Gene expression profiles following intracoronary injection of mesenchymal stromal cells using a porcine model of chronic myocardial infarction

Abstract

Background aims. We evaluated the therapeutic potential of injection of in vitro differentiated bone marrow mesenchymal stromal cells (MSC) using a swine model. Methods and Results. Myocardial infarction was induced by coronary occlusion. Three groups (n = 5 each) were analyzed: one group received an injection of 17.8 ± 9.3 × 10⁶ 5-azacytidine-treated allogeneic MSC 1 month after infarction; a placebo group received an injection of medium; and controls were kept untreated. After 4 weeks, heart samples were taken from three infarcted areas, interventricular septa, ventricles and atria. Gene expression profiles of genes related to contractility (Serca2a), fibrosis (Col1a1), cardiomyogenesis (Mef2c, Gata4 and Nkx2.5) and mobilization of stem cells (Sdf1, Cxcr4 and c-kit) were compared by quantitative real-time PCR (qRT-PCR). Gene expression profiles varied in different heart areas. Thus Serca2a expression was reduced in infarcted groups in all heart regions except for the left ventricles, where Col1a1 was overexpressed. The expression of genes related to cardiomyogenesis decreased in the infarcted zones and left atria compared with healthy hearts. Interestingly, increased expression of Cxcr4 was detected in infarcted regions of MSC-treated pigs compared with the placebo group. Conclusions. Infarction induced changes in expression of genes involved in various biologic processes. Genes involved in cardiomyogenesis were downregulated in the left atrium. The intracoronary injection of MSC resulted in localized changes in the expression of Cxcr4.

Key Words::

• cell transplantation
• gene expression
• mesenchymal stromal cells
• pig

Acknowledgments

We would like to acknowledge Purificación Filgueira and María Fraga for sample collection and tissue staining, Patricia Añón for cell culturing and labeling, and Sonia Pértega, who helped with statistical analyzes.

This work was supported by the ‘Fondo de Investigación Sanitaria’ [PI061607], the ‘Xunta de Galicia’ (PGIDTIT07PXIB916203PR) and the ‘Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina’ (CIBER-BBN-CB06/01/0040).

Conflict of interest: None.