Abstract

Tissue engineering is an evolving tool for repair of cardiovascular damage, in particular after myocardial infarction. Currently, most studies are focused on providing gel or thin synthetic matrices to provide structural support for injured valves, or ventricle. But little is known about how cardiac cells (eg, endothelial cells [ECs], cardiomyocytes [CMs] and cardiac progenitor cells [CPCs]) are modified by an exposure to a scaffold much less how a xenogeneic scaffold may affect cell physiology or function. Our study was designed to examine the effect of rat or pig collagen matrix and decellularized left ventricle extracellular matrix (dECM) tissues on the phenotype of human cardiac cells. Human ECs, CMs and CPCs derived from IPs cells (Cellular Dynamics International) were cultured singly or together on rat or pig collagen matrices or on dECM. Protein and gene expression was investigated by immunohistochemistry, histology and real time PCR. All 3 cell types survived on both types of support when delivered singly or together. Endothelial cell PECAM-1 expression was enhanced on decellularized tissues particularly on rat matrix. Cardiomyocyte contractile protein expression did not differ with support type, whereas CPC contractile protein gene expression increased on both decellularized tissues more so on pig matrix. Additionally, when the cells were co-cultured, single cell type gene expression was modified. Our study showed that human cardiac cells are influenced by the structural support on which they are cultivated. Cardiac ECM enhanced the expression of contractile proteins and endothelial markers but matrix species had minimal influence on this effect. Furthermore, cell co-culture altered gene expression suggesting cell communication is intact on the matrix. This study shows that cell phenotype and behavior is impacted by the tissue matrix to a greater degree than occurs with a simple one protein support and suggests complex decellularized matrix may be superior to successfully engineer cardiac constructs with intact physiology. Additionally, the successful differentiation of IPs cells into cardiomyocytes on decellularized matrix opens avenue to build tissue engineer constructs from patients with heart disease as a screening tool.

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