Hematopoietic cells as hepatocyte stem cells: A critical review of the evidence

The authors reviewed 77 published reports available before August 1, 2005 that examined the ability of hematopoietic cells to generate hepatocytes in the liver. A list of these publications and a synopsis of each are available on-line. We interpret the evidence provided by this data set to suggest that one or more types of hematopoietic cells may rarely acquire the hepatocyte phenotype in the liver (frequency <= 10(-4)), although the nature of the hematopoietic cells involved and the mechanisms responsible for acquisition of a hepatocyte phenotype are still controversial. Hematopoietic stem cells do not appear to be direct precursors of hepatocytes, which, instead, can be generated from cells of the macrophage-monocyte lineage. Fusion between hepatocytes and transplanted hematopoietic cells has been substantiated as a mechanism by which hepatocytes that carry a bone marrow tag are generated, but direct transdifferentiation of hematopoietic cells has not been demonstrated. In conclusion, hematopoietic cells contribute little to hepatocyte formation under either physiological or pathological conditions, although they may provide cytokines and growth factors that promote hepatocyte functions by paracrine mechanisms. Cells of the endodermal hepatocyte lineage are far more potent generators of hepatocytes than are hematopoietic cells. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-91391suppmat/ index.html).