Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction
By Mohsin Khan, Emily Nickoloff, T. Abramova, Jennifer M. Johnson, S. Verma, P. Krishnamurthy, A. Mackie, E. Vaughan, V. Garikipati, Cindy Benedict and 11 more. Circulation Research, 2015
641 citations recorded by the source corpus.
Rationale Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome secretion. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective Determine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit+ CPCs function can be enhanced with ESC exosomes Methods and Results This study demonstrates that mouse ESC derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290–295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression and proliferation. Conclusions mES Ex provide a novel cell free system that utilizes the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC based repair programs in the heart.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/17f1ced24593487ea01a02424b6e89e87fdcae62
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Citations in the corpus
- Clinical applications of stem cell-derived exosomes (2024, background): “276 In addition, Tavakoli Dargagni et al. demonstrated that ESC-derived exosomes could alleviate doxorubicin-induced cardiotoxicity by inhibiting TLR4-NLRP3-mediated pyroptotic cell death in cardiomyocytes.”
- Exosome Theranostics: Biology and Translational Medicine (2018, background): “Many studies have demonstrated that exosomes can play significant roles in the treatment of many diseases, including cancer [137], cardiovascular diseases [138, 139], neurodegenerative diseases [61], tissue injury [140], and pathogenic infections [141].”
- Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease (2019, background): “The latter appears to be mediated in part by miR-294 and is accompanied by increased cardiac neovascularization, improved cardiac function, and increased cardiac stem cell proliferation (Khan et al., 2015).”