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

成体干细胞在遗传性肝病发病机制和治疗中的作用。

• 批准号: 15390113
• 负责人: ENDO Fumio
• 金额: $ 9.86万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390113/
• 关键词: liver failure; amino acid metabolism; enzyme defect; cancer; mouse model; apoptosis; 遺伝性疾患

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.

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层细胞，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。

项目成果

Endo F, et al.: "Animal models for tyrosinemias reveal pathophysiologies of tyrosinemias."J Nutrition. 133. 2063S-2067S (2003)

Endo F 等人：“酪氨酸血症的动物模型揭示了酪氨酸血症的病理生理学。”J Nutrition。

Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages

• DOI: 10.1053/jhep.2003.50259
• 发表时间: 2003-07-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Okumura, K;Nakamura, K;Endo, F
• 通讯作者: Endo, F

Serum cytocheome C level as a prognostic indicator in patients with systemic inflammatory response syndrome.

血清细胞化学C水平作为全身炎症反应综合征患者的预后指标。

• 发表时间: 2004
• 期刊: Clinica Chimica Acta 342
• 作者: Adachi N.;Endo F.;et al.
• 通讯作者: et al.

In situ evaluation of podochin n normal and glomerular diseases.

正常和肾小球疾病中 podochin 的原位评估。

• 发表时间: 2003
• 期刊: Kidney Int. 64
• 作者: Horinouchi I.;Nakazato H.;Kawano T.;Iyama K.;Furuse A.;Arizono K.;Machida J.;Sakamoto T.;Endo F.;Hattori S.
• 通讯作者: Hattori S.

Hisatomi Y., Endo F., et al.: "Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages."Hepatology. 39. 667-675 (2004)

Hisatomi Y.、Endo F. 等人：“通过流式细胞术分离小鼠唾液腺中的内胚层祖细胞，分化为肝和胰谱系。”肝病学。