Development of humanized models using human induced pluripotent stem cells

描述（由申请人提供）：本项目的目标是开发一种小鼠-人嵌合模型，其血管内皮和造血系统来源于人诱导多能干细胞（iPS），而所有其他组织和器官均来自小鼠。先前的报道已经证明，制造小鼠-人嵌合体是可能的，并且人类多能和多能干细胞能够在发育期间对小鼠胚胎环境的空间和时间程序做出反应。我们相信这是一个高度创新、高风险的提议，对广泛的转化和临床应用具有潜在的高影响。例如，小动物-人嵌合模型（例如小鼠）在以下研究中将是极其有价值的：（a）白血病和淋巴瘤;（B）心血管疾病;（c）血液传播的传染性病原体;（d）疫苗开发;和（e）造血系统病理学。 公共卫生相关性：该项目的目标是开发一种新型的动物模型，更好地反映人类疾病状态，并通过临床前试验更快地开发新药。该模型将对广泛的翻译和临床应用产生重大影响。

DESCRIPTION (provided by applicant): The goal of this project is to develop a mouse-human chimeric model with a vascular endothelium and a hematopoietic system derived from human induced pluripotent stem (iPS) cells while all other tissues and organs will be from a mouse. Previous reports have demonstrated that making mouse-human chimeras is possible and that human pluripotent and multipotent stem cells are able to respond to the spatial and temporal program of the mouse embryonic environment during development. We believe this is a highly innovative, high-risk proposal with potential high-impact for a broad spectrum of translational and clinical applications. For example, small animal-human chimeric models (e.g. mouse) would be extremely valuable in studies of: (a) leukemia and lymphoma; (b) cardiovascular disease; (c) blood-borne infectious pathogens; (d) vaccine development; and (e) hematopoietic system pathology. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a new type of animal model which better reflects human disease states and will allow for more rapid development of new drugs through preclinical trials. This model will have high-impact for a broad spectrum of translational and clinical applications.