial ischemia-reperfusion (MIR) injury. However, the therapeutic application of iPS cells is limited by their tumorigenic potential. We hypothesized that iPS cells can transmit cytoprotective signals to cardiomyocytes via exosomes, nanovesicles that contain proteins, mRNAs and microRNAs (miRNAs) that can regulate cell function. Exosomes secreted from mouse cardiac fibroblast (CF)-derived iPS cells (iPS-exo) were purified from conditioned medium and confirmed by electron micrograph and protein expression of the exosome markers CD63 and Tsg101. We observed that iPS-exo are taken up by cultured H9C2 cardiomyocytes with high efficiency in time-dependent fashion. Uptake of iPS-exo protects H9C2 cells against H2O2-induced oxidative stress by inhibiting caspase 3/7 activation (P<0.05, n=6). To investigate whether iPS-exo treatment can protect against MIR injury, we injected exosomes secreted by CF (CF-exo), iPS-exo, or PBS (control) intramyocardially into mouse ischemic myocardium before reperfusion. After 24hs, TUNEL analysis showed that iPS-exo reduced cardiomyocyte apoptosis by about 66% in comparison with PBS control (p<0.05, n=6), and by about 50% in comparison with CF-iPS (P<0.05, n=6). Western blotting demonstrated that iPS-exo treatment significantly decreased the active caspase3 compared with PBS and CF-exo treatment (P<0.05, n=3). Furthermore, iPS-exo deliver cardioprotective miRNAs, including Nanog-regulated miR-21 and HIF-1α-regulated miR-210, to H9C2 cardiomyocytes in vitro. In conclusion, iPS-exo are biological nanoparticles carrying survival messages that can be efficiently transmitted to cardiomyocytes to protect against MIR.
Author Disclosures: Y. Wang: None. L. Zhang: None. N.L. Weintraub: None. Y. Tang: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.