Which Are the Right Cells to be Used in a Bioartificial Liver?

Abstract

Anno 2004 freshly isolated or cryopreserved porcine or human hepatocytes have been most frequently used as bio-component in clinically applied bioartificial livers (BALs). Phase 1 studies of all bio-component modalities showed safety, feasibility, and improvement of biochemical, neurological, and hemodynamic parameters. However, both the pilot-controlled clinical trial with C3A cells and the randomized larger clinical trial with cryopreserved porcine hepatocytes did not show significant improvement of survival by intention-to-treat analysis. Because of the xenotransplantation-related disadvantages of porcine cells and the shortage of primary human hepatocytes, other sources of bio-components have to be explored. The future lies in the development of one or more human hepatocyte cell lines, which will have minimal immunogenicity, no risk of xeno-zoonosis, and the requested functionality and availability. Primary sources for the development of such human cell lines are liver-tumor-derived cell lines, immortalized fetal or adult hepatocytes, and stem cells of hepatic, hematopoietic, or embryonic origin. At present the most promising results for BAL application have been obtained by immortalization of human fetal liver cells by reconstitution of telomerase activity. However, in all cell types tested so far, the in vitro differentiation cannot be stimulated to such an extent that their functionality reaches that of primary human hepatocytes. More insight in differentiation-promoting factors and the influence of matrix and co-culture conditions is needed.