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Transplantation of hepatocyte-like cells differentiated from ES cells

ES细胞分化的肝细胞样细胞移植

基本信息

批准号：
13470232
负责人：
TERAMOTO Kenichi
金额：
$ 8.9万
依托单位：
Tokyo Medical and Dental 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 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470232/
关键词：
mouse embryonic stern cell hepatocyte differentiation umbilical cord blood cell transplantation liver failure cell differentiation 再生医学 ES細胞ヒト臍帯血由来細胞 stem cell teratoma 幹細胞肝再生

项目摘要

1)A study of induction of hepatocytefrom ES cellWe have succeeded in inducing albumin-producing cell through EB from ES cell. These cell had a ability of producing urea. Taken these together, these cells are considered to be hepatocyte. This hepatocyte-like cell was transplanted into C57BL/6 mouse which had liver injury in advance. The transplanted cell grew up in the recipient liver and produced albumin. But, teratoma formation was seen in 20-30% mouse. The cell was selected in order to suppress teratoma. First, the single layer cell culture from EB was performed, and isolated. The cell was selected by specific gravity by the ercoll method. This cell group was negative in oct 3/4. When this cell was transplanted to an above-mentioned liver injury model mouse, teratoma formation was not recognized. As mentioned above, recovery of the cell group which does not generate teratoma from an embryonic stem cell was attained. Furthermore, it became possible by removing other blood cell ingredients for this cell group using FAGS and MACS to obtain many albumin positive cells.2) ES cell of cynomolgus monkeyAiming at clinical application of embryonic stem cell, induction of a liver cell was tried from cynomolgus monkey embryonic stem cell. Although a different method of induction from a mouse embryonic stem cell was required for induction of cynomolgus monkey stem cell, albumin-producing cell was able to be induced by our method.3) Induction of hepatocyte from umbilical cord bloodWe succeeded in liver cell induction from umbilical cord blood. Two cell types were recognized, one is expressing albumin and CK-18 and the other is expressing albumin and CK-19. Now, we are studying bile duct epithelium cell induction from umbilical cord blood.

1)ES细胞诱导产生肝细胞的研究我们成功地从ES细胞中分离出EB诱导产生白蛋白的细胞。这些细胞具有产生尿素的能力。综合起来，这些细胞被认为是肝细胞。将该肝细胞样细胞移植到预先发生肝损伤的C57BL/6小鼠体内。移植的细胞在受体肝脏中生长，并产生白蛋白。但有20-30%的小鼠有畸胎瘤形成。选择该细胞是为了抑制畸胎瘤。首先，进行EB单层细胞培养，并进行分离。用Ercoll法按比重法选择细胞。将该细胞移植到上述肝损伤模型小鼠体内，未见畸胎瘤形成。如上所述，实现了从胚胎干细胞中恢复不产生畸胎瘤的细胞组。2)食蟹猴ES细胞针对胚胎干细胞的临床应用，尝试从食蟹猴胚胎干细胞中诱导出肝细胞。虽然诱导食蟹猴干细胞需要不同的小鼠胚胎干细胞的诱导方法，但我们的方法能够诱导产生白蛋白的细胞。3)从脐带血中诱导肝细胞我们成功地从脐带血中诱导出了肝细胞。有两种细胞类型，一种是表达白蛋白和CK-18，另一种是表达白蛋白和CK-19。目前，我们正在研究从脐带血中诱导出胆管上皮细胞。