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The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism.
Lehmann, Vivian; Schene, Imre F; Ardisasmita, Arif I; Liv, Nalan; Veenendaal, Tineke; Klumperman, Judith; van der Doef, Hubert P J; Verkade, Henkjan J; Verstegen, Monique M A; van der Laan, Luc J W; Jans, Judith J M; Verhoeven-Duif, Nanda M; van Hasselt, Peter M; Nieuwenhuis, Edward E S; Spee, Bart; Fuchs, Sabine A.
Afiliação
  • Lehmann V; Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Schene IF; Department of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
  • Ardisasmita AI; Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Liv N; Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Veenendaal T; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Klumperman J; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
  • van der Doef HPJ; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Verkade HJ; Department of Pediatric Gastroenterology, University Medical Center Groningen, Groningen, The Netherlands.
  • Verstegen MMA; Department of Pediatric Gastroenterology, University Medical Center Groningen, Groningen, The Netherlands.
  • van der Laan LJW; Department of Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
  • Jans JJM; Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
  • Verhoeven-Duif NM; Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
  • van Hasselt PM; Department of Metabolic Diagnostics, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Nieuwenhuis EES; Department of Metabolic Diagnostics, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Spee B; Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Fuchs SA; Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
J Inherit Metab Dis ; 45(2): 353-365, 2022 03.
Article em En | MEDLINE | ID: mdl-34671987
ABSTRACT
Inborn errors of metabolism (IEMs) comprise a diverse group of individually rare monogenic disorders that affect metabolic pathways. Mutations lead to enzymatic deficiency or dysfunction, which results in intermediate metabolite accumulation or deficit leading to disease phenotypes. Currently, treatment options for many IEMs are insufficient. Rarity of individual IEMs hampers therapy development and phenotypic and genetic heterogeneity suggest beneficial effects of personalized approaches. Recently, cultures of patient-own liver-derived intrahepatic cholangiocyte organoids (ICOs) have been established. Since most metabolic genes are expressed in the liver, patient-derived ICOs represent exciting possibilities for in vitro modeling and personalized drug testing for IEMs. However, the exact application range of ICOs remains unclear. To address this, we examined which metabolic pathways can be studied with ICOs and what the potential and limitations of patient-derived ICOs are to model metabolic functions. We present functional assays in patient ICOs with defects in branched-chain amino acid metabolism (methylmalonic acidemia), copper metabolism (Wilson disease), and transporter defects (cystic fibrosis). We discuss the broad range of functional assays that can be applied to ICOs, but also address the limitations of these patient-specific cell models. In doing so, we aim to guide the selection of the appropriate cell model for studies of a specific disease or metabolic process.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article