[Hepatic tissue engineering]

Abstract

Today liver transplantation is the only curative option for the treatment of end-stage liver diseases. A major limitation of liver transplantation is the donor organ shortage. Therefore, tissue engineering based cell transplantation is currently under investigation with the aim to replace liver tissue and function. The principle of tissue engineering is the notion of an interaction between a cell and a three-dimensional matrix. The matrix serves as a scaffold and guides a three-dimensional cell assembly. In addition, the matrix provides for a regulation of cell proliferation and function by cell-matrix interactions. In cultures of hepatocytes a regulation of cell proliferation and specific function by using three-dimensional matrices and by modifying the surface with isolated molecules of the extracellular matrix has been demonstrated. Furthermore, a beneficial effect of a flow bioreactor system on cell viability and function was observed. In addition, a system for heterotopic hepatocyte transplantation on polymeric matrices was developed in an animal model. In this transplantation model a long-term proliferation and function of transplanted hepatocytes was shown. The major limitation of matrix-based transplantation systems is the high initial cell loss, most probably due to an insufficient vascularisation. Thus, the development of vascularised matrices and the creation of bile ducts remain major problems in the technologies of hepatic tissue engineering and have to be addressed to enable further advances towards clinical applications.