Development of liver regeneration therapy against severe hepatic failure based on stem cell science -Differentiation and growth of hepatic stem cell and cell transplantation.

基于干细胞科学的针对严重肝衰竭的肝再生疗法的发展-肝干细胞的分化和生长以及细胞移植。

• 批准号: 15390224
• 负责人: KAWATA Sumio
• 金额: $ 8.7万
• 依托单位: Yamagata 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-15390224/
• 关键词: Liver regeneration; Hepatic stem cells; oval cells; Musashi-1 gene; Notch signal; Matrigel; bone marrow cells; GFP transgenic mice; Musashi-1; GFPトランスジェニック・マウス; oval cell line; Musashi-1遺伝子; natchシグナル

We are trying to develop an innovative therapy for severer hepatic failure to transplant hepatic stem cells. In this therapy, It is an important step to isolate hepatic stem cells expressing Musashi-1 gene.In 2003 we showed that oval cells, a cell lineage of hepatic stem cells, expressed Musashi-1 gene in rat liver injury model. The expression of Musashi-1 gene in oval cells was regulated by signal transduction pathways through notch and jagged 1.In 2004, we development of culture system using Matrigel, in which bone marrow cells could differentiated into phenotype of hepatocytes. Bone marrow cells expressed hepatocyte-specific genes such as albumin, AFP, cytokeratin 8, and tryptophan-2,3-dioxygenease. Further, the cells on Matrigel showed hepatic cord-like structure.This study demonstrated findings as follows : 1)there exist bone marrow cell which can differentiate into hepatocyte-phenotype, 2)transplanted bone marrow cells could anchor in the liver when the liver injury was severe, 3)bpne marrow cell could effectively grow and differentiate into hepatocytes on Matrigel.

我们正在努力开发一种新的治疗方法，即肝干细胞移植。2003年我们在大鼠肝损伤模型中发现了肝干细胞的一个细胞系--卵圆细胞表达Musashi-1基因。Musashi-1基因在卵圆细胞中的表达是通过notch和jagged 1信号转导途径调节的。2004年，我们利用Matrigel建立了骨髓细胞向肝细胞分化的培养体系。骨髓细胞表达肝细胞特异性基因，如白蛋白、AFP、细胞角蛋白8和色氨酸-2，3-双加氧酶。本研究结果表明：1）骨髓中存在可向肝细胞分化的细胞; 2）肝损伤严重时，移植的骨髓细胞可在肝内锚定; 3）骨髓细胞在Matrigel上能有效生长并分化为肝细胞。

项目成果

Okumoto K, Kawata S, et al.: "Differentiation of bone marrow cells into cells that express liver-specific genes in vitro"Biochem.Biophys Res Commun.. 304. 691-695 (2003)

Okumoto K、Kawata S 等人：“骨髓细胞分化为在体外表达肝脏特异性基因的细胞”Biochem.Biophys Res Commun.. 304. 691-695 (2003)

Watanabe H, Saito T, et al.: "Spontaneous elimination of serum HCT RNA in chronic HCV carriers"J.Med Virol. 71. 56-61 (2003)

Watanabe H、Saito T 等人：“慢性 HCV 携带者血清 HCT RNA 的自发消除”J.Med Virol。

Expression of Notch signal markers in bone marrow cells that differentiate a Liver cell lineage in a rat transplant model.

Notch 信号标记在骨髓细胞中的表达，可在大鼠移植模型中区分肝细胞谱系。

• 发表时间: 2005
• 期刊: Hepatol Res 31
• 作者: Okumoto K;Kawata S;et al.
• 通讯作者: et al.

Hattori E, Kawata S, et al.: "Possible contribution of circulating IL-10 to prognosis in patients with HCC"Hepatology Res. 27. 309-314 (2003)

Hattori E、Kawata S 等人：“循环 IL-10 对 HCC 患者预后的可能贡献”Hepatology Res。

Expression of Notch signaling markers in bone marrow cell that differentiate Into a liver cell lineage in a rat transplant model.

在大鼠移植模型中分化成肝细胞谱系的骨髓细胞中Notch信号标记的表达。

• 发表时间: 2005
• 期刊: Hepatol Res 31
• 作者: Okumoto K;Kawata S;et al.
• 通讯作者: et al.