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Background Adipose-derived stem cells(ADSCs)are capable of differentiating into cardiomyogenic and endothelialcells in vitro.We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infractedmyocardium and restore cardiac function.Methods ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscove’s modifieddulbecco’s medium.Three weeks after ligation of left anterior descending coronary artery of rabbits,either a graft ofuntreated 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 5weeks after cell transplantation.Results ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29,CD44 and CD105.Fiveweeks 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 inthe middle of the scar and UASCs,in contrast,were poorly differentiated.Some ADSCs were differentiated intoendothelial cells and participate in vessel-like structures formation.All the ADSC-implanted hearts had a greater capillarydensity in the infarct region than did the control hearts.Statistical analyses revealed significant improvement in leftventricular ejection fraction,myocardial performance index,end-diastolic pressure,and peak +dP/dt,in two groups ofADSC-implanted hearts relative to the control hearts.AASC-implanted hearts had higher peak -dP/dt values than didcontrol,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 foraugmenting myogenesis.Transplantation of 5-azacytidine-treated ADSCs into the myocardial scar was more efficientthan that of untreated ADSCs in preservation of cardiac function.Chin Med J 2007;120(4):300-307
Background Adipose-derived stem cells (ADSCs) are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of myocardial infarcted myocardium and restore cardiac function. Methods ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscove’s modified dulbecco’s medium.Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of atreated ADSCs (UASCs, n = 14), 5-azacytidine-pretreated ADSCs (AASCs, n = 13) Transcription buffer saline (n = -13) were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks later after cell transplantation. Results ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Fiveweeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts.Many ADSCs were differentially ated into cardiomyocytes. The AASCs in the prescar have more myotube-like. AASCs inthe middle of the scar and UASCs, in contrast, were poorly differentiated.Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures.All the ADSC- implanted hearts had a greater capillary density in the infarct region than did the control hearts.Statistical analyzes showed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak + dP / dt, in two groups of ADC-implanted hearts relative to control the hearts. AASC-implanted hearts had higher peak-dP / dt values than did uncontrol, 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 vessels -like structures, induced angiogenesis and improved cardiac function.5-Azacytidine pretreatment before implantation is desirable foraugmenting myogenesis. Thansplantation of 5-azacytidine-treated ADSCs into the myocardial scar was more efficient that of untreated ADSCs in preservation of cardiac function. Chin Med J 2007; 120 (4): 300-307