Cel "Bile synthesis and secretion are crucial to liver function and involve multiple proteins. Disorders due to defects in this process (Inherited Cholestatic Disorders, ICDs) lead to progressive liver disease. Many ICD patients do not respond to medical treatment and need liver transplantation (LT). Although ICDs are rare, multifactorial cholestatic diseases are common and many patients will benefit from ICD research.There is acute shortage of liver donors. 10% of patients die while waiting on the liver transplant list. Therefore alternatives to LT are urgently needed. Bioengineered tissues may reduce the need for donor organs but complexity of it's organisation makes generation of functional liver challenging.The OBJECTIVE of this project is to generate Cultured Liver Organoids (CLOs) using hepatocytes cultured on 3-D scaffolds as novel models for study of liver development and disease and potential treatment of ICDs.3-D extracellular matrix (ECM) scaffolds derived from decellularised livers and polymeric matrices (PM) have been used to mimic liver architecture but further work is needed to establish functional bile flow.Human Induced Pluripotent Stem Cells (hIPSCs) derived from reprogrammed skin fibroblasts by overexpression of pluripotency factors can proliferate and be differentiated into various cell types including hepatocytes. hIPSCs enable production of patient specific cells, which are fully immuno-compatible. Genetically corrected mutant hIPSCs differentiated into hepatocytes have been used as cell therapy in animal models of inherited metabolic disorders but direct infusion of hepatocytes into the liver is unlikely to achieve polarised bile flow and correct ICDs.Therefore hIPSCs developed from ICD patients will be used to culture hepatocytes on decellularised mouse liver ECM to generate in vitro models of ICDs. CLOs containing hepatocytes from genetically corrected hIPSC will be tested in mouse models of ICDs as potential treatment." Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinehepatologymedical and health sciencesclinical medicinetransplantation Program(-y) 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) Temat(-y) 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. Zaproszenie do składania wniosków ERC-2013-StG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca UNIVERSITY COLLEGE LONDON Wkład UE € 1 500 000,00 Adres GOWER STREET WC1E 6BT LONDON Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Daniele Giannone (Mr.) Kierownik naukowy Paul Gissen (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITY COLLEGE LONDON Wkład UE € 1 500 000,00 Adres GOWER STREET WC1E 6BT LONDON Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Daniele Giannone (Mr.) Kierownik naukowy Paul Gissen (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych