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Organ-on-a-Chip, Ex vivo model

TOWARDS A PERSONALISED IN VITRO TEST SYSTEM
CONTRACT SERVICE, TECHNOLOGIES OPEN FOR PARTNERING

Ex vivo model; InTESTine

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InTESTine is the opportunity to study multiple intestinal segments (duodenum, jejunum, ileum & colon) in parallel, under controlled conditions, in order to study regional differences in absorption. This is important, as the morphology and function of the intestinal tract changes from duodenum to colon with respect to thickness of the mucus layer, height of the villi, pore size of the tight junctions, expression levels of transporters, receptors and/or metabolizing enzymes. Additionally, due to the presence of the mucus layer, intestinal processes can be studied following exposure to digested samples, and in the absence, or presence of microbiota. This clearly demonstrates the additional value of InTESTine compared to monolayer cultures (e.g. Caco-2 cells) in order to study absorption, metabolism and/or food-drug and excipient-drug interactions of orally administered compounds.

Application
Intestinal absorption of nutrients and drugs:
      > Active transport, metabolism, food-drug effects, excipient-drug effects
Mucus interactions; Adhesion / Secretion
Study regional differences Whole GI tract of pigs available
Effect of compounds on excretion of gut hormones
       > Satiety hormones (GLP-1, PYY), Serotonin, VIP
Host-microbe interactions exposure to pathogens
    Read-out: Local Immunoresponse (Cytokine, Prostaglandins, etc)
    Transcriptomics, Proteomics, Bacterial translation (Pre,Pro-biotics,etc)

  Download:
  InTESTine (Brochure)
  Human ex vivo model to study Intestinal Processes and Microbiome induced Metabolism. Poster ISSX 2018

Intestine-on-a-Chip   (OPEN FOR PARTNERING)

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We aim to develop a physiological in vitro human intestinal model that can be used to study (drug) absorption and impact of drugs, nutrition and microbial environment on gut health. The ultimate goal is to develop a population-on-a-chip model to aid in the development of precision medicines by targeting patient variability using intestinal tissue and microbiota from various individuals reflecting populational variation.

Summary:
・We have developed a novel microfluidic platform with an enhanced throughput to be able to study (drug) absorption, and impact of drugs, nutrition and microbial environment on gut health.
・InTESTine on a Chip can be applied to human intestinal tissue biopsies with remained tissue viability and functionality for 26 hours.
・We are currently using the InTESTine Chip to study in combination with microbial components
to study the influence of host-microbe interactions on drug absorption and immune response

Download:  Flow influences functioning of fresh human intestinal tissue in the inTESTine Chip. Poster at ISSX-2019

Liver-on-a-Chip   (OPEN FOR PARTNERING)

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NAFLD, characterized by hepatocyte steatosis, is the most common form of chronic liver disease and may progress towards development of NASH, cirrhosis and hepatocellular carcinoma. Currently no effective therapeutic treatment is available to halt or reverse progression of NAFLD, partly due to the absence of translational cell models. We present data on induction of steatosis, modulation of steatosis by prototype compounds and profibrotic cell activation in a 3D liver spheroid model using primary human cells.

Summary:
・A diet-induced disease-mimicking 3D in vitro model, closely resembling the pathophysiology of liver steatosis and early fibrosis was developed;
・Liver spheroids composed of primary hepatocytes, stellate and Kupffer cells exhibit expected cell function for at least 21 days;
・The steatosis and steatohepatitis induced by fatty acids and fructose can be modulated by model drugs;

Download: Development of a diet-induced diseasemimicking in vitro model of non-alcoholic steatohepatitis / fibrosis. Poster at EURO OcC 2019:

Ex vivo whole liver normothermic machine perfusion model (OPEN FOR PARTNERING)

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Prediction of First Pass Liver Effects, Biliary Excretion and DDI
   Porcine Liver model (for contract research)
      > Hepatic Clearance
      > Hepatic Metabolism
      > Biliary Excreation
      > Plasma Exposure upon DDI
      > Dosing to portal vein and/or hepatic artery

   Human Liver model (for collaboration research)
      > Hepatic Clearance
      > Hepatic Metabolism
      > Biliary Excreation
      > Plasma Exposure upon DDI
      > Dosing to portal vein and/or hepatic artery
      > NASH: Biomarker detection / Target Binding

  Download:
  Ex vivo whole liver perfusion model for prediction of drug drug interactions and biliary excretion of Rosuvastatin (Poster)
  Pharmacokinetics Application of Normothermic Perfused Ex Vivo Porcine Livers. Poster ISSX-2019


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