Development of humanized models using human induced pluripotent stem cells

使用人类诱导多能干细胞开发人源化模型

• 批准号: 7852256
• 负责人: JOHN K. CRITSER
• 金额: $ 105.7万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7852256
• 关键词: Animal Model; Animals; Biological Assay; Blood; Cardiovascular Diseases; Cell Line; Cells; Chimera organism; Dental Pulp; Development; Diabetes Mellitus; Diphtheria Toxin; Disease; Dose; Drug Controls; Embryo; Embryo Transfer; Embryonic Development; Endothelium; Enhancers; Environment; Family suidae; Ganciclovir; Genes; Genetic; Genetic Recombination; Genotype; Goals; Health; Hematopoietic; Hematopoietic System; Herpesviridae; Homozygote; Human; In Vitro; Methods; Modeling; Multipotent Stem Cells; Mus; Organ; Pathology; Pharmaceutical Preparations; Phenotype; Prevention; Reporting; Source; Stem cells; System; Tamoxifen; Thymidine Kinase; Time; Tissue-Specific Gene Expression; Tissues; Transgenic Mice; Vascular Endothelium; Xenograft procedure; blastocyst; cancer therapy; clinical application; embryo/fetus; embryonic stem cell; hematopoietic tissue; high risk; human disease; induced pluripotent stem cell; innovation; killings; leukemia/lymphoma; mouse model; novel; pathogen; preclinical study; programs; promoter; public health relevance; recombinase; stem; suicide gene; tool; vaccine development

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.

描述（由申请人提供）：该项目的目标是开发一种小鼠-人类嵌合模型，该模型具有源自人类诱导多能干（iPS）细胞的血管内皮和造血系统，而所有其他组织和器官均来自小鼠。先前的报告已经证明，制造小鼠-人类嵌合体是可能的，并且人类多能和专能干细胞能够在发育过程中对小鼠胚胎环境的空间和时间程序做出反应。我们相信这是一项高度创新、高风险的提案，对广泛的转化和临床应用具有潜在的巨大影响。例如，小型动物-人类嵌合模型（例如小鼠）在以下研究中非常有价值：（a）白血病和淋巴瘤； (b) 心血管疾病； (c) 血源性传染性病原体； (d) 疫苗开发； (e) 造血系统病理学。 公共健康相关性：该项目的目标是开发一种新型动物模型，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。该模型将对广泛的转化和临床应用产生巨大影响。