Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 192, Issue -, Pages 61-69Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2015.05.020
Keywords
Induced pluripotent stem cells; Exosomes/microvesicles; Myocardial ischemia/reperfusion; Apoptosis
Categories
Funding
- American Heart Association [0765094Y]
- NIH [HL086555, HL076684, HL62984]
- National Natural Science Foundation of China [81270203]
- Science and Technology Commission of Shanghai municipality [12ZR1432600]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL076684, R01HL124251, P01HL062984, R01HL112640, R01HL086555] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Background/objectives: Induced pluripotent stem cells (iPS) exhibit enhanced survival and proliferation in ischemic tissues. 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/microvesicles. Methods: Exosomes/microvesicles secreted from mouse cardiac fibroblast (CF)-derived iPS cells (iPS-exo) were purified from conditioned medium and confirmed by electron micrograph, size distribution and zeta potential by particle tracking analyzer and protein expression of the exosome markers CD63 and Tsg101. Results: We observed that exosomes are at low zeta potential, and easily aggregate. Temperature affects zeta potential (-14 to -15 mV at 23 degrees C vs -24 mV at 37 degrees C). The uptake of iPS-exo protects H9C2 cells against H2O2-induced oxidative stress by inhibiting caspase 3/7 activation (P < 0.05, n = 6). Importantly, iPS-exo treatment can protect against myocardial ischemia/reperfusion (MIR) injury via intramyocardial injection into mouse ischemic myocardium before reperfusion. Furthermore, iPS-exo deliver cardioprotective miRNAs, including nanogregulated miR-21 and HIF-1 alpha-regulated miR-210, to H9C2 cardiomyocytes in vitro. Conclusions: Exosomes/microvesicles secreted by iPS cells are very effective at transmitting cytoprotective signals to cardiomyocytes in the setting of MIR. iPS-exo thus represents novel biological nanoparticles that offer the benefits of iPS cell therapy without the risk of tumorigenicity and can potentially serve as an off-the-shelf therapy to rescue ischemic cardiomyocytes in conditions such as MIR. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available