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Development of novel humanized-mice and application to regenerative medicine

新型人源化小鼠的研制及其在再生医学中的应用

基本信息

批准号：
12357002
负责人：
HATA Jun-ichi
金额：
$ 27.65万
依托单位：
National Research Institute for Child Health and Development (2001-2002)Keio University (2000)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12357002/
关键词：
Regeneration Osteoporisis tumor angiogenesis hetatitis heart muscle bone marrow stroma cell transplantation 骨粗しょう症

项目摘要

Application of cells/tissues obtained from a human as a new therapy for the disease attracts attention. It seems to be logical that cells/tissues obtained from patients are used for therapy because there is not rejection. Therefore it is important that multiply various cells out of a body are induced into certain differentiation via a specific course. For developmental research of new medical material, we examined an introduction of differentiated cells derived from human bone marrow mesenchymal stem cells and inoculation of these human cells into immunodeficiency mice in this study.At first, the differentiation of cardiac muscle cells from human bone marrow mesenchymal stem cells which cells are easy to gather was performed. As a result, the method for differentiation into the cardiac muscle cells from human marrow mesenchymal stem cells was established. These obtained cardiac muscle cells may be useful for treatment of irreversible heart disorder such as myocardial infarction or cardiomyopathy. Furthermore it succeeds that the human cardiac muscle cells were transplanted into hearts of NOD/SCID. This experimental system may be available for preclinical trial of these muscle cells in vivo and evaluation of safety.The translantations of human bone or liver into NOD/SCID mice were examined. As a results, the reproduction of human bone remodeling, hemopoietic cells and blood vessels derived from human bone was observed. Human hepatic tissues also were maintained in murine tissues over 4 months. These humanized mice (SCID-hu) may be available for drug screening, preclinical trials of novel therapies including gene therapy or molecular targeting therapy, or in vivo analysis in molecular pathology.

从人类获取的细胞/组织作为治疗这种疾病的新方法的应用引起了人们的注意。从患者身上获得的细胞/组织用于治疗似乎是合乎逻辑的，因为没有排斥反应。因此，重要的是，通过特定的过程将体内的各种细胞增殖诱导成一定的分化。为了开发新型医用材料，本研究引入了人骨髓间充质干细胞分化细胞，并将其接种到免疫缺陷小鼠体内。首先，对易采集的人骨髓间充质干细胞进行了心肌细胞的诱导分化。建立了人骨髓间充质干细胞向心肌细胞分化的方法。这些获得的心肌细胞可能用于治疗不可逆转的心脏疾病，如心肌梗死或心肌病。此外，成功地将人心肌细胞移植到NOD/SCID大鼠心脏。该实验系统可用于这些肌肉细胞的体内临床前试验和安全性评估。结果：观察了人骨改建、骨造血细胞和骨血管的复制情况。人肝组织在小鼠体内保存4个月以上。这些人源化小鼠(SCID-HU)可用于药物筛选、包括基因治疗或分子靶向治疗在内的新疗法的临床前试验，或用于分子病理学的活体分析。