Gene Expression Profiles in a Porcine Model of Infarction: Differential Expression After Intracoronary Injection of Heterologous Bone Marrow Mesenchymal Cells

Abstract Myocardial infarction is one of the main causes of mortality in developed countries. Injection of bone marrow mesenchymal stem cells (BMMSC) with the ability to regenerate lost cardiomyocytes is a promising therapy for heart failure. To evaluate this strategy, an in vivo porcine model of infarction was used. Gene expression profiles of 3 groups of pigs (n = 5 each) were analyzed and compared by real-time reverse transcription-polymerase chain reaction (RT-PCR). One of the groups underwent anterior descending coronary occlusion followed by BMMSC injection; a placebo group was injected with culture medium without cells after infarction; and a third group was formed by healthy pigs. Four weeks later, cells or medium was administered by intracoronary injection and, a month later, animals were sacrificed and samples collected. Genes related to cardiomyogenesis ( Mef2C, Gata4, Nkx2.5 ), mobilization and homing of resident or circulating stem cells ( Sdf1, Cxcr4, c-Kit ), contractibility ( Serca2a ), and fibrosis ( CollA1 ) were analyzed. Gene expression profiles changed in various heart areas in the 3 groups. Expression of genes related to cardiomyogenesis decreased in infarcted zones compared with homologous regions of healthy hearts. Sdf1 expression increased in the apex of infarcted hearts. Serca2a expression was reduced in the ventricles and atria of infarcted hearts. Also, increases in Cxcr4 and CollA1 expression were observed in infarcted hearts of cell-treated pigs compared with the placebo group. In conclusion, infarction induced changes in genes involved in various biological processes. Intracoronary injection of heterologous BMMSC resulted in localized changes in the expression of Cxcr4 and Col1A1.