Gastrointestinal microphysiological systems

Blutt, Sarah E.; Broughman, James R.; Zou, Winnie Y.; Zeng, Xi; Karandikar, Umesh C.; In, Julie; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Estes, Mary K.

doi:10.1177/1535370217710638

Cited by 31 publications

(33 citation statements)

References 76 publications

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“…Peer‐reviewed literature is emerging with examples of disease models using human microphysiological systems (or organs‐on‐chips) . When combined with patient‐derived or genetically engineered iPSCs to induce disease‐causing mutations, the pathophysiology of rare and ultrarare disease subsets can be elucidated.…”

Section: Use Of Microphysiological Systems (Organ‐on‐a‐chip) For Mechmentioning

confidence: 99%

“…The most common application reported for a microphysiological system is to either predict or characterize the mechanism of on‐target and off‐target drug toxicity in humans . An example of such application is the characterization of hepatotoxicity of several hepatotoxic drugs using human, 3‐D, microfluidic, four‐cell, sequentially layered, self‐assembly liver model .…”

Section: Use Of Microphysiological Systems (Organ‐on‐a‐chip) For Mechmentioning

confidence: 99%

“…31 Peer-reviewed literature is emerging with examples of disease models using human microphysiological systems (or organs-on-chips). [32][33][34] When combined with patient-derived or genetically engineered iPSCs to induce disease-causing mutations, the pathophysiology of rare and ultrarare disease subsets can be elucidated. An example of this is the Figure 2 Potential role of microphysiological systems to inform quantitative clinical pharmacology models.…”

Section: Use Of Microphysiological Systems (Organ-on-a-chip) For Mechmentioning

confidence: 99%

“…The most common application reported for a microphysiological system is to either predict or characterize the mechanism of on-target and off-target drug toxicity in humans. 34,[39][40][41][42] An example of such application is the characterization of hepatotoxicity of several hepatotoxic drugs using human, 3-D, microfluidic, four-cell, sequentially layered, self-assembly liver model. 32 The system reproduced the acute toxicity (1-2 days) seen with a high concentration of troglitazone as well as the gradual and delayed (28 days) toxicity produced by a lower concentration of troglitazone.…”

Section: Toxicitymentioning

confidence: 99%

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Emerging Role of Organ‐on‐a‐Chip Technologies in Quantitative Clinical Pharmacology Evaluation

Isoherranen

Madabushi

Huang

2019

Clinical Translational Sci

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The recently enacted Prescription Drug User Fee Act ( PDUFA ) VI includes in its performance goals “enhancing regulatory science and expediting drug development.” The key elements in “enhancing regulatory decision tools to support drug development and review” include “advancing model‐informed drug development ( MIDD ).” This paper describes (i) the US Food and Drug Administration ( FDA ) Office of Clinical Pharmacology's continuing efforts in developing quantitative clinical pharmacology models (disease, drug, and clinical trial models) to advance MIDD , (ii) how emerging novel tools, such as organ‐on‐a‐chip technologies or microphysiological systems, can provide new insights into physiology and disease mechanisms, biomarker identification and evaluation, and elucidation of mechanisms of adverse drug reactions, and (iii) how the single organ or linked organ microphysiological systems can provide critical system parameters for improved physiologically‐based pharmacokinetic and pharmacodynamic evaluations. Continuous public‐private partnerships are critical to advance this field and in the application of these new technologies in drug development and regulatory review.

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Section: Use Of Microphysiological Systems (Organ‐on‐a‐chip) For Mechmentioning

confidence: 99%

Section: Use Of Microphysiological Systems (Organ‐on‐a‐chip) For Mechmentioning

confidence: 99%

Section: Use Of Microphysiological Systems (Organ-on-a-chip) For Mechmentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 99%

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Emerging Role of Organ‐on‐a‐Chip Technologies in Quantitative Clinical Pharmacology Evaluation

Isoherranen

Madabushi

Huang

2019

Clinical Translational Sci

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“…120 Leukocyte migration and other immune interactions in these organs have been studied using in vitro MPS approaches, 24,25,67 as reviewed elsewhere 120 and in this issue for skin 20 and gut. 17 Multichamber MPS devices have been developed 121 specifically to study the activation of immune cells by the transfer of nutrients across the gastrointestinal epithelium. 122 The ability to study intestinal flora in MPS has already been demonstrated.…”

Section: Mps Immunologymentioning

confidence: 99%

Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology

Watson

Hunziker

Wikswo

2017

Exp Biol Med (Maywood)

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Impact statementMicrophysiological systems (MPS), which include engineered organoids and both individual and coupled organs-on-chips and tissue chips, are a rapidly growing topic of research that addresses the known limitations of conventional cellular monoculture on flat plastic -a wellperfected set of techniques that produces reliable, statistically significant results that may not adequately represent human biology and disease. As reviewed in this article and the others in this thematic issue, MPS research has made notable progress in the past three years in both cell sourcing and characterization. As the field matures, currently identified challenges are being addressed, and new ones are being recognized. Building upon investments by the Defense Advanced Research Projects Agency, National Institutes of Health, Food and Drug Administration, Defense Threat Reduction Agency, and Environmental Protection Agency of more than $200 million since 2012 and sizable corporate spending, academic and commercial players in the MPS community are demonstrating their ability to meet the translational challenges required to apply MPS technologies to accelerate drug development and advance toxicology. AbstractMicrophysiological systems (MPS), which include engineered organoids (EOs), single organ/tissue chips (TCs), and multiple organs interconnected to create miniature in vitro models of human physiological systems, are rapidly becoming effective tools for drug development and the mechanistic understanding of tissue physiology and pathophysiology. The second MPS thematic issue of Experimental Biology and Medicine comprises 15 articles by scientists and engineers from the National Institutes of Health, the IQ Consortium, the Food and Drug Administration, and Environmental Protection Agency, an MPS company, and academia. Topics include the progress, challenges, and future of organs-on-chips, dissemination of TCs into Pharma, children's health protection, liver zonation, liver chips and their coupling to interconnected systems, gastrointestinal MPS, maturation of immature cardiomyocytes in a heart-on-a-chip, coculture of multiple cell types in a human skin construct, use of synthetic hydrogels to create EOs that form neural tissue models, the blood-brain barrier-on-a-chip, MPS models of coupled female reproductive organs, coupling MPS devices to create a body-on-a-chip, and the use of a microformulator to recapitulate endocrine circadian rhythms. While MPS hardware has been relatively stable since the last MPS thematic issue, there have been significant advances in cell sourcing, with increased reliance on human-induced pluripotent stem cells, and in characterization of the genetic and functional cell state in MPS bioreactors. There is growing appreciation of the need to minimize perfusate-to-cell-volume ratios and respect physiological scaling of coupled TCs. Questions asked by drug developers are followed by an analysis of the potential value, costs, and needs of Pharma. Of highest value and lowest switching costs may be the d...

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Pharmacokinetics‐On‐a‐Chip: In Vitro Microphysiological Models for Emulating of Drugs ADME

et al. 2021

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pharmacodynamics (PD), and toxicity studies, of the past century and continue to provide a wealth of knowledge and understanding of various diseases mechanism and therapy. [1][2][3] However, the use of these models in research and industrial applications has been a subject of heated debate, particularly, due to ethical matters and the increasing pressure by the animalright activists. [4] In addition, the phylogenetic difference between laboratory animals and humans may lead to drug failure during human clinical studies. [5] Furthermore, the inherent complexity of the animal's body tissue makes it difficult to interpret the physiological events that characterize the interaction of a particular organ or cells with exogenic factors. [6] In line with regulatory developments precluding the use of animal testing, human in vitro methodologies is required to replace the animal-based testes while permitting equivalent or superior prediction. [7,8] Despite many efforts, no sufficiently acceptable in vitro approaches have been developed to date, and the major gap to predict drug response in human still existed. Utilizing animal models can lead to significant insights into the complex pathophysiology of the disease. [9] However, the pathophysiology may differ between humans and animals. [10,11] Comparing to animal model-based studies, these interactions are less well understood in humans. This is a necessity considering the differences between animal and human immune responses and outcomes in preclinical models versus clinical trials. [10,11] There is consequently a real need for in vitro models of the human organs that closely mimic the physiological processes of disease development with an acceptable level of flexibility, accuracy, and reproducibility for efficient screening of potential drug candidates. Such models would increase the predictability of human response to drugs and reduce experimentation expenses and speed up the screening processes. Failing to produce safe and efficient preclinical leads and drug candidates is associated with overall low R&D efficiency and high cost. The cost of developing a new drug that gains marketing approval is estimated to be $2.6 billion (as of 2013) which includes the in vitro and in vivo animal models during the preclinical and clinical trials stages which may last several Despite many ongoing efforts across the full spectrum of pharmaceutical and biotech industries, drug development is still a costly undertaking that involves a high risk of failure during clinical trials. Animal models played vital roles in understanding the mechanism of human diseases. However, the use of these models has been a subject of heated debate, particularly due to ethical matters and the inevitable pathophysiological differences between animals and humans. Current in vitro models lack the sufficient functionality and predictivity of human pharmacokinetics and toxicity, therefore, are not capable to fully replace animal models. The recent development of microphysiological systems has shown great potentia...

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Gastrointestinal microphysiological systems

Cited by 31 publications

References 76 publications

Emerging Role of Organ‐on‐a‐Chip Technologies in Quantitative Clinical Pharmacology Evaluation

Emerging Role of Organ‐on‐a‐Chip Technologies in Quantitative Clinical Pharmacology Evaluation

Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology

Pharmacokinetics‐On‐a‐Chip: In Vitro Microphysiological Models for Emulating of Drugs ADME

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