Abstract 3696: Synergy Between Diprotin A and Genetic Manipulated Cell Sheet Improves Cardiac Function After Myocardial Infarction
CD26/dipeptidylpeptidase IV (DPP-IV) is a protease which reduces cell homing by cleaving SDF-1α. We demonstrated that administration of diprotin A, an inhibitor of DPP-IV, significant enhances engraftment of CXCR4 overexpressing MSCs (CXCR4+-MSCs) from cell sheets to infarcted myocardium. We genetically engineered male rat MSCs over-expressing CXCR4/green fluorescent protein (GFP) (CXCR4 group) or GFP alone (control) or siRNA targeting CXCR4 (siRNA group). Female rats received cell sheets (from UpCell™) wrapped on the surface of infarcted myocardium without (Vehicle group) or with diprotin A (70μg/kg/twice per day for one week, i.p., Diprotin group) immediately after LAD ligation. SDF-1α in heart tissue was measured by ELISA. Efficacy of engraftment was determined by Y-chromosome and GFP. One month after cell implantation, echocardiography was performed and hearts were harvested for histological analysis. LV fibrosis, anterior wall thickness (AWT) and blood vessel density were measured. In heart tissue, there was significant upregulation of SDF-1α in the Diprotin group compared to vehicle group at day 5 after LAD. One month after cell transplantation, the numbers of GFP and Y chromosome positive cells were significantly increased in CXCR4 group and further increased in combination of diprotin A with CXCR4+-MSC patch associated with improvement of left ventricular fibrosis and heart function as compared to control group (Fig. 1⇓). Combination of gene manipulated CXCR4+-MSCs patch with diprotin A provides tissue nutrition (angiogenesis), reduces myocardial remodeling, enhances cell engraftment and improves heart function after myocardial infarction.