Objective Liver diseases are becoming one of the most common causes of mortality in developing countries, and orthotopic liver transplantation is the only available treatment. However, this procedure carries implies indefinite immunosupression treatment associated with heavy side effects and eventual rejection. Furthermore, an increasing number of patients die while on the liver transplant waiting list due to the shortage of donor livers. Hepatocyte transplantation recently became an alternative to transplantation for the treatment of life-threatening Ineherithed Metabolic Diseases (IMDs) of the liver. However, this approach is also hampered by the lack of donors and by the difficulty in expending hepatocytes in vitro. Therefore, developing alternative source of hepatocytes represents a major challenge for the regenerative medicine field. Pluripotent stem cells generated from reprogrammed somatic cells (human Induced Pluripotent Stem Cells or hIPSCs) represent an advantageous solution since they can proliferate indefinitely in vitro while maintaining their capacity to differentiate into a broad number of cell types including hepatocytes. In addition, hIPSCs could enable the production of patient specific cells fully immuno-compatible with the original donor thereby avoiding the need for immune suppressive treatment. Here, we propose to systematically address the limitations preventing the use of hIPSCs for cells based therapy of IMDs. We will first develop novel methods to generate “better” hIPSCs fully compatible with clinical applications and to differentiate them into adult hepatocyes. In parallel, we will establish a novel approach for editing the mammalian genome and to correct the genetic defects associated with IMDs. Finally, we will validate the safety and the functionality of hIPSCs derived hepatocytes in vivo. Overall this comprehensive study will aim to provide the first proof of principle that hIPSCs could be useful in novel therapies against IMDs. Fields of science social sciencessociologydemographymortalitymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinehepatologymedical and health sciencesclinical medicinetransplantationnatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Address Trinity lane the old schools CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Ludovic Patrick Vallier (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 1 500 000,00 Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom EU contribution € 1 500 000,00 Address Trinity lane the old schools CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Ludovic Patrick Vallier (Dr.) Links Contact the organisation Opens in new window Website Opens in new window
