Comparison of Human Embryonic Stem Cell-Derived Cardiomyocytes, Cardiovascular Progenitors, and Bone Marrow Mononuclear Cells for Cardiac Repair

Sarah Fernandes; James J H Chong; Sharon L Paige; Mineo Iwata; Beverly Torok-Storb; Gordon Keller; Hans Reinecke; Charles E Murry

doi:10.1016/j.stemcr.2015.09.011

Comparison of Human Embryonic Stem Cell-Derived Cardiomyocytes, Cardiovascular Progenitors, and Bone Marrow Mononuclear Cells for Cardiac Repair

Stem Cell Reports. 2015 Nov 10;5(5):753-762. doi: 10.1016/j.stemcr.2015.09.011.

Authors

Sarah Fernandes¹, James J H Chong², Sharon L Paige¹, Mineo Iwata³, Beverly Torok-Storb³, Gordon Keller⁴, Hans Reinecke¹, Charles E Murry⁵

Affiliations

¹ Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Department of Pathology, University of Washington, Seattle, WA 98109, USA.
² Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Department of Pathology, University of Washington, Seattle, WA 98109, USA; School of Medicine, University of Sydney, Sydney, NSW 2006, Australia; Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, NSW 2145, Australia.
³ Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁴ McEwen Centre for Regenerative Medicine, Ontario Cancer Institute, Toronto, ON M5G 2M9, Canada.
⁵ Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Department of Pathology, University of Washington, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA 98109, USA. Electronic address: [email protected].

Abstract

Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) can improve the contractility of injured hearts.We hypothesized that mesodermal cardiovascular progenitors (hESC-CVPs), capable of generating vascular cells in addition to cardiomyocytes, would provide superior repair by contributing to multiple components of myocardium. We performed a head-to-head comparison of hESC-CMs and hESC-CVPs and compared these with the most commonly used clinical cell type, human bone marrow mononuclear cells (hBMMNCs). In a nude rat model of myocardial infarction, hESC-CMs and hESC-CVPs generated comparable grafts. Both similarly improved systolic function and ventricular dilation. Furthermore, only rare human vessels formed from hESC-CVPs. hBM-MNCs attenuated ventricular dilation and enhanced host vascularization without engrafting long-term or improving contractility. Thus, hESC-CMs and CVPs show similar efficacy for cardiac repair, and both are more efficient than hBM-MNCs. However, hESC-CVPs do not form larger grafts or more significant numbers of human vessels in the infarcted heart.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Embryonic Stem Cells / cytology*
Endothelial Progenitor Cells / cytology*
Humans
Male
Myocardial Contraction
Myocardial Infarction / therapy*
Myocytes, Cardiac / cytology*
Myocytes, Cardiac / physiology
Rats
Rats, Sprague-Dawley
Stem Cell Transplantation*
Ventricular Function

Abstract

Publication types

MeSH terms

Grants and funding