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Generation of induced pluripotent stem cells-derived hepatocyte-like cells for ex vivo gene therapy of primary hyperoxaluria type 1

dc.rights.licenseopenen_US
dc.contributor.authorESTEVE, J.
dc.contributor.authorBLOUIN, J. M.
dc.contributor.authorLALANNE, M.
dc.contributor.authorAZZI-MARTIN, L.
dc.contributor.authorDUBUS, Pierre
dc.contributor.authorBIDET, A.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorHARAMBAT, Jerome
IDREF: 110567358
dc.contributor.authorLLANAS, B.
dc.contributor.authorMORANVILLIER, Isabelle
dc.contributor.authorBEDEL, Aurelie
dc.contributor.authorMOREAU-GAUDRY, Francois
dc.contributor.authorRICHARD, Emmanuel
dc.date.accessioned2020-06-08T11:37:21Z
dc.date.available2020-06-08T11:37:21Z
dc.date.issued2019-05-21
dc.identifier.issn1873-5061en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/7809
dc.description.abstractEnPrimary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of the liver metabolism due to functional deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in overproduction of oxalate which complexes with calcium to form insoluble calcium-oxalate salts in urinary tracts, ultimately leading to end-stage renal disease. Currently, the only curative treatment for PH1 is combined liver-kidney transplantation, which is limited by donor organ shortage and lifelong requirement for immunosuppression. Transplantation of genetically modified autologous hepatocytes is an attractive therapeutic option for PH1. However, the use of fresh primary hepatocytes suffers from limitations such as organ availability, insufficient cell proliferation, loss of function, and the risk of immune rejection. We developed patient-specific induced pluripotent stem cells (PH1-iPSCs) free of reprogramming factors as a source of renewable and genetically defined autologous PH1-hepatocytes. We then investigated additive gene therapy using a lentiviral vector encoding wild-type AGT under the control of the liver-specific transthyretin promoter. Genetically modified PH1-iPSCs successfully provided hepatocyte-like cells (HLCs) that exhibited significant AGT expression at both RNA and protein levels after liver-specific differentiation process. These results pave the way for cell-based therapy of PH1 by transplantation of genetically modified autologous HLCs derived from patient-specific iPSCs.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.enLEHA
dc.title.enGeneration of induced pluripotent stem cells-derived hepatocyte-like cells for ex vivo gene therapy of primary hyperoxaluria type 1
dc.title.alternativeStem Cell Resen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.scr.2019.101467en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed31151050en_US
bordeaux.journalStem Cell Researchen_US
bordeaux.page101467en_US
bordeaux.volume38en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamLEHA_BPH
bordeaux.teamLEHA_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03209536
hal.version1
hal.date.transferred2021-04-27T09:46:10Z
hal.exporttrue
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