Your browser doesn't support javascript.
loading
Coculture model of a liver sinusoidal endothelial cell barrier and HepG2/C3a spheroids-on-chip in an advanced fluidic platform.
Messelmani, Taha; Le Goff, Anne; Soncin, Fabrice; Souguir, Zied; Merlier, Franck; Maubon, Nathalie; Legallais, Cécile; Leclerc, Eric; Jellali, Rachid.
Afiliação
  • Messelmani T; Université de Technologie de Compiègne, CNRS, Biomechanics and Bioengineering, Centre de Recherche Royallieu, CS 60319, 60203 Compiègne Cedex, France.
  • Le Goff A; Université de Technologie de Compiègne, CNRS, Biomechanics and Bioengineering, Centre de Recherche Royallieu, CS 60319, 60203 Compiègne Cedex, France.
  • Soncin F; CNRS/IIS/Centre Oscar Lambret/Lille University SMMiL-E Project, CNRS Délégation Hauts-de-France, 43 Avenue le Corbusier, 59800 Lille, France; CNRS, IRL2820, Laboratory for Integrated Micro Mechatronic Systems, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8
  • Souguir Z; HCS Pharma, 250 rue Salvador Allende, Biocentre Fleming Bâtiment A, 59120 Loos, France.
  • Merlier F; Université de Technologie de Compiègne, UPJV, CNRS, Enzyme and Cell Engineering, Centre de Recherche Royallieu, Cedex CS 60319, 60203 Compiègne, France.
  • Maubon N; HCS Pharma, 250 rue Salvador Allende, Biocentre Fleming Bâtiment A, 59120 Loos, France.
  • Legallais C; Université de Technologie de Compiègne, CNRS, Biomechanics and Bioengineering, Centre de Recherche Royallieu, CS 60319, 60203 Compiègne Cedex, France.
  • Leclerc E; Université de Technologie de Compiègne, CNRS, Biomechanics and Bioengineering, Centre de Recherche Royallieu, CS 60319, 60203 Compiègne Cedex, France; CNRS, IRL2820, Laboratory for Integrated Micro Mechatronic Systems, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, To
  • Jellali R; Université de Technologie de Compiègne, CNRS, Biomechanics and Bioengineering, Centre de Recherche Royallieu, CS 60319, 60203 Compiègne Cedex, France. Electronic address: rachid.jellali@utc.fr.
J Biosci Bioeng ; 137(1): 64-75, 2024 Jan.
Article em En | MEDLINE | ID: mdl-37973520
The liver is one of the main organs involved in the metabolism of xenobiotics and a key organ in toxicity studies. Prior to accessing the hepatocytes, xenobiotics pass through the hepatic sinusoid formed by liver sinusoidal endothelial cells (LSECs). The LSECs barrier regulates the kinetics and concentrations of the xenobiotics before their metabolic processing by the hepatocytes. To mimic this physiological situation, we developed an in vitro model reproducing an LSECs barrier in coculture with a hepatocyte biochip, using a fluidic platform. This technology made dynamic coculture and tissue crosstalk possible. SK-HEP-1 and HepG2/C3a cells were used as LSECs and as hepatocyte models, respectively. We confirmed the LSECs phenotype by measuring PECAM-1 and stabilin-2 expression levels and the barrier's permeability/transport properties with various molecules. The tightness of the SK-HEP-1 barrier was enhanced in the dynamic coculture. The morphology, albumin secretion, and gene expression levels of markers of HepG2/C3a were not modified by coculture with the LSECs barrier. Using acetaminophen, a well-known hepatotoxic drug, to study tissue crosstalk, there was a reduction in the expression levels of the LSECs markers stabilin-2 and PECAM-1, and a modification of those of CLEC4M and KDR. No HepG2/C3a toxicity was observed. The metabolisation of acetaminophen by HepG2/C3a monocultures and cocultures was confirmed. Although primary cells are required to propose a fully relevant model, the present approach highlights the potential of our system for investigating xenobiotic metabolism and toxicity.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Endoteliais / Acetaminofen Idioma: En Revista: J Biosci Bioeng Assunto da revista: ENGENHARIA BIOMEDICA / MICROBIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Endoteliais / Acetaminofen Idioma: En Revista: J Biosci Bioeng Assunto da revista: ENGENHARIA BIOMEDICA / MICROBIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França