In Vivo Expansion of Human Hepatocytes in FRG Mice

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。 公共卫生相关性：人类肝细胞培养技术的成功实施将通过以比目前更高的质量和更低的成本为药物开发提供这种重要资源来显著影响人类健康。

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.