Intramyocardial transplantation of human adipose-derived stromal cell and endothelial progenitor cell mixture was not superior to individual cell type transplantation in improving left ventricular function in rats with myocardial infarction

Abstract

Background: Both adipose-derived stromal cells (ASCs) and endothelial progenitor cells (EPCs) have high potential for promoting tissue revascularization and functional recovery in acute myocardial infarction (AMI) models. We investigated the functional effects of intramyocardial transplantation of a human ASC and EPC mixture in immunodeficient rats after MI.

Methods: MI was induced by ligating left anterior descending coronary artery. Survived rats were randomly assigned to 1 of 4 different groups: the control group (n=10, saline in 100μL), the ASC group (n=10, 10(6) ASCs), the EPC group (n=10, 10(6) EPCs), or the ASC+EPC group (n=10, 2×10(5) ASCs+8×10(5) EPCs). Left ventricular (LV) function was compared using echocardiography during the 28-day follow-up. GAP43+ nerve sprouting and smooth muscle α-actin+angiogenesis were also compared.

Results: Serial changes in LV ejection fraction (EF) and fractional shortening revealed significant increases in the ASC, EPC, and ASC+EPC groups when compared to the control group during the follow-up (49±3%, 49±4%, 47±4%, 39±2%, P<0.001, respectively for LVEF) (33±4%, 32±2%, 31±2%, 23±2%, P=0.002, respectively for fractional shortening). The number of α-actin+arterioles and GAP43+ nerve area was significantly greater in the ASC, EPC, and ASC+EPC groups when compared to the control group in the peri-infarct area (34.4±1.0/mm(2), 35.9±1.1/mm(2), 35.3±0.9/mm(2), 17.4±0.7/mm(2), P<0.001, respectively for angiogenesis) (346.2±10.7μm(2)/mm(2), 357.2±12.8μm(2)/mm(2), 368.0±9.7μm(2)/mm(2), 174.6±7.9μm(2)/mm(2), P<0.001, respectively for nerve sprouting).

Conclusions: [corrected] Intramyocardial injections of ASCs, EPCs, or ASCs+EPCs are effective modalities for the treatment of myocardial damage in rats and may expand the potential clinical application of ASC or EPC therapy in patients with ischemic heart disease.