Better ways to make Induced Pluripotential Stem (iPS) Cells

诱导多能干细胞（IPS细胞）有望彻底改变肌肉疾病的研究。iPS细胞， 通过将转录因子引入原代细胞培养物中而产生，类似于胚胎干细胞，并且可以 用于研究发育机制，疾病状态的变化，并调查其影响 药物来纠正缺陷。我们在这项提案中的科学目标是开发快速创造 非遗传修饰的iPS细胞来自选定的患有确定的肌肉疾病的患者。成功与这些 这些方法将提高从特定疾病成纤维细胞产生iPS细胞的效率和有效性 保存在Clinical Repository Research Core中。这些将用于研究发育病理学 这些肌肉疾病的研究，并为未来的细胞治疗应用奠定基础。表型的一个要素 细胞分化过程中的表征将使用力评估研究核心来确定 与治疗的野生型细胞相比，鉴定的肌肉疾病突变是否改变了力的产生 同样的。该提案的具体目标是： 具体目的1：使用非整合病毒载体制备iPS细胞。工作假设是， 不需要整合到基因组中来实现iPS表型的重编程。 具体目标2：在制备iPS细胞中替代危险性较低的组分。工作 一种假说是，需要染色质开放，而不是致癌转化， 重编程为iPS表型。

Induced pluripotent stem cells (IPS cells) promise to revolutionize the study of muscle disease. iPS cells, made by introducing transcription factors into primary cell cultures, resemble embryonic stem cells, and can be used to study developmental mechanisms, their alteration in disease states, and to investigate the effects of drugs to correct the defect. Our scientific goal in this proposal is to develop methods for rapid creation of non-genetically modified iPS cells from selected patients with identified muscle disease. Success with these methods will improve efficiency and effectiveness of generation of iPS cells from specific disease fibroblasts maintained in Clinical Repository Research Core. These will be used to study the developmental pathology of these muscle diseases and to lay the basis for future cell therapy applications. An element of phenotypic characterization of the cells during differentiation will use the Force Assessment Research Core to determine whether identified muscle disease mutations alter force generation compared to wild type cells treated similarly. Specific Aims of the proposal are: Specific aim 1: To prepare iPS cells using a non-integrating viral vector. The working hypothesis is that integration into the genome is not required to bring about reprogramming to the iPS phenotype. Specific aim 2: To substitute less hazardous components in the preparation of iPS cells. The working hypothesis is that chromatin opening, rather than oncogenic transformation, is required to enable reprogramming to the iPS phenotype.