Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium

Yingjie Wang, Lan Zhang, Yongjun Li, Lijuan Chen, Xiaolong Wang, Wei Guo, Xue Zhang, Gangjian Qin, Sheng Hu He, Arthur Zimmerman, Yutao Liu, Il Man Kim, Neal L. Weintraub, Yaoliang Tang

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159 Scopus citations

Abstract

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 °C vs - 24 mV at 37 °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 nanog-regulated miR-21 and HIF-1α-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.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalInternational Journal of Cardiology
Volume192
DOIs
StatePublished - Jun 9 2015

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Keywords

  • Apoptosis
  • Exosomes/microvesicles
  • Induced pluripotent stem cells
  • Myocardial ischemia/reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Wang, Y., Zhang, L., Li, Y., Chen, L., Wang, X., Guo, W., Zhang, X., Qin, G., He, S. H., Zimmerman, A., Liu, Y., Kim, I. M., Weintraub, N. L., & Tang, Y. (2015). Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. International Journal of Cardiology, 192, 61-69. https://doi.org/10.1016/j.ijcard.2015.05.020