Effect of Intracoronary Infusion of Bone Marrow Mononuclear Cells or Peripheral Endothelial Progenitor Cells on Myocardial Ischemia-reperfusion Injury in Mini-swine

Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model.Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol.About(3.54±0.90)×108 bone marrow mononuclear cells(MNC group,n=9) or(1.16± 1.07)×107 endothelial progenitor cells(EPC group,n=7) was infused into the affected coronary segment of the swine.The other mini-swine were infused with phosphate buffered saline as control(n=7).Echocardio-graphy and hemodynamic studies were performed before and 4 weeks after cell infusion.Myocardium infarction size was calculated.Stem cell differentiation was analyzed under a transmission electromicroscope.Results Left ventricular ejection fraction dropped by 0% in EPC group,2% in MNC group,and 10% in the control group 4 weeks after cell infusion,respectively(P<0.05).The systolic parameters increased in MNC and EPC groups but decreased in the control group.However,the diastolic parameters demonstrated no significant change in the three groups(P>0.05).EPC decreased total infarction size more than MNC did(1.60±0.26 cm2 vs.3.71±1.38 cm2,P<0.05).Undermature endothelial cells and myocytes were found under transmission electromicroscope.Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function,but might not has obvious effect on diastolic function.Intracoronary infusion of EPC might be better than MNC in controlling infarction size.Both MNC and EPC may stimulate angiogenesis,inhibit fibrogenesis,and differentiate into myocardial cells.

IMPLANTATION OF AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS INTO ISCHEMIC MYOCARDIUM ENHANCES CORONARY CAPILLARIES AND SYSTOLIC FUNCTION IN MINISWINE

Objective To investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction. Methods Sixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54±0.90)×108 BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation. Results In BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or +dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and +dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and –dp/dtmax did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 ± 6.96)/high power field vs. (3.50 ± 1.90)/high power field, P < 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P < 0.05). Conclusions Transplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.