Long-Term Improvement in Post-Infarct Left Ventricular Global and Regional Contractile Function Mediated by Embryonic Stem Cell-Derived Cardiomyocytes.
Circ Cardiovasc Imaging. 2010 Nov 8;
Authors: Qiao H, Zhang H, Yamanaka S, Patel VV, Petrenko NB, Huang B, Muenz LR, Ferrari VA, Boheler KR, Zhou R
BACKGROUND: -Pluripotent stem cells represent one promising source for cellular cardiomyoplasty. In this study, we employed cardiac magnetic resonance (CMR) to examine the ability of highly enriched cardiomyocytes (CMs) derived from murine embryonic stem cells (ESC) to form grafts and improve contractile function of infarcted rat hearts. METHODS AND RESULTS: -Highly enriched ESC-CMs were obtained by inducing cardiac differentiation of ESCs stably expressing a cardiac restricted puromycin resistance gene. At the time of transplantation, enriched ESC-CMs expressed cardiac specific markers and markers of developing CMs but only 6% of them were proliferating. A growth factor containing vehicle solution or ESC-CMs (5-10 million) suspended in the same solution was injected into athymic rat hearts one week after myocardial infarction (MI). Initial infarct size was measured by CMR one day post-MI. Compared to vehicle, treatment with ESC-CMs improved global systolic function at 1 and 2-months post injection, and significantly increased contractile function in initially infarcted and border zones. Immunohistochemistry confirmed successful engraftment and the persistence of ?-actinin positive ESC-CMs that also expressed ?-smooth muscle actin. Connexin-43 positive sites were observed between grafted ESC-CMs but only rarely between grafted and host CMs. No teratomas were observed in any of the animals. CONCLUSIONS: -Highly enriched and early staged ESC-CMs were safe, formed stable grafts and mediated a long-term recovery of global and regional myocardial contractile function following infarction.
PMID: 21059858 [PubMed - as supplied by publisher]