Development of humanized models using human induced pluripotent stem cells

描述(申请人提供)：该项目的目标是开发一种具有血管内皮细胞和造血系统的鼠-人嵌合模型，该模型来自人类诱导的多能干细胞，而所有其他组织和器官将来自小鼠。此前的报道表明，制造鼠-人嵌合体是可能的，人类多能和多能干细胞能够对发育过程中小鼠胚胎环境的空间和时间程序做出反应。我们相信，这是一项高度创新、高风险的提案，对广泛的翻译和临床应用具有潜在的高影响。例如，小动物-人嵌合模型(如小鼠)在以下研究中将非常有价值：(A)白血病和淋巴瘤；(B)心血管疾病；(C)血液传播的传染病病原体；(D)疫苗开发；(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，并将允许通过临床前试验更快地开发新药。这一模式将对广泛的翻译和临床应用产生很大影响。

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.