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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：
8537528
负责人：
Markus Grompe
金额：
$ 13.54万
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/8537528
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（由申请人提供）：FDA要求制药研究人员使用人肝细胞进行临床前药物测试，但不幸的是，这些细胞的供应受到严重限制。目前，尸体供体和手术肝切除标本是目前唯一可用的人肝细胞来源。这些样本非常稀少，而且往往产生不适合研究的质量差的细胞。我们已经开发了通过在免疫缺陷的FRGN小鼠体内连续移植来大规模扩增全功能原代人肝细胞的技术。从这些动物中分离的肝细胞具有高度活力和功能。在FRGN小鼠中进行细胞培养可以生产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研究。本申请的目的是优化养殖肝细胞的分离和储存，并与目前可用的细胞相比，充分验证其效用。一旦得到充分验证，这些细胞将在商业市场上具有价值。