Innovative strategies to generate human hepatocytes for treatment of metabolic Liver diseases: Tools for personalized cell therapy
|Title||Innovative strategies to generate human hepatocytes for treatment of metabolic Liver diseases: Tools for personalized cell therapy|
|Sponsor||European Union's Seventh Framework Programme (FP7)|
Associated cell lines
Transplantation of donor hepatocytes has become an alternative to liver transplantation for the treatment of liver diseases. However, in addition to the complication imposed by severe shortage of donor livers, adult hepatocytes cannot be expanded in vitro. Autologous transplantation of genetically corrected hepatocytes represents another strategy as it circumvents the need for immunosuppression but this approach requires removal of 20% of the liver to isolate hepatocytes, which is not devoid of risks in patients with metabolic diseases. Therefore, there is a critical need to explore the potential human stem cells such as human Embryonic Stem (hES) cells to generate sufficient quantities of functional human hepatocytes. However, the production of safe and fully functional, human hepatocytes from hES cells under GMP conditions for clinical applications remains to be achieved. The general scientific objectives of this proposal are: - to develop scale-up procedures for hES cells and to produce GMP-grade tissue culture reagents that will facilitate large-scale differentiation of hES cells to hepatocytes. InnovaLiv aims to provide the EU healthcare system with a renewable and reliable source of functional clinical-grade hepatocytes generated from EU hES cells lines. Rigorous standards to ensure the safety and quality of these cells will be developed. The GMP-compliant hepatocytes will be prepared as a prototype therapy aiming at treating one patient on the basis of a compasive use protocol. - to provide proof-of-principle that defective hepatic function associated with inherited disorders (Familial Hypercholesterolemia, Hemophilia B, Crigler-Najjar) can be regenerated by correction of the deficiency in patient-specific iPS cells using integration-targeted lentiviral vectors to express the therapeutic cDNAs. Commercialization of novel products such as GMP-grade cells and cell culture tools will be performed by two partner SMEs that will assume leading roles in InnovaLiv.