Cell-based therapy for myocardial ischemia and infarction: pathophysiological mechanisms.
Cell-based cardiac repair has emerged as an attractive approach to preventing or reversing heart failure resulting from myocyte dysfunction-e.g., due to infarction-and to enhancing the development of collaterals in patients with symptoms of myocardial ischemia. These two problems involve both overlapping and differing mechanisms, and these differences must be considered in cell-based therapies. In terms of myocardial dysfunction due to infarction, only committed cardiomyocytes have been shown to form new myocardium that is electrically coupled with the host heart. Despite this, multiple cell populations appear to improve function of the infarcted heart, including many that are clearly nonmyogenic. In terms of myocardial ischemia, although cell-based strategies improve ischemia in animal models, clinical trials to date have not shown robustly beneficial results. We review the evidence for potential mechanisms underlying the benefits of cell transplantation in the heart and discuss the clinical contexts in which they may be relevant.
Department of Pathology, Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA. laflamme@u.washington.edu
Michael A
MA
Laflamme
Stephan
S
Zbinden
Stephen E
SE
Epstein
Charles E
CE
Murry
D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D005109:Extracellular Matrix; D006801:Humans; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods; D020257:Ventricular Remodeling