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.

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National Heart, Lung, and Blood Institute
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Efthymiou, Anastasia G; Chen, Guibin; Rao, Mahendra et al. (2014) Self-renewal and cell lineage differentiation strategies in human embryonic stem cells and induced pluripotent stem cells. Expert Opin Biol Ther 14:1333-44
Negro, Alejandra; Boehm, Manfred (2014) Cardiomyocyte maturation: It takes a village to raise a kid. J Mol Cell Cardiol 74:193-5
Sangaré, Modibo; Hendrickson, Brant; Sango, Hammadoun Ali et al. (2014) Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa. Ann Neurol 75:525-32
Grunseich, Christopher; Zukosky, Kristen; Kats, Ilona R et al. (2014) Stem cell-derived motor neurons from spinal and bulbar muscular atrophy patients. Neurobiol Dis 70:12-20
Michelis, Katherine C; Boehm, Manfred; Kovacic, Jason C (2014) New vessel formation in the context of cardiomyocyte regeneration--the role and importance of an adequate perfusing vasculature. Stem Cell Res 13:666-82