Studying Metabolism with Multi-Organ Chips: New Tools for Disease Modelling, Pharmacokinetics and Pharmacodynamics

Tanvi Shrof; Kehinde Aina; Christian Maass; Madalena Cipriano; Joeri Lambrecht; Frank Tacke; Alexander Mosig; Peter Loskill

doi:10.1201/9781003298038-52

Studying Metabolism with Multi-Organ Chips: New Tools for Disease Modelling, Pharmacokinetics and Pharmacodynamics

Tanvi Shrof, Kehinde Aina, Christian Maass, Madalena Cipriano, Joeri Lambrecht, Frank Tacke, Alexander Mosig, Peter Loskill

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

Abstract

The intestinal epithelial cells have a large surface area for absorption and metabolism, and the ability to regenerate, thus maintaining intestinal function. These include organ-specific PK aspects such as absorption in the gut, partitioning of the drug into adipose tissue, liver metabolism of the drug or excretion of the drug in the kidney. The usage of automated robotic systems to study metabolism in multiple organ models has recently been proposed by Novak et al. Carbohydrate and protein metabolism was captured in a study by Maass et al., who monitored gut, liver and cardiac OoCs over a period of one week in order to gauge nutrient consumption and metabolic profiles. Metabolic diseases represent a spectrum of disorders ranging from obesity, coronary artery disease, cardiovascular diseases, non-alcoholic fatty liver disease [NAFLD] and type 2 diabetes. Mechanistic toxicology is the identification and understanding of the cellular, biochemical and molecular mechanisms by which chemicals or drugs exert toxic effects.

Original language	English
Title of host publication	Advances in Medical Imaging, Detection, and Diagnosis
Publisher	Jenny Stanford Publishing
Pages	1273-1315
Number of pages	43
ISBN (Electronic)	9781000602043
ISBN (Print)	9789814877466
DOIs	https://doi.org/10.1201/9781003298038-52
State	Published - 1 Jan 2023
Externally published	Yes

Keywords

adiponectin (APN)
adsorption
adverse outcome pathway (AOP)
asthma
autocrine
biomarker
cyclic olefin copolymer (COC)
distribution
drug metabolism
excretion and toxicity (ADMET)
fatty acid oxidation
free fatty acids (FFAs)
gluconeogenesis
glycolysis
hepatocytes
homeostasis
human-on-a-chip
hydrocortisone (HC)
in silico models
in situ readout
in vitro to in vivo extrapolation (IVIVE)
in vitro-in vivo translation (IVIVT)
induced pluripotent stem cells (iPSCs)
inflammatory bowel disease
kidney-injury marker (KIM-1)
liver disease
metabolic disease
metabolic regulation
metabolism
microfabrication
microfluidics
microphysiological system (MPS)
multi-analyte biosensor
multi-organ chip (MOC)
non-alcoholic fatty liver disease (NAFLD)
non-alcoholic steatohepatitis (NASH)
organ crosstalk
organ-on-chip (OoC)
paracrine
pharmacodynamics (PD)
pharmacokinetics (PK)
physiologically based PK-PD (PBPK-PD)
polydimethylsiloxane (PDMS)
polymethyl methacrylate (PMMA)
quantitative systems pharmacology (QSP)
reactive oxygen species
signaling pathways
tricarboxylic acid (TCA)
type 2 diabetes mellitus (T2D)
vasculature-like perfusion

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10.1201/9781003298038-52

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title = "Studying Metabolism with Multi-Organ Chips: New Tools for Disease Modelling, Pharmacokinetics and Pharmacodynamics",

abstract = "The intestinal epithelial cells have a large surface area for absorption and metabolism, and the ability to regenerate, thus maintaining intestinal function. These include organ-specific PK aspects such as absorption in the gut, partitioning of the drug into adipose tissue, liver metabolism of the drug or excretion of the drug in the kidney. The usage of automated robotic systems to study metabolism in multiple organ models has recently been proposed by Novak et al. Carbohydrate and protein metabolism was captured in a study by Maass et al., who monitored gut, liver and cardiac OoCs over a period of one week in order to gauge nutrient consumption and metabolic profiles. Metabolic diseases represent a spectrum of disorders ranging from obesity, coronary artery disease, cardiovascular diseases, non-alcoholic fatty liver disease [NAFLD] and type 2 diabetes. Mechanistic toxicology is the identification and understanding of the cellular, biochemical and molecular mechanisms by which chemicals or drugs exert toxic effects.",

keywords = "adiponectin (APN), adsorption, adverse outcome pathway (AOP), asthma, autocrine, biomarker, cyclic olefin copolymer (COC), distribution, drug metabolism, excretion and toxicity (ADMET), fatty acid oxidation, free fatty acids (FFAs), gluconeogenesis, glycolysis, hepatocytes, homeostasis, human-on-a-chip, hydrocortisone (HC), in silico models, in situ readout, in vitro to in vivo extrapolation (IVIVE), in vitro-in vivo translation (IVIVT), induced pluripotent stem cells (iPSCs), inflammatory bowel disease, kidney-injury marker (KIM-1), liver disease, metabolic disease, metabolic regulation, metabolism, microfabrication, microfluidics, microphysiological system (MPS), multi-analyte biosensor, multi-organ chip (MOC), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), organ crosstalk, organ-on-chip (OoC), paracrine, pharmacodynamics (PD), pharmacokinetics (PK), physiologically based PK-PD (PBPK-PD), polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), quantitative systems pharmacology (QSP), reactive oxygen species, signaling pathways, tricarboxylic acid (TCA), type 2 diabetes mellitus (T2D), vasculature-like perfusion",

author = "Tanvi Shrof and Kehinde Aina and Christian Maass and Madalena Cipriano and Joeri Lambrecht and Frank Tacke and Alexander Mosig and Peter Loskill",

note = "Publisher Copyright: {\textcopyright} 2023 Jenny Stanford Publishing Pte. Ltd.",

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AU - Shrof, Tanvi

AU - Aina, Kehinde

AU - Maass, Christian

AU - Cipriano, Madalena

AU - Lambrecht, Joeri

AU - Tacke, Frank

AU - Mosig, Alexander

AU - Loskill, Peter

PY - 2023/1/1

Y1 - 2023/1/1

N2 - The intestinal epithelial cells have a large surface area for absorption and metabolism, and the ability to regenerate, thus maintaining intestinal function. These include organ-specific PK aspects such as absorption in the gut, partitioning of the drug into adipose tissue, liver metabolism of the drug or excretion of the drug in the kidney. The usage of automated robotic systems to study metabolism in multiple organ models has recently been proposed by Novak et al. Carbohydrate and protein metabolism was captured in a study by Maass et al., who monitored gut, liver and cardiac OoCs over a period of one week in order to gauge nutrient consumption and metabolic profiles. Metabolic diseases represent a spectrum of disorders ranging from obesity, coronary artery disease, cardiovascular diseases, non-alcoholic fatty liver disease [NAFLD] and type 2 diabetes. Mechanistic toxicology is the identification and understanding of the cellular, biochemical and molecular mechanisms by which chemicals or drugs exert toxic effects.

AB - The intestinal epithelial cells have a large surface area for absorption and metabolism, and the ability to regenerate, thus maintaining intestinal function. These include organ-specific PK aspects such as absorption in the gut, partitioning of the drug into adipose tissue, liver metabolism of the drug or excretion of the drug in the kidney. The usage of automated robotic systems to study metabolism in multiple organ models has recently been proposed by Novak et al. Carbohydrate and protein metabolism was captured in a study by Maass et al., who monitored gut, liver and cardiac OoCs over a period of one week in order to gauge nutrient consumption and metabolic profiles. Metabolic diseases represent a spectrum of disorders ranging from obesity, coronary artery disease, cardiovascular diseases, non-alcoholic fatty liver disease [NAFLD] and type 2 diabetes. Mechanistic toxicology is the identification and understanding of the cellular, biochemical and molecular mechanisms by which chemicals or drugs exert toxic effects.

KW - adiponectin (APN)

KW - adsorption

KW - adverse outcome pathway (AOP)

KW - asthma

KW - autocrine

KW - biomarker

KW - cyclic olefin copolymer (COC)

KW - distribution

KW - drug metabolism

KW - excretion and toxicity (ADMET)

KW - fatty acid oxidation

KW - free fatty acids (FFAs)

KW - gluconeogenesis

KW - glycolysis

KW - hepatocytes

KW - homeostasis

KW - human-on-a-chip

KW - hydrocortisone (HC)

KW - in silico models

KW - in situ readout

KW - in vitro to in vivo extrapolation (IVIVE)

KW - in vitro-in vivo translation (IVIVT)

KW - induced pluripotent stem cells (iPSCs)

KW - inflammatory bowel disease

KW - kidney-injury marker (KIM-1)

KW - liver disease

KW - metabolic disease

KW - metabolic regulation

KW - metabolism

KW - microfabrication

KW - microfluidics

KW - microphysiological system (MPS)

KW - multi-analyte biosensor

KW - multi-organ chip (MOC)

KW - non-alcoholic fatty liver disease (NAFLD)

KW - non-alcoholic steatohepatitis (NASH)

KW - organ crosstalk

KW - organ-on-chip (OoC)

KW - paracrine

KW - pharmacodynamics (PD)

KW - pharmacokinetics (PK)

KW - physiologically based PK-PD (PBPK-PD)

KW - polydimethylsiloxane (PDMS)

KW - polymethyl methacrylate (PMMA)

KW - quantitative systems pharmacology (QSP)

KW - reactive oxygen species

KW - signaling pathways

KW - tricarboxylic acid (TCA)

KW - type 2 diabetes mellitus (T2D)

KW - vasculature-like perfusion

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U2 - 10.1201/9781003298038-52

DO - 10.1201/9781003298038-52

M3 - Chapter

AN - SCOPUS:85177536683

SN - 9789814877466

SP - 1273

EP - 1315

BT - Advances in Medical Imaging, Detection, and Diagnosis

PB - Jenny Stanford Publishing

ER -

Studying Metabolism with Multi-Organ Chips: New Tools for Disease Modelling, Pharmacokinetics and Pharmacodynamics

Abstract

Keywords

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