Cutting-Edge Seminar
Speaker: Dr. Jürgen Hescheler （Professor, University of Cologne）
Title: Pluripotent Stem Cells for Cardiovascular Research and Later Clinical Application
Date&Time: 19 Mar. (Wed.) 2014, 12:00-13:00
Venue: Conference Room(1F), IMEG
Abstract:
We culti¬vated embryonic stem (ES) and induced pluripotent stem (iPS) cells in 3-D cell aggregates (embryoid bodies, EBs), where they differentiate into derivatives of all three germ layers. To select only one lineage, e.g. the cardiac lineage, and to allow the identi¬fication of the transplanted cells, transgenic ES cells were used. They contained a vector with a cloning sites for EGFP as well as for an puromycin resistance cassette for selection under the -MHC promoter. We aimed at generating iPS cell-derived cardiomyocytes (CMs) and their molecular and functional charac¬te¬ri¬zation in comparison to CMs derived from established ES cells as well as native CMs from embryos. Besides basic scientific aspects pluripotent stem cells also provide a promising tool for translational applied research. In my presentation
I first will put emphasis on the development of human ES based screening assays to predict toxic effects and to learn about toxicological mechanisms. Secondly, to demon¬strate the ability of ES cells for regenerative medicine and tissue repair, CMs differentiated from ES cells were injected into the cryoinfarcted left ventricular wall of adult wild type mice. Translation from the laboratory into the clinic will be one of the future key problems of stem cell research. Although proof of principle for the therapeutic use of iPS cells in cardiac diseases has been shown both at the laboratory scale and in animal models, the methods used today for generation, cultivation, differentiation and selection are not yet suitable for the clinic. Thirdly, in order to demonstrate the suitability of pluripotent stem cells for novel disease models, reprogramming of fibroblasts from patients with LQT3 or CPVT syndrome by ectopic expression of the transcription factors Oct4, Sox2, c-Myc and Klf4 resulted in generation of iPS cells for disease modelling. This novel approach may also enable patient-specific cell replacement thera¬pies which appears an indispensable prerequisite for a later use in clinics.
