In Vivo Expansion of Human Hepatocytes in FRG Mice

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。

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.