Cardiomyocyte transplantation into the failing heart-new therapeutic approach for heart failure?
Heart failure, frequently the consequence of irreversible myocardial damage with subsequent formation of akinetic scar tissue, is a highly prevalent disease, and in its advanced stages associated with high mortality. The transplantation of exogenous cells with the inherent ability to contract has been put forward as one potential treatment strategy to increase contractility and cardiac performance. Besides skeletal myoblasts or stem cells from various sources, immature cardiomyocytes, such as fetal or neonatal cardiomyocytes, have been transplanted into normal, cryoinjured, infarcted myocardium, as well as into models of global heart failure. Survival of transplanted immature cardiomyocytes has been demonstrated up to 6-7 months, accompanied by vascularization of the grafted tissue. Transplants developed sarcomeric structures and other morphological features of differentiation. The principal possibility of cell-to-cell coupling between graft and host cells was demonstrated after cardiomyocyte transplantation into normal hearts and in some studies in damaged myocardium. But most long-term follow-up investigations in models of myocardial infarction reported that optimal integration of the engrafted cells appeared to be hindered by scar tissue, separating the transplant from the host. Nonetheless, in several studies, improved parameters of cardiac performance were demonstrated ex-vivo and in vivo. Potential mechanisms might involve beneficial effects on the remodeling process. In this review, we critically evaluate the potential value of cardiomyocyte transplantation as a new approach in the treatment of the syndrome of "heart failure".
Reffelmann
Thorsten
T
The Heart Institute, Good Samaritan Hospital, University of Southern California, Los Angeles, CA 90017-2395, USA.
Leor
Jonathan
J
Müller-Ehmsen
Jochen
J
Kedes
Larry
L
Kloner
Robert A
RA
D000818:Animals; D017690:Cell Transplantation; D005318:Fetal Heart / Q000166:cytology* / Q000473:pathology / Q000601:surgery; D016332:Fetal Tissue Transplantation; D006333:Heart Failure / Q000453:epidemiology / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D015994:Incidence; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000473:pathology / Q000637:transplantation*; D009336:Necrosis