Development of method of transdifferentiation of human umbilical cord blood cells to hepatocyte

人脐带血细胞向肝细胞转分化方法的研制

• 批准号: 14570469
• 负责人: SHIOTA Goshi
• 金额: $ 2.24万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570469/
• 关键词: umbilical cord blood cell; stem cell; hepatocyte; transdifferentiation; induction; 臍帯血; CD34; CD38; c-kit

Umbilical cord blood contains many types of stem cells. One kind of stem cells in cord blood can transdifferentiate into hepatocytes. Therefore, cord blood cells contain hepatocyte-progenitor cells or stem-like cells. It is very important to identify these progenitor cells in order to develop regenerative medicine in the field of hepatology. We tried to identy these cells in human cord cells using NOD/SCID mice. After depletion of CD&positive cells, CD34, CD38 and c-kit were used for isolation of stem cells. These cells were introduced into NOD/SCID mice after acute liver injury, and were assessed to transdifferentiate into hepatocyte using human albumin mRNA as a marker. As a result, CD34-positive cells contain many hepatic progenitor cells, and CD34-positive, CD38-positive cells and CD-34-positive, CD-38-negative cells are different in the time of transdifferentiation. cidt is not a useful marker in isolating hepatic progenitor cells. Fish method identified that both fusion cells of human cord blood cells and mouse hepatocytes and transdifferentiated cells from cord blood cells to hepatocytes actually exist. Importnatly, both cells express human albumin. These data suggest that hepatocyte-like cells are composed of trnasdifferentiated hepatocyte and fused cells between cord blood cells and hepatocytes.

脐带血含有多种类型的干细胞。脐带血中有一种干细胞可以转分化为肝细胞。因此，脐带血细胞含有肝细胞祖细胞或干细胞样细胞。为了在肝病学领域发展再生医学，鉴定这些祖细胞是非常重要的。我们试图用NOD/SCID小鼠在人脐带细胞中鉴定这些细胞。去除CD+细胞后，使用CD 34、CD 38和c-kit分离干细胞。将这些细胞引入急性肝损伤后的NOD/SCID小鼠中，并使用人白蛋白mRNA作为标记物评估转分化为肝细胞。结果，CD 34阳性细胞含有许多肝祖细胞，并且CD 34阳性、CD 38阳性细胞和CD-34阳性、CD-38阴性细胞的转分化时间不同。CIDT不是分离肝祖细胞的有用标记。Fish法证实人脐血细胞与小鼠肝细胞的融合细胞和脐血细胞向肝细胞的转分化细胞均存在。重要的是，两种细胞都表达人白蛋白。这些结果表明，肝细胞样细胞由经转分化的肝细胞和脐带血细胞与肝细胞的融合细胞组成。