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.
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