Transplantation of cardiac progenitor cell sheet onto infarcted heart promotes cardiogenesis and improves function.
OBJECTIVE
Cell-based therapy for myocardial infarction (MI) holds great promise; however, the ideal cell type and delivery system have not been established. Obstacles in the field are the massive cell death after direct injection and the small percentage of surviving cells differentiating into cardiomyocytes. To overcome these challenges we designed a novel study to deliver cardiac progenitor cells as a cell sheet.


RESULTS
Cell sheets composed of rat or human cardiac progenitor cells (cardiospheres), and cardiac stromal cells were transplanted onto the infarcted myocardium after coronary artery ligation in rats. Three weeks later, transplanted cells survived, proliferated, and differentiated into cardiomyocytes (14.6 +/- 4.7%). Cell sheet transplantation suppressed cardiac wall thinning and increased capillary density (194 +/- 20 vs. 97 +/- 24 per mm(2), P < 0.05) compared with the untreated MI. Cell migration from the sheet was observed along the necrotic trails within the infarcted area. The migrated cells were located in the vicinity of stromal-derived factor (SDF-1) released from the injured myocardium, and about 20% of these cells expressed CXCR4, suggesting that the SDF-1/CXCR4 axis plays, at least, a role in cell migration. Transplantation of cell sheets resulted in a preservation of cardiac contractile function after MI, as was shown by a greater ejection fraction and lower left ventricular end diastolic pressure compared with untreated MI.


CONCLUSIONS
The scaffold-free cardiosphere-derived cell sheet approach seeks to efficiently deliver cells and increase cell survival. These transplanted cells effectively rescue myocardium function after infarction by promoting not only neovascularization but also inducing a significant level of cardiomyogenesis.
Zakharova
Liudmila
L
Cardiovascular Research Laboratory, Center for Cardiovascular Research, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA.
Mastroeni
Diego
D
Mutlu
Nezahet
N
Molina
Michelle
M
Goldman
Steven
S
Diethrich
Edward
E
Gaballa
Mohamed A
MA
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D018920:Coculture Techniques; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D024510:Muscle Development; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012038:Regeneration; D033581:Stem Cell Transplantation; D013318:Stroke Volume; D017154:Stromal Cells / Q000637:transplantation; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
D054377:Chemokine CXCL12