The emerging role of hematopoietic stem cells in liver pathogenesis and regeneration

Hematopoietic stem and progenitor cells (HSCs), which express CD34 antigen, circulate at a very low frequency in peripheral blood in steady state. HSCs have been believed to differentiate to a variety of cells in certain conditions, however, the role of HSCs in liver diseases and regeneration has not been well elucidated. Therefore we investigated the mobilization of HSCs and differentiation of HSCs in liver in the several hepatic conditions. We have investigated the numbers of circulating HSCs by flow cytometry and methylcellulose culture, in human various liver disease and regeneration with liver transplantation patients. We also examined the differentiation of HSC in mouse liver injury model. Numbers of circulating HSCs were significantly diminished with progression of liver disease. We have also found circulating HSCs increased after liver transplantation patients and donors with hepatectomy. In addition, the numbers of circulating HSCs and platelets increased significantly after splenectomy and the enhancing effect persisted for a long time. Mouse model experiments suggested that HSCs contribute to the generation of hepatic stellate cells after carbon tetrachloride-induced injury liver injury and macrophages after MCD diet-induced fatty liver. In conclusions, HSCs play an important role in liver regeneration and hepatic pathogenesis. Differentiation of HSCs may be dependent on liver conditions.