Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction.
BACKGROUND
Adipose-derived stem cells (ADSCs) are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function.


METHODS
ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscoves modified dulbeccos medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs (UASCs, n = 14), 5-azacytidine-pretreated ADSCs (AASCs, n = 13), or phosphate buffer saline (n = 13) were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation.


RESULTS
ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak +dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak +dP/dt values than did UASC-implanted hearts.


CONCLUSIONS
ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for augmenting myogenesis. Transplantation of 5-azacytidine-treated ADSCs into the myocardial scar was more efficient than that of untreated ADSCs in preservation of cardiac function.
Zhang
Duan-zhen
DZ
Department of Cardiology, General Hospital of Shenyang Military Region, Shenyang 110016, China.
Gai
Lu-yue
LY
Liu
Hong-wei
HW
Jin
Qin-hua
QH
Huang
Jian-hua
JH
Zhu
Xian-yang
XY
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002478:Cells, Cultured; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D011817:Rabbits; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left
D001374:Azacitidine