Sponsored Content by CN-BioMay 10 2024Reviewed by Aimee Molineux The connection between the human liver and the intestine is unique, and the “gut-liver axis” plays a vital role in regulating liver disease pathology.
The presently available preclinical models of MASLD and MASH, whether in vivo or in vitro, have several limitations and do not fully represent the important aspects of the human disease state.3 The cells were co-cultured at physiologically pertinent ratios in the PhysioMimix® Multi-organ System for up to 15 days. Fat accumulation was assessed by Oil Red O staining of fixed microtissues and then normalized to the total protein content.
CYP activity and drug metabolism data were produced through quantitative LC-MS analysis. TEER values were measured using an EVOM2 probe .Figure 1. Liver MPS and intestine liver MPS set up. A) Liver MPS designed for PhysioMimix® OOC system, uses open well plates for the culture of primary liver cells in a 3D engineered scaffold, with 12 replicates per plate. Schematic representation of each replicate shown.
Figure 5. Treatment of intestine-liver MPS with FXR agonist induces synergistic responses from both organ models. Liver MPS and intestine liver MPS were cultured for seven days, in either the PhysioMimix Liver-12 or Dual-organ plates and dosed with FXR agonist OCA - 20 µM in the apical compartment of the intestine MPS and cultured for 48 hours. A) Schematic representation of the transfer of OCA between the two tissue models.
The dual-organ intestine-liver MPS’s capability to maintain the linked tissue models for over one week of culture was also demonstrated, recapitulating first-pass metabolism after oral drug delivery.
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