Role of bone marrow derived cells in progression of hepatic fibrosis.

骨髓源性细胞参与慢性损伤继发性肝纤维化的过程。然而，目前尚不清楚该事件在急性纤维化模型中的发生速度。本研究的目的是利用嵌合绿色荧光蛋白表达骨髓细胞，确定骨髓细胞在小鼠胆管结扎后快速纤维化中的作用。方法：全身照射后，将绿色荧光蛋白^+/-小鼠供体全骨髓细胞1 × 106个经尾静脉移植到C57BL/6受体体内。骨髓移植后4周，对嵌合小鼠进行胆总管结扎，用抗成纤维细胞特异性蛋白-1抗体和抗-平滑肌肌动蛋白抗体对结扎后的肝脏进行组织学检查。结果：早在第7天，组织学上就证实了由成纤维细胞特异性蛋白阳性细胞组成的导管周围纤维化。大多数纤维化细胞呈绿色荧光蛋白阴性，但有相当数量的细胞（10%）呈绿色荧光蛋白阳性，部分细胞也呈抗成纤维细胞特异性蛋白-1或α -平滑肌肌动蛋白阳性。结论：骨髓源性细胞分化为活化成纤维细胞和肌成纤维细胞样表型发生在胆管结扎后导管周围纤维化的早期过程中。

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 chimeric green fluorescent protein expressing bone marrow cells.METHODOLOGY : After whole body irradiation, 1 × 106 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-1 antibody and anti-alpha-smooth muscle actin antibody.RESULTS : 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 (10%) were green fluorescent protein-positive and some were also anti-fibroblast specific protein-1- or alpha-smooth muscle actin-positive.CONCLUSIONS : Differentiation of bone marrow derived cells to activated fibroblast and myofibroblast-like phenotypes occurs in the very early course of periductal fibrosis following bile duct ligation.