Abstract 367: Combined Effect of Dinitrophenol Preconditioning and Jagged-1 Over-expression in Mesenchymal Stem Cells Improved Cardiomyogenesis and Angiogenesis in Rat Model of Myocardial Infarction

Abstract

Cardiac regeneration following myocardial infarction (MI) largely depends on angiogenesis; an important physiological response that allows the heart to recover. Mesenchymal stem cells (MSCs) can be utilized as a source for cardiac regeneration and angiogenesis using various preconditioning strategies. We investigated the role of cardiomyogenic and angiogenic growth factors combined with preconditioning of MSCs using 2, 4, dinitrophenol (DNP). MSCs were isolated from rat bone marrow and treated with DNP; an uncoupler of oxidative phosphorylation. Based on our earlier report in which we showed that DNP treatment affect the expression of cardiomyogenic and angiogenic factors after different re-oxygenation periods, we selected jagged 1 (Jag1), neuropilin1 (Nrp1), TATA box 20 (Tbx20), and myogenin (Myo) to transfect MSCs. Rat MI models were developed through ligation of left anterior descending coronary artery and confirmed through echocardiographic evaluation 4 weeks post MI. The study was divided into different groups which include control; MI model; and MI groups that received untreated, DNP-treated, transfected-MSCs using the above mentioned growth factors and transfected and DNP-treated MSCs. Functional performance of the hearts was analyzed through echocardiography while regeneration of cardiomyocytes and angiogenesis were observed through histological examination. Significant (p<0.05) improvement in the heart function was observed in case of all treatment groups when compared with the normal MSCs. Histological examination of the heart sections 4 weeks post MI showed that MSCs home towards the site of injury. Most prominent result was observed in case of Jag1-transfected and DNP treated MSCs with heart function comparable to that of the control group. Cardiac regeneration and newly developed blood vessels were prominent in the tissue sections. Significant reduction (p<0.05) in the infarct size was also observed as compared to that in case of Myo, Tbx20 and Nrp1 groups. It is, therefore, concluded that Jag1-transfected MSCs can be a suitable angiogenic factor to be used in combination with DNP for preconditioning of MSCs for future regenerative therapy for cardiomyogenesis.