Development of tissue bioengineering techniques for the functional reconstruction of ex vivo iPSC cell livers

Abstract

The liver is an important organ with several essential functions for keeping the hysiological homeostasis. Currently, the liver transplantation is an alternative therapy to patients with irreversible hepatic injuries. This process is complex due limited available donors, as well as the difficulty of immunological compatibility. Considering the stem-cells differentiation abilities towardseveral cell-types and methodological advances to the enrichment and use of the ultrastructureof decellularized organ matrices for repopulation (organs reconstruction by cell perfusion), the aim of this work is the development and improvement of bioengineering methods which could allow the ex vivo reconstruction of a functional liver. For that, livers from Wistar rats (250-300g)will be descellularized. The liver matrices (extracellular matrix ultrastructure) will be enriched with proteins from human liver cells conditioned medium (CM). Similarly, hepatoblastos, hepatocytes endothelial cells and MSCs will be differentiated from iPSCs for recellularization of decellularized liver matrices. The recellularization procedure will be evaluated by immunohistochemistry and thefunctionality of the new organ will assessed by dosaging of liver cell molecules yield.