The human progenitor cell niche: research on differentiation mechanisms.

Hepatocytes are crucial for processing dietary nutrients, protein synthesis, detoxification and excretion of toxins. When hepatocyte function ceases, acutely or chronically, the only curative therapy is liver transplantation. Due to organ shortage new therapeutic modalities should be looked for. Aside from use of hepatocytes as therapeutic agents, they are used extensively for drug testing and to develop therapies for viral hepatitis. Liver specific adult stem cells hold great promise for the generation of hepatocytes; the differentiation mechanisms are however poorly understood, hampering development of new therapies sustaining liver regeneration. Being able to sustain the enormous regenerative capacity of the liver would replace transplantation in a number of patients. Prof. Verfaillie already generated cells with features of fetal hepatocytes from embryonic stem cells (ESCs). Terminal differentiation of these cells is not yet possible. Using laser microdissection in vivo of stem cells and their progeny, Prof. Roskams' group already characterized signaling pathways involved in their differentiation towards hepatocytes and cholangiocytes respectively. Further work on different diseases will complete the picture. In parallel, Prof. Verfaillies group can test in her in vitro ESC differentiation system new growth factors/molecules for the possible future use in sustaining regenerative therapies.

Keywords:Hepatocyte, Liver stem cells, Liver progenitor cells, Differentiation, Liver regeneration, Signaling pathways, Embryonic stem cells

Disciplines:Laboratory medicine