Core--Human ES Cell Targeting

核心--人ES细胞靶向

• 批准号: 6960863
• 负责人: ROGER A WILLIAMSON
• 金额: $ 18.63万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6960863
• 关键词: biomedical facility; biotechnology; cooperative study; gene targeting; human embryonic stem cell line; muscular dystrophy; musculoskeletal disorder therapy; therapy design /development; tissue resource /registry

The isolation of human embryonic stem (ES) cells has fostered development of a potent area of investigation which will impact our understanding of disease mechanisms and has potential to yield effective therapies. These pathogenetic insights and possible treatments may be applied to the various types of muscular dystrophy. This proposal has as its goal the establishment of a Core Facility which will serve as a resource for investigators seeking the causes and cures for these diseases. Two primary services will be offered by this Core: 1) targeting or inactivating genes in human ES cells which cause various forms of muscular dystrophy and 2) in vitro differentiation of these gene targeted cell lines along the skeleteal muscle lineage pathway. Cardiac muscle could also be differentiated. Proof-of-principle experiments will initially target the genes which cause limb-girdle muscular dystrophy 2I (LGMD2I) and fascioscapulohumeral muscular dystrophy (FSHD). Protocols to differentiate skeletal muscle and its precursors will be developed coincident with the gene targeting studies. These latter studies will take advantage of embryoid bodies, derived from cultured human ES cells, which form tissues from all three germ layers. Revealing studies will become possible when gene targeting of muscular dystrophy genes is combined with in vitro differentiation of these cell lines. The ultimate goal of this approach is the provision of cell-based models of disease for development of therapies directed against the diverse forms of muscular dystrophy. The Core Facility proposed herein is envisioned to be a resource which may be utilized by investigators across the country.

人类胚胎干细胞的分离促进了有效的研究领域的发展，这将影响我们对疾病机制的理解，并具有产生有效疗法的潜力。这些致病的见解和可能的治疗方法可以应用于各种类型的肌肉营养不良。该提案的目标是建立核心设施，该设施将作为寻求这些疾病原因和治愈的调查人员的资源。该核心将提供两种主要服务：1）在人ES细胞中靶向或灭活基因，这些基因引起各种形式的肌肉营养不良，2）沿Skeleteal Muscle seleage途径的这些基因靶向细胞系的体外分化。心肌也可以区分。原理证明实验最初将针对 引起肢体肌营养不良2i（LGMD2I）和fassioscapulohumeral肌肉营养不良（FSHD）的基因。区分骨骼肌及其前体的方案将与基因靶向研究相吻合。这些后者的研究将利用源自培养的人类ES细胞的胚胎体，这些胚胎从所有三个细菌层中形成组织。当将肌肉营养不良基因的基因靶向与这些细胞系的体外分化相结合时，将成为可能的研究。这种方法的最终目的是提供基于细胞的疾病模型，用于开发针对肌肉营养不良的各种形式的疗法。本文提议的核心设施被设想为全国调查人员可以利用的资源。