Prospects for cell-based therapies for liver disease

Liver parenchymal maintenance and regeneration after injury are physiologically supported by 3 cell compartments: mature liver cells, intra-organ stem cells such as cells of the proximal biliary tree and periductal cells, and extra-organ stem cells from the circulation and the bone marrow. In the latter case, hepatocyte derivation from circulating cells (plasticity) can arise via direct transdifferentiation (site specific, receptor/ligand dependent) or by fusion of circulating cells with pre-existing hepatocytes. Other non-physiologic stem cells, such as mesenchymal stem cells from the bone marrow and embryonic stem cells, may be potentially used in treatment of inherited and acquired liver diseases. This review updates our current understanding of these various cell populations and of possible approaches to their future therapeutic uses in cell transplantation, bioartificial liver devices, cytokine/chemokines manipulation of physiological repair pathways, and gene therapy.