Development of strategic therapy for severe hepatic failure using regenerative medicine-Isolation of hepatic stem cell expressing musashi-1 gene and cell therapy

利用再生医学开发严重肝衰竭的策略治疗-表达musashi-1基因的肝干细胞的分离和细胞治疗

• 批准号: 13470112
• 负责人: KAWATA Sumio
• 金额: $ 5.31万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470112/
• 关键词: Hepatic Stem cell; Musashi-1 gene; oval cell; hepatocytes; Hepatoma cell lines; 肝細胞; oval cells

We are trying to develop an innovative therapy for sever hepatic failure to transplant hepatic stem cell. In this therapy, it is an important step to isolate hepatic stem cell expressing musashi-1 gene.In 2001 we established a cell line of oval cells, bipotent stem cells, from rat livers. This cell line expressed musashi-1 gene with AFP and CK-18 ones. With differenciation of the cell line by spheroid formation, the musashi-1 gene expression was suppressed. Moreover, three of seven human hepatoma cell lines expressed musashi-1 gene. This implied that musashi-1 gene might participate in differentiation of hepatic stem cells and hepatic carcinogenesis.In 2002, we found that the musashi-1 gene regulated notch signalin via suppression of Numb gene expression. Also, role of musashi-1 gene in liver development is under investigation using knockout mice of the gene.

我们正在努力开发一种通过移植肝干细胞来治疗严重肝衰竭的创新疗法。2001年，我们从大鼠肝脏中建立了一个卵圆细胞系，即双能干细胞系。该细胞系同时表达musashi-1基因和AFP、CK-18基因。随着细胞系通过球体形成而分化，Musashi-1基因表达被抑制。此外，7个人肝癌细胞系中有3个表达musashi-1基因。2002年我们发现musashi-1基因通过抑制Numb基因的表达来调节Notch信号通路。此外，musashi-1基因在肝脏发育中的作用正在使用基因敲除小鼠进行研究。

项目成果

Sakon M, Nagano H, Kawata S et al.: "Combined intraarterial 5-FU and subcutaneous IFN-αtherapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches"Cancer. 94. 435-442 (2002)

Sakon M、Nagano H、Kawata S 等人：“联合动脉内 5-FU 和皮下 IFN-α 疗法治疗主要门静脉分支中存在肿瘤血栓的晚期肝细胞癌”癌症。 94. 435-442 (2002)

Aoki M., Kawata S., et al.: "Clinical significance of a highly sensitive enzyme immunoassay of hepatitis B surface antigen"J.Med.Virol.. 66. 166-170 (2002)

Aoki M.、Kawata S.等人：“乙型肝炎表面抗原的高灵敏度酶免疫测定的临床意义”J.Med.Virol.. 66. 166-170 (2002)

Tsushima H., Kawata S., et al.: "Circulating TGF-B1 as a predictor of liver metastasis after resection in colorectal cancer"Clin Cancer Res. 7. 1258-1262 (2001)

Tsushima H.、Kawata S. 等人：“循环 TGF-B1 作为结直肠癌切除术后肝转移的预测因子”Clin Cancer Res。

Shu H-J, Saito T, Kawata S, et al.: "Expression of the Musashi1 gene encoding the RNA-binding protein in human hepatoma cell lines"Biochem.Biophys.Res.Commun.. 293. 150-154 (2002)

Shu H-J、Saito T、Kawata S 等人：“编码 RNA 结合蛋白的 Musashi1 基因在人肝癌细胞系中的表达”Biochem.Biophys.Res.Commun. 293. 150-154 (2002)

Saito T, Shinzawa H, Kawata S, et al.: "Home lactulose enema: prevention of hepatic encephalopathy at home"J.Gastroenterol. 97. 493-495 (2002)

Saito T、Shinzawa H、Kawata S 等人：“家庭乳果糖灌肠：在家预防肝性脑病”J.Gastroenterol。