Abstract

We present a three-dimensional perfused flow bioreactor which was designed to recapitulate the in-vivo biomechanical microenvironment of the liver parenchyma with the aim of enhancing the viability of co-cultures of primary rat liver cells in-vitro for use as a toxicology assays in the context of drug screening. Using this same bioreactor, we show that we are able to culture embryonic stem cells on a three-dimensional scaffold while subjecting them to a constant shear stress and inducing cardiomyocyte differentiation through biochemical means. Our preliminary experiments lead us to believe that we are producing vascularised cardiac tissue evidenced by the upregulation of cardiac and endothelial specific genes. Culturing vascularised tissue will enhance the transport of factors and oxygen to all the cultured tissue mass giving us the ability to culture larger volumes of tissue whilst avoiding hypoxia. We are constantly improving the biochemical induction to the cardiac fate while optimising biomechanical forces for optimal de-novo angiogenensis with the aim of producing functional tissue grafts. This tissue provides a more physiologically relevant model for the transplantation immunology studies that are currently ongoing. The natural extension of this work includes generating tissue of other vascularised organs such as the liver and kidney.