胎肝中肝干细胞的免疫组织化学研究

HISTOCHEMICAL STUDY OF HUMAN FETAL HEPATIC STEM CELLS

目的 采用免疫组织化学方法显示不同时期人胚胎肝脏的干细胞 ,分析肝干细胞的形态与分布特点及发育过程中干细胞在肝脏中的迁徙 ,探讨肝脏的发生发育及肝内干细胞的来源。方法 不同发育时期胎儿肝脏 ,取材、固定、制成石蜡切片 ,ABC法检测肝干细胞特异性的表面标记物CD34、CK19、C - 11和OV6。结果 胎肝内汇管区周边界板处有卵圆样细胞表达CD34、C 11、CK19和OV6 ,阳性细胞紧密排列成管 ,呈鞘样包绕着早期汇管区 ,部分包绕着初级汇管区 ,随着次级汇管区的成熟 ,卵圆样干细胞逐渐局限于赫令氏管周围 ;此外 ,胚胎发育的不同阶段均可见CD34、OV6阳性的单核样细胞分散在肝索、肝血窦之内 ,多见于汇管区的间充质组织之内 ,肝血管内鲜见。结论 胚胎发育早期汇管区周边界板处含有丰富的干细胞 ,可能是肝脏发育的起点 ,这些干细胞逐渐分化为胆管上皮样细胞 ,然后分化为肝细胞和胆管上皮细胞 ;造血干细胞是肝内的另一干细胞来源 ,造血干细胞在肝内受到诱导作用分化为小部分的肝实质细胞。

? Objective To investigate the normal distribution and morphologyof hepatic stem cells in human fetal livers, and to introduce animmunohistochemical method to showthe unique cells during various stages of development. Method ABC staineda biliary epithelial cell expressing protein CK19 and the hematopoietic stem cell marker CD34 at the same time, the rat oval cell marker OV6 and a polyclonal antibody C-11, which arealways expressed on the ductal plate cells, were also positive forthe progenitor cells in fetal livers. Result The hepatic stem cells lying in the limiting plate were co-expressing OV6, CD34,C-11 and CK19. The monolayer unique cells, arrangedtightly into ductules, encapsulatedthe early portal area like a sheath, and partly encapsulatedthe primary portal area. With the development of the secondary portal area, the oval-like stem cells were gradually trending to the Hering canal. In addition, during the various stages of embryogenesis, some mononuclear cells, immunostained by OV6 and CD34, were observedin the hepatic cords and sinusoids, especially in the mesenchymal tissue of portal areas. Conclusion In the early stage of embryogenesis, the limiting plate, which is rich in stem cells, may be the origin of liver development. These cells are thought to have both clonogenic and bipotential capacity - that is, the ability to proliferate and differentiate into either hepatocytes or biliary epithelial cells. There is also evidence that the hematopoietic stem cells may give rise to a new intrahepatic stem cell lineage. The microenvironment in the liver may induce these external stem cells to differentiate into a little part of the hepatic parenchymal cells.