A Role of somatic stem cells in pathogenesis and treatments of hereditary hepatic disorders.

研究发病机制和寻求新的治疗方法需要从新的角度出发。对于肝脏疾病的治疗，相信使用胰岛细胞系统是有希望的。从ES细胞或体干细胞诱导内胚细胞，例如肝细胞或胰腺细胞。(1)In本研究是对细胞损伤过程中基因表达的研究的扩展。（2）遗传性酪氨酸血症1型，一种由富马酰乙酰乙酸水解酶（FAH）缺乏引起的遗传性疾病，引起严重的内脏损伤。FAH缺乏的小鼠在出生后是致命的;因此，阐明疾病过程机制的努力受到阻碍。Fah（-/-）Hpd（-/-）双突变小鼠的使用使得酪氨酸血症的研究成为可能，并且已经揭示了内脏损伤的基本特征。在这个小鼠模型中，我们移植了从唾液腺分离的内胚层体干细胞。两周后，解剖肝脏并分析再增殖。结果表明，20-40%的肝细胞被移植细胞所替代，提示内胚层干细胞将代表成体的内胚层干细胞。

Researches on pathogenesis and quest for new treatments require approaches from vew view points. For treatment of liver disease, employment of stam cell systems are believed to be hopeful. Induction of endodermal cells such as liver cells or pancreatic cells, from ES cells or somatic stem cells.(1)In the present study, we extended previous investigations on the gene expression during the process of cell injury.(2)Hereditary tyrosinemia type 1, a genetic disease caused by a deficiency of fumarylacetoacetate hydrolase(FAH), induces severe visceral injuries. Mice with FAH deficiency are lethal after birth ; thus, efforts to elucidate the mechanisms of the disease process have been impeded. The use of Fah(-/-) Hpd(-/-) double-mutant mice has enabled studies on tyrosinemias, and essential features of visceral injury have been revealed. In this mice models, we transplanted endodermal somatic stem cells isolated from salivary glands. Two weeks after, the livers Were dissected and analysed for repopulation. The results indicated 20-40% of hepatic cells are replaced by transplqabted cells.The results presented here suggested that endodermal stem cells will represent the endodermal stem cells of adults.