Treatment with hESC-derived myocardial precursors improves cardiac function after a myocardial infarction

Jianqin Ye, Meenakshi Gaur, Yan Zhang, Richard E. Sievers, Brandon J. Woods, Julian Aurigui, Harold S. Bernstein, Yerem Yeghiazarians

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: We previously reported the generation of a reporter line of human embryonic stem cells (hESCs) with enhanced green fluorescent protein (eGFP) expression driven by the α-myosin heavy chain (αMHC) promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI). Methods: MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs) were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining. Results: Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI. Conclusion: Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.

Original languageEnglish
Article numbere0131123
JournalPLoS ONE
Volume10
Issue number7
DOIs
StatePublished - 31 Jul 2015
Externally publishedYes

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