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Can J Cardiol. 2014 Nov;30(11):1335-49. doi: 10.1016/j.cjca.2014.08.005. Epub 2014 Aug 15.

Transforming the promise of pluripotent stem cell-derived cardiomyocytes to a therapy: challenges and solutions for clinical trials.

Author information

1
Centre for Commercialization of Regenerative Medicine, Toronto, Ontario, Canada.
2
Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre at the University Health Network, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Waterloo, Ontario, Canada; Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; University Health Network, Toronto, Ontario, Canada; Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, Ontario, Canada.
3
Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre at the University Health Network, Toronto, Ontario, Canada; Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; University Health Network, Toronto, Ontario, Canada; Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, Ontario, Canada; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
4
Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre at the University Health Network, Toronto, Ontario, Canada; Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; University Health Network, Toronto, Ontario, Canada; Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, Ontario, Canada; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.
5
University Health Network, Toronto, Ontario, Canada; McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
6
Centre for Commercialization of Regenerative Medicine, Toronto, Ontario, Canada; Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.

Abstract

Despite advances in coronary artery disease treatment and prevention, myocardial damage due to acute myocardial infarction (MI) remains a major cause of morbidity and mortality in the population. Cell-based clinical trials to treat MI have focused on cells derived from the bone marrow or those potentially possessing functional similarities such as skeletal myoblasts or cardiac progenitors isolated from heart biopsies. Any benefits provided by these cells in improving heart function, left ventricular ejection fraction, or extending life expectancy after MI have been credited mostly to paracrine effects. Functional restoration of damaged myocardium will require a functional cell type with similar phenotype and characteristics of the damaged tissue that can also integrate, survive, and electrically couple to the host. Human pluripotent stem cells (hPSCs) have the ability to differentiate into multiple cell types of the adult body. hPSC-derived cardiomyocytes represent a promising target population for cell-based therapies for MI because they are scalable and the product can be defined with a specific set of release criteria. The purpose of this article is to review the rationale for cell therapy in heart disease, discuss the properties of hPSC cardiomyocytes that define their usefulness for regenerative therapy, consider manufacturing issues and preclinical investigation, and finally examine the steps required to establish effective clinical implementation. Pluripotent stem cell-derived cardiomyocyte-based therapies have enormous potential to revolutionize the management of heart disease; expedient but careful development is needed to ensure that this potential is fully realized.

PMID:
25442434
DOI:
10.1016/j.cjca.2014.08.005
[Indexed for MEDLINE]

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