Final Report Summary - INDUVIR (Improved gene transfer system to iPS cells in mouse)
The scientific aim of INDUVIR was to improve the current knowledge on the generation, maintenance and characteristics of induced pluripotent stem (iPS) cells and on their differentiation toward specific, especially cardiac lineages. We have investigated methods for safer and more efficient ways to de-differentiate adult mouse cells to a pluripotent stage. We have tested novel gene delivery systems to minimise the risk of insertional mutagenesis caused by multiple insertion sites and developed techniques to remove the integrated transgenes from the genome. We have also developed methods for targeted differentiation of the iPS cells to cardiac cells. These new techniques make iPS cells potentially more suitable for applications in the biomedical area, developing novel drug testing methods and animal model test systems for regenerative stem cell therapy.
IPS cells differentiated into cardiac and neuronal cell types can also serve as useful tools for pharmacological studies or high-throughput screening. The information generated by these studies will contribute to stem cell therapy and modern regenerative medicine.
The objectives of the project were to generate iPS cells by minimal integration sites using a lentiviral technology and to characterise the generated iPS cell lines in vitro. We achieved all these goals as it was planned originally. We prepared excisable lentiviral vectors having the four reprogramming factors in a policystronic cassette. We generated mouse iPS cells by viral and non-viral (transposone based) reprogramming from three different genetic backgrounds. We characterised all of our iPS cells and showed that these cells behave like ES cells in pluripotency assays. We were able to excise the reprogramming cassette from the iPS cells reprogrammed by lentiviral construct.
The ageing European population is prone to various diseases, causing immense societal and economic problems. Cell therapy, tissue engineering and regenerative medicine are amongst the most promising technologies for the treatment of heart diseases, diabetes and broad range of neurological disorders. One of the potential treatments of these diseases could be the use of tissue engineering with stem cells. Many attempts have been made to regenerate damaged tissues by cell therapy, but the best source of stem cells is not known yet.
The iPS technology would potentially allow generating patient and disease specific stem cells and derivates, yet it would lack many of the technical, ethical and legal issues associated with human ES cell research including therapeutic cloning. Also by using patient specific / autologous cells we can prevent the rejection the implanted cells or tissues. Despite many optimistic predictions, the generation of safe and efficient cells for therapy is more difficult than expected. Current methods for generation of iPS cells carry a possible danger of malignant transformation caused by insertional mutagenesis. Another challenging task is the well-controlled and efficient differentiation of iPS cells to specific lineages, which can efficiently engraft the damaged tissue. The techniques developed in our study on a mouse model have the potential to generate therapeutically safer iPS cells thus bringing potential medical applications closer to implementation and making them less ethically sensitive and more socially acceptable.
Contact details
Scientist in charge:
Prof. Andras Dinnyes
BioTalentum Ltd
2100 Godollo, Aulich Lajos u.26.
Hungary
Tel: +36-205-109632
Email address: andras.dinnyes@biotalentum.hu
IPS cells differentiated into cardiac and neuronal cell types can also serve as useful tools for pharmacological studies or high-throughput screening. The information generated by these studies will contribute to stem cell therapy and modern regenerative medicine.
The objectives of the project were to generate iPS cells by minimal integration sites using a lentiviral technology and to characterise the generated iPS cell lines in vitro. We achieved all these goals as it was planned originally. We prepared excisable lentiviral vectors having the four reprogramming factors in a policystronic cassette. We generated mouse iPS cells by viral and non-viral (transposone based) reprogramming from three different genetic backgrounds. We characterised all of our iPS cells and showed that these cells behave like ES cells in pluripotency assays. We were able to excise the reprogramming cassette from the iPS cells reprogrammed by lentiviral construct.
The ageing European population is prone to various diseases, causing immense societal and economic problems. Cell therapy, tissue engineering and regenerative medicine are amongst the most promising technologies for the treatment of heart diseases, diabetes and broad range of neurological disorders. One of the potential treatments of these diseases could be the use of tissue engineering with stem cells. Many attempts have been made to regenerate damaged tissues by cell therapy, but the best source of stem cells is not known yet.
The iPS technology would potentially allow generating patient and disease specific stem cells and derivates, yet it would lack many of the technical, ethical and legal issues associated with human ES cell research including therapeutic cloning. Also by using patient specific / autologous cells we can prevent the rejection the implanted cells or tissues. Despite many optimistic predictions, the generation of safe and efficient cells for therapy is more difficult than expected. Current methods for generation of iPS cells carry a possible danger of malignant transformation caused by insertional mutagenesis. Another challenging task is the well-controlled and efficient differentiation of iPS cells to specific lineages, which can efficiently engraft the damaged tissue. The techniques developed in our study on a mouse model have the potential to generate therapeutically safer iPS cells thus bringing potential medical applications closer to implementation and making them less ethically sensitive and more socially acceptable.
Contact details
Scientist in charge:
Prof. Andras Dinnyes
BioTalentum Ltd
2100 Godollo, Aulich Lajos u.26.
Hungary
Tel: +36-205-109632
Email address: andras.dinnyes@biotalentum.hu