Final Report Summary - INDUHEART (Induced pluripotent stem cells for cardiomyocyte generation in mouse) The scientific aim of the InduHeart project was to generate new comparative information on the generation, maintenance, characteristics of induced Pluripotent Stem (iPS) cells in mouse and on their differentiation towards the cardiac lineage. The main scientific goals of the project: Generation of mouse iPS cells by a novel transposon-mediated gene transfer Characterisation of transposon-derived iPS cells In vitro differentiation of ES and iPS cell lines towards cardiac cell lineage.We have generated a system for the efficient reprogramming of mouse somatic cells utilising a transposon expressing a stem cell cassette. Following the completion of reprogramming, the vector were excised from the resulting iPS cells via transient expression of Cre recombinase, generating iPS cells free of residual reprogramming transgenes. As a result, we have generated multiple iPS cell lines from 3 different mouse genetic background. The cell lines have been characterised and have shown features of pluripotent stem cells by their gene expression patterns and protein expression as detected by immunohistochemistry. The novel iPS cell lines have been used to generate embryoid bodies (EBs) in a bioreactor system with excellent results compared to hanging drop and aggregation methods of EB production. Differentiation of the iPS cells towards cardiac cells has been successful.The iPS method would potentially allow generating patient and disease specific stem cells and derivatives, yet it would lack many of the technical, ethical and legal complications associated with human ES cell research including "therapeutic cloning". It would also accelerate patient and disease specific drug screening. The ultimate goal of somatic reprogramming, thus iPS technology, is to generate functional cell types relevant for therapy such as cardiomyocytes, neurons or insulin-producing cells in vitro. The long-term goal is to create patient-specific donor cells for transplantation therapy. This way the use of autologous cells prevents rejection, and thus the deleterious side effects of immunosuppressive medications can be avoided.Overall, the results of InduHeart in a mouse model are pawing the way towards a safer and more efficient iPS technology with a major positive potential for the fields of pharmaceutical drug testing, tissue engineering and regenerative medicine.Contact details Scientist-in Charge: Prof Andras Dinnyes, BioTalentum Ltd, 2100 Godollo, Aulich Lajos 26. Hungary. Tel: + 36 20 510 9632, Email address: andras. dinnyes@biotalentum. hu
