Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium
| Autor: | Yongjun Li, Xiaolong Wang, Arthur D. Zimmerman, Yutao Liu, Gangjian Qin, Yingjie Wang, Neal L. Weintraub, Lan Zhang, Yao Liang Tang, Sheng Hu He, Il-man Kim, Lijuan Chen, Xue Zhang, Wei Guo |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Induced Pluripotent Stem Cells
Myocardial Ischemia Caspase 3 Apoptosis Myocardial Reperfusion Injury Exosomes Exosome Article Mice Cell-Derived Microparticles microRNA Medicine TSG101 Animals Myocytes Cardiac Induced pluripotent stem cell Cells Cultured CD63 business.industry Fibroblasts Microvesicles Cell biology MicroRNAs Immunology Cardiology and Cardiovascular Medicine business |
| Popis: | 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.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.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 (P0.05, 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.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. |
| Databáze: | OpenAIRE |
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