Primary Studies on Autologous Marrow Stromal Cells Transplantation Improves Rabbit Cardiac Performance after Myocardiac Infarction

Objective To test the hypothesis that marrow stromal cells(MSCs),when implanted into self-myocardium in rabbits,can undergo milieu-dependent differentiation and express cardiomyogenic phenotypes and enhance cardiac function of ischemic hearts,through establish a clinically relevant model for autologous MSCs transplantation.Methods Thirteen New Zealand White rabbits were randomly divided into experimental group((n=)7) and control group(n=6).In experimental group,autologous MSCs(3×10~6 cells/30μl) labeled with Bromodeoxyuridine(BrdU) were respectively injected into superior,central and inferior sites in the periphery of the myocardial infarct region.Phosphate buffer saline(PBS) was injected into the scar of the control group hearts according to the same procedure used in the experimental group.Four weeks later,the transplanted labeled MSCs were detected by laser scanning confocal microscopy and the cardiac function were examined by echocardiogram and multichannel physiologic recorder.Results After 4 weeks,transplanted MSCs were demonstrated myogenic differentiation with the expression of α-sarcomeric actin and connexin 43 located in intercalated disk.MSCs increased the number of vessels compared with controls in myocardial ischemia area.MSCs implantation resulted in markedly improved left ventricular contractility[left ventricular ejection fraction(LVEF): 0.51±0.07 vs.0.43±0.06,left ventricular lateral wall motion distance(LVLWMD):1.75±0.42mm vs.1.09±0.28mm,left ventricular systolic wall thickening ratio(LVΔT):0.19%±0.05% vs.0.11%±0.04%,left ventricular systolic pressure(LVSP): 113.1±6.3mmHg vs.99.5±5.1mmHg,left ventricular end diastolic pressure(LVEDP): 11.5±2.1mmHg vs.14.3±3.1mmHg,maximum rate of left ventricular pressure rise (+dp/dt_(max)):4 618.3±365.2 mmHg/s vs.3 268.1±436.9 mmHg/s,maximum rate of left ventricular pressure fall(-dp/dt_(max)):3 008.8±346.7 mmHg/s vs.2 536.9±380.4 mmHg/s,P0.05].Conclusion Transplanted autologous MSCs are able to undergo differentiation to form myocardial cells and improve the cardiac function of ischemia myocardium effectively.Autologous MSCs transplantation may have significant clinical potential in treatment myocardial ischemia.