Participation of bone marrow cells in biliary fibrosis after bile duct ligation

Abstract

Bone marrow derived cells are involved in the process of hepatic fibrosis secondary to chronic injury. However, it is not yet known how quickly this event occurs in acute fibrosis models. The purpose of this study was to determine the role of bone marrow cells in rapid fibrosis following bile duct ligation in mice using green fluorescent protein (GFP) expressing bone marrow cells. After whole body irradiation, 1 x 10(6) donor whole bone marrow cells from green fluorescent protein(+/-) mice were transplanted into C57BL/6 recipients via the tail vein. Four weeks after bone marrow transplantation, chimeric mice were subjected to common bile duct ligation, and livers of these animals were histologically examined after bile duct ligation using anti-fibroblast specific protein (FSP)-1 antibody and anti-alpha-smooth muscle actin (alpha-SMA) antibody. Periductal fibrosis consisting of fibroblast specific protein-positive cells was demonstrated histologically as early as day 7. Most of the fibrotic cells were green fluorescent protein-negative, however, a significant number of cells were green fluorescent protein-positive and some were also anti-FSP or alpha-SMA-positive. Differentiation of bone marrow derived cells into activated fibroblast and myofibroblast-like phenotypes occurs in the very early course of periductal fibrosis following bile duct ligation, suggesting a new strategy for prevention of biliary fibrosis by inhibiting migration of bone marrow cells to liver.