Circulation. 2005;112:3174-3183
doi: 10.1161/CIRCULATIONAHA.105.546218
doi: 10.1161/CIRCULATIONAHA.105.546218
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(Circulation. 2005;112:3174-3183.)
© 2005 American Heart Association, Inc.
Basic Science for Clinicians |
Cell-Based Cardiac Repair
Reflections at the 10-Year Point
From the Center for Cardiovascular Biology and Regenerative Medicine, University of Washington, Seattle (C.E.M.); the Herman B. Wells Center for Pediatric Research, Indiana School of Medicine, Indianapolis (L.J.F.); and the Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou and University of Paris 5, INSERM Research Unit 633, Paris (P.M.).
Correspondence to Charles E. Murry, MD, PhD, Center for Cardiovascular Biology and Regenerative Medicine, University of Washington, 815 Mercer St, Seattle, WA 98195. E-mail murry@u.washington.edu
Received February 28, 2005; revision received April 25, 2005; accepted April 29, 2005.
Key Words: heart failure • infarction • transplantation • bone marrow • skeletal myoblast
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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It has now been more than a decade since the first experiments were performed using cell transplantation for the prevention and treatment of heart failure.1–3 Although the biomedical community was initially somewhat skeptical of this approach, a large body of experimental evidence was amassed showing that injected cells could create new tissue and improve function of the failing heart. This evidence, coupled with the recognized limitations of heart failure treatments and the intuitively appealing concept of "regenerative medicine," has contributed to a crescendo of activity in cell-based cardiac repair. Given the flurry of clinical trials that are currently under way, we think it is timely to review progress over the past 10 years and provide a critical assessment of where the field stands and where it appears to be headed.
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The Early Years: Transplantation of Committed Cells in Preclinical Studies |
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Cell-based cardiac repair began with studies of skeletal myoblasts derived from skeletal muscle satellite cells.1–3 Myoblasts were the initial choice because of their availability from autologous or syngeneic sources, their ability to proliferate, and their ability to withstand ischemia better than many cell types. Although it was originally hoped that these cells would transdifferentiate into cardiomyocytes, it is now clear that myoblasts remain stubbornly committed to form mature skeletal muscle in the heart3–5 (with the exception of rare cell fusion events at the graft–host interface6). Skeletal muscle is one of the few cell types in the body that does not normally express gap junction proteins, and hence, structural and physiological studies indicate that skeletal muscle cells do not form
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