iPS-technology and patient specific disease models

IPS技术的发展和应用有望彻底改变人们对疾病的认识和治疗。特别是，以前很难获得足够数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，以探索心血管疾病的发病机制。因此，重新编程患者特定的iPS细胞以创建基于细胞的疾病模型的能力代表着我们社区的重大和重要的范式转变。 我们成功地建立了30多个人iPS细胞系，其中包括大约10个患者特有的细胞系。到目前为止，这些患者特有的细胞系包括患有乔布斯综合征的人，以及另一种以循环单核细胞缺乏为特征的罕见综合征。我们已经成功地使用慢病毒和逆转录病毒传递四种必需的多能性因子。我们还对许多产生的人类iPS细胞系进行了广泛的鉴定。我们的iPS细胞系表现出人类胚胎干细胞(ESC)的特征，包括形成刺状体的能力。此外，这些细胞表达高水平的碱性磷酸酶、Oct4和Nanog，以及人类ESC标记SSEA4和Tra-1-60。此外，我们已经证实这些细胞表现出正常的核型，并已经开始制定方案，通过Nestin、RUNX1和GATA4的表达来评估这些iPS细胞向不同的外胚层、中胚层和内胚层方向分化。IPS细胞已经成功地分化为与心血管疾病相关的谱系，包括内皮细胞。

The development and application of iPS technology promises to revolutionize the understanding and treatment of disease. In particular, 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. As such, the ability to reprogram patient specific iPS cells to create cell based disease models represents a major and important paradigm shift for our community. We successfully generated in excess of 30 human iPS cell lines, including approximately 10 patient specific cell lines. To date, these patient specific cell lines have included individuals with Jobs syndrome, as well as an additional rare syndrome characterized by a circulating monocyte deficiency. We have been successful using both lentiviral and retroviral delivery of the four requisite pluripotent factors. We 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. In addition, these cells 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 karyotyp and have already begun to develop 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 cells, has already been achieved.