| Project 18 |
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Derivation of induced pluripotent stem (iPS) cells from rat and development of novel therapeutic strategiesProf. Bader (first supervisor), Dr. Seifert (second supervisor), Dr. Alenina (mentor); The discovery of induced pluripotent stem (iPS) cells by pioneering work of Yamanaka in 2006 opened new opportunities for therapeutic applications of stem cells. However the potential problem of tumor formation upon treatment of patients with these cells is still unsolved, putting the possible usage of such cells in clinic into a question. This PhD thesis aims to generate iPS cells from rat by lentiviral transfection with 4 pluripotency factors Oct4, Klf4, Sox2, and Myc. The stemness of these cells will be proven by in vitro differentiation into different cell types, as well as monitoring the incorporation of iPS cells into embryos upon injection in blastocysts. Moreover, rat models of myocardial infarction, atherosclerosis and irradiated animals will be used for transplantation experiments to access the regenerative capacities of normal and predifferentiated rat iPS cells. In addition to overcome the problem of tumor formation following iPS transplantations novel strategies employing suicidal genes will be developed. The outcome will be monitored by state-of-the-art phenotyping methodology and may form the basis of novel therapeutic strategies. Langenickel T, Buttgereit J, Pagel-Langenickel I, Lindner M, Beuerlein K, Al-Saadi N, Plehm R, Popova E, Tank J, Dietz R, Willenbrock R, Bader M. Cardiac hypertrophy in transgenic rats expressing a dominant negative mutant of the natriuretic peptide receptor B. Proc Natl Acad Sci USA. 2006; 103: 4735-4740 |
