iPS-technology and patient specific disease models

iPS技术的开发和应用有望彻底改变对疾病的理解和治疗，因为对患者特异性iPS细胞进行重编程的能力允许创建基于细胞的疾病模型，其中以前极难获得足够量的相关人类细胞类型，包括心肌细胞、内皮细胞和血管平滑肌细胞，探索心血管疾病的潜在机制。我们已经成功地从健康志愿者和患者中产生了几种人iPS细胞系。迄今为止，这些患者特异性细胞系包括乔布斯综合症、CADASIL、DADA 2、特纳综合症和Degos患者，仅举几例。我们已经成功地使用慢病毒和逆转录病毒递送四种必需的多能因子，并且还广泛地表征了所产生的许多人iPS细胞系。我们的iPS细胞系表现出人类胚胎干细胞（ESC）的特征，包括形成胚状体的能力。这些细胞还表达高水平的碱性磷酸酶，Oct 4和Nanog，以及人ESC标志物SSEA 4和Tra-1-60。此外，我们已经证实，这些细胞表现出正常的核型，并开发了用于将这些iPS细胞分化为各种外胚层、中胚层和内胚层谱系的方案，如通过巢蛋白、Runx 1和GATA 4的各自表达所评估的。已经实现了iPS细胞向与心血管疾病相关的谱系（包括内皮细胞和平滑肌细胞）的成功分化，并且我们正在继续将它们应用于我们研究的疾病的体外模型中。

The development and application of iPS technology promises to revolutionize the understanding and treatment of disease, as the ability to reprogram patient specific iPS cells permit the creation of cell-based disease models where it has previously been extremely difficult to obtain sufficient amounts of the relevant human cell types, including cardiac myocytes, endothelial cells and vascular smooth muscle cells, to explore the mechanisms underlying cardiovascular diseases. We have successfully generated several human iPS cell lines from both healthy volunteers and patients. To date, these patient specific cell lines have included individuals with Jobs syndrome, CADASIL, DADA2, Turner Syndrome and Degos just to name a few. We have been successful using both lentiviral and retroviral delivery of the four requisite pluripotent factors and have also extensively characterized many of the human iPS cell lines generated. Our iPS cell lines exhibit characteristics of human embryonic stem cells (ESC) including the ability to form embroid bodies. These cells also express high levels of alkaline phosphatase, Oct4 and Nanog, as well as the human ESC markers SSEA4 and Tra-1-60. Furthermore, we have confirmed that these cells manifest a normal karyotype and have developed protocols for differentiation of these iPS cells down various ectodermal, mesodermal and endodermal lineages as assessed by the respective expression of Nestin, Runx1 and GATA4. Successful differentiation of iPS cells towards lineages that are relevant for cardiovascular disease, including endothelial and smooth muscle cells, has been achieved and we are continuing to apply them in in vitro models of diseases that we investigate.