Exogenous ECM in an environmentally-mediated in vitro model for cardiac fibrosis.

Abstract

Few clinical solutions exist for cardiac fibrosis, creating the need for a tunable in vitro model to better understand fibrotic disease mechanisms and screen potential therapeutic compounds. Here, we combined cardiomyocytes, cardiac fibroblasts, and exogenous extracellular matrix (ECM) proteins to create an environmentally-mediated in vitro cardiac fibrosis model. Cells and ECM were combined into 2 types of cardiac tissues- aggregates and tissue rings. The addition of collagen I had a drastic negative impact on aggregate formation, but ring formation was not as drastically affected. In both tissue types, collagen and other ECM did not severely affect contractile function. Histological analysis showed direct incorporation of collagen into tissues, indicating that we can directly modulate the cells' ECM environment. This modulation affects tissue formation and distribution of cells, indicating that this model provides a useful platform for understanding how cells respond to changes in their extracellular environment and for potential therapeutic screening.