In Vivo Expansion of Human Hepatocytes in FRG Mice

FRG 小鼠体内人肝细胞的扩增

• 批准号: 8124068
• 负责人: Markus Grompe
• 金额: $ 45.57万
• 依托单位: YECURIS CORPORATION
• 依托单位国家: 美国
• 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/8124068
• 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

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. PUBLIC HEALTH RELEVANCE: The successful implementation of human hepatocyte farming technology will significantly impact human health by providing this vital resource for drug development at a higher quality and lower cost than is currently available.

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试验，但不幸的是，这些细胞的供应严重有限。目前，尸体供体和手术肝切除标本是目前唯一可用的人类肝细胞来源。这些样本非常稀少，而且通常产生的细胞质量很差，不适合研究。我们已经开发出一种技术，通过在免疫缺陷的FRGN小鼠体内进行连续移植，大规模扩增全功能的人肝细胞。从这些动物中分离的肝细胞具有很高的活力和功能。FRGN小鼠的细胞养殖可以为毒理学、药物代谢、传染病和癌症生物学的研究提供无限的人类肝细胞。本应用程序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。一旦完全验证，这些电池将在商业市场上具有价值。