Development of Novel Strategies to Synergistically Improves Cardiac Function and Vascular Regeneration Following Myocardial Infarction

發展新對策以協同性改善心肌梗塞後的心臟功能和血管再生

Student thesis: Doctoral Thesis

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Award date17 Aug 2020

Abstract

Cardiovascular disease including myocardial infarction (MI) is one of the major causes of death worldwide despite advances in biomedical sciences. Since both myocardium and vasculature in the heart are excessively damaged following MI, therapeutic strategies for heart regeneration should simultaneously target both of them to accomplish an actual cardiac repair. Here, we report two concomitant strategies that restore myocardium and vasculatures simultaneously through 1) a combination of transcription factors, ETV2 and Gata4/Mef2c/Tbx5 (GMT) and 2) two distinct types of stem cells including cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cells derived from human bone marrow. Both strategies were examined on a rat MI model and, as results, we found that both therapeutic approaches lead significant improvement of cardiac functions and as well as capillary density indicating achievement of comprehensive cardiac repair via increase of the survival of myocardium and promotion of vessel regeneration. Together, our results demonstrate that these novel approaches aiming to simultaneously salvage both myocardium and vasculatures possess significant therapeutic potential for cardiac regenerative therapy.