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In Vivo Expansion of Human Hepatocytes in FRG Mice

FRG 小鼠体内人肝细胞的扩增

基本信息

批准号：
8290314
负责人：
Markus Grompe
金额：
$ 31.79万
依托单位：
YECURIS CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-15 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8290314
关键词：
Animals Cancer Biology Cell Death Cells Communicable Diseases Cryopreservation Cytochrome P450 Enzyme Induction Enzymes Excision Farming environment Freezing Frequencies Future Gene Expression Goals Health Hepatocyte Human Immune In Vitro Liver Marketing Measurement Measures Medicine Methods Modeling Molecular Profiling Mus Operative Surgical Procedures Pathway interactions Peptide Hydrolases Perfusion Pharmacologic Substance Phase Preclinical Drug Development Price Production Property RNA Sequences Regimen Research Research Personnel Resources Sampling Small Business Technology Transfer Research Solutions Source Specimen System Technology Temperature Testing Toxicology Transplantation Tyrosine base commercial application cost cost effective design drug development drug metabolism drug testing genetic selection improved in vitro testing in vivo indexing liver transplantation mRNA Expression metabolic abnormality assessment pre-clinical success

项目摘要

DESCRIPTION (provided by applicant): The FDA requires the use of human hepatocytes for preclinical drug testing by pharmaceutical researchers, but unfortunately the supply of these cells is severely limited. Currently, cadaveric donors and surgical liver resection specimens are currently the only available source of human hepatocytes. These samples are very scarce and often yield cells of poor quality unsuitable for research. We have developed technology to massively expand fully functional primary human hepatocytes by serial transplantation in immune deficient FRGN mice in vivo. Hepatocytes isolated from these animals are highly viable and functional. Cell farming in FRGN mice allows the production of an unlimited supply of human hepatocytes for research in toxicology, drug metabolism, infectious disease, and cancer biology. The aims of this application are to optimize the isolation and storage of farmed hepatocytes and to fully validate their utility in comparison to the currently available cells. Once fully validated, these cells are going to be valuable in the commercial market.

描述(申请人提供)：FDA要求制药研究人员使用人类肝细胞进行临床前药物测试，但不幸的是，这些细胞的供应严重有限。目前，身体供体和外科手术切除的肝标本是目前唯一可用的人类肝细胞来源。这些样本非常稀缺，而且经常产生质量不佳的细胞，不适合研究。我们已经开发了一种技术，通过在体内免疫缺陷的FRGN小鼠体内进行连续移植来大规模扩增具有全功能的原代人肝细胞。从这些动物中分离出的肝细胞具有很高的活性和功能。在FRGN小鼠中进行细胞培养，可以生产出无限供应的人类肝细胞，用于毒理学、药物代谢、传染病和癌症生物学的研究。这项应用的目的是优化培养肝细胞的分离和保存，并与目前可用的细胞进行比较，充分验证它们的实用性。一旦完全验证，这些细胞将在商业市场上具有价值。