Organ-on-chip approaches for intestinal 3D in vitro modelling

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

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Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

Scientific Reports ◽

10.1038/s41598-021-82853-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kornphimol Kulthong ◽

Guido J. E. J. Hooiveld ◽

Loes Duivenvoorde ◽

Ignacio Miro Estruch ◽

Victor Marin ◽

...

Keyword(s):

Gene Expression ◽

Culture Conditions ◽

Gene Set Enrichment Analysis ◽

Shear Stresses ◽

Static Culture ◽

Dynamic Culture ◽

Intestinal Segments ◽

On Chip

AbstractGut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.

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New Endeavors of (Micro)Tissue Engineering: Cells Tissues Organs on-Chip and Communication Thereof

Cells Tissues Organs ◽

10.1159/000516356 ◽

2021 ◽

pp. 1-15

Author(s):

Haysam M.M.A.M. Ahmed ◽

Liliana S. Moreira Teixeira

Keyword(s):

Tissue Engineering ◽

Food Additives ◽

Market Potential ◽

Model Systems ◽

Human Model ◽

Human Stem Cells ◽

Animal Testing ◽

Preclinical Research ◽

On Chip

The development of new therapies is tremendously hampered by the insufficient availability of human model systems suitable for preclinical research on disease target identification, drug efficacy, and toxicity. Thus, drug failures in clinical trials are too common and too costly. Animal models or standard 2D in vitro tissue cultures, regardless of whether they are human based, are regularly not representative of specific human responses. Approaching near human tissues and organs test systems is the key goal of organs-on-chips (OoC) technology. This technology is currently showing its potential to reduce both drug development costs and time-to-market, while critically lessening animal testing. OoC are based on human (stem) cells, potentially derived from healthy or disease-affected patients, thereby amenable to personalized therapy development. It is noteworthy that the OoC market potential goes beyond pharma, with the possibility to test cosmetics, food additives, or environmental contaminants. This (micro)tissue engineering-based technology is highly multidisciplinary, combining fields such as (developmental) biology, (bio)materials, microfluidics, sensors, and imaging. The enormous potential of OoC is currently facing an exciting new challenge: emulating cross-communication between tissues and organs, to simulate more complex systemic responses, such as in cancer, or restricted to confined environments, as occurs in osteoarthritis. This review describes key examples of multiorgan/tissue-on-chip approaches, or linked organs/tissues-on-chip, focusing on challenges and promising new avenues of this advanced model system. Additionally, major emphasis is given to the translation of established tissue engineering approaches, bottom up and top down, towards the development of more complex, robust, and representative (multi)organ/tissue-on-chip approaches.

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Overview of existing in vitro BBB models: advantages and disadvantages, current state and future prospects

Complex Issues of Cardiovascular Diseases ◽

10.17802/2306-1278-2021-10-3-109-120 ◽

2021 ◽

Vol 10 (3) ◽

pp. 109-120

Author(s):

A. I. Mosiagina ◽

A. V. Morgun ◽

A. B. Salmina

Keyword(s):

Neurovascular Unit ◽

Clinical Trial Data ◽

Advantages And Disadvantages ◽

The Central Nervous System ◽

Complex Relationships ◽

On Chip ◽

Induced Pluripotent ◽

Level Of Understanding

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

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Pumpless Microfluidic System for Bone Marrow Niche-on-a-Chip in vitro Modelling and Multiphoton Imaging in Leukemia

Biophysical Journal ◽

10.1016/j.bpj.2019.11.2574 ◽

2020 ◽

Vol 118 (3) ◽

pp. 463a

Author(s):

Giulia Borile ◽

Giulia Borella ◽

Camille Charoy ◽

Andrea Filippi ◽

Filippo Romanato ◽

...

Keyword(s):

Bone Marrow ◽

Microfluidic System ◽

Bone Marrow Niche ◽

Multiphoton Imaging ◽

In Vitro Modelling

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In vitro modelling of a mechanism of drug-related hypersensitivity

Biochemical Society Transactions ◽

10.1042/bst020043s ◽

1992 ◽

Vol 20 (1) ◽

pp. 43S-43S

Author(s):

W. ROGER RUSH ◽

JANICE H. MULVEY ◽

DOUGLAS J.M. GRAHAM

Keyword(s):

In Vitro Modelling

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Particle Accumulation in Ureteral Stents Is Governed by Fluid Dynamics: In Vitro Study Using a “Stent-on-Chip” Model

Journal of Endourology ◽

10.1089/end.2017.0946 ◽

2018 ◽

Vol 32 (7) ◽

pp. 639-646 ◽

Cited By ~ 11

Author(s):

Ali Mosayyebi ◽

Qi Yann Yue ◽

Bhaskar K. Somani ◽

Xunli Zhang ◽

Costantino Manes ◽

...

Keyword(s):

Fluid Dynamics ◽

In Vitro Study ◽

Vitro Study ◽

Ureteral Stents ◽

Particle Accumulation ◽

On Chip

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CTCF Interacts with and Recruits the Largest Subunit of RNA Polymerase II to CTCF Target Sites Genome-Wide

Molecular and Cellular Biology ◽

10.1128/mcb.01993-06 ◽

2007 ◽

Vol 27 (5) ◽

pp. 1631-1648 ◽

Cited By ~ 104

Author(s):

Igor Chernukhin ◽

Shaharum Shamsuddin ◽

Sung Yun Kang ◽

Rosita Bergström ◽

Yoo-Wook Kwon ◽

...

Keyword(s):

Rna Polymerase ◽

Rna Polymerase Ii ◽

Gene Activation ◽

Ctcf Binding ◽

Pol Ii ◽

Genome Wide ◽

Target Sites ◽

On Chip

ABSTRACT CTCF is a transcription factor with highly versatile functions ranging from gene activation and repression to the regulation of insulator function and imprinting. Although many of these functions rely on CTCF-DNA interactions, it is an emerging realization that CTCF-dependent molecular processes involve CTCF interactions with other proteins. In this study, we report the association of a subpopulation of CTCF with the RNA polymerase II (Pol II) protein complex. We identified the largest subunit of Pol II (LS Pol II) as a protein significantly colocalizing with CTCF in the nucleus and specifically interacting with CTCF in vivo and in vitro. The role of CTCF as a link between DNA and LS Pol II has been reinforced by the observation that the association of LS Pol II with CTCF target sites in vivo depends on intact CTCF binding sequences. “Serial” chromatin immunoprecipitation (ChIP) analysis revealed that both CTCF and LS Pol II were present at the β-globin insulator in proliferating HD3 cells but not in differentiated globin synthesizing HD3 cells. Further, a single wild-type CTCF target site (N-Myc-CTCF), but not the mutant site deficient for CTCF binding, was sufficient to activate the transcription from the promoterless reporter gene in stably transfected cells. Finally, a ChIP-on-ChIP hybridization assay using microarrays of a library of CTCF target sites revealed that many intergenic CTCF target sequences interacted with both CTCF and LS Pol II. We discuss the possible implications of our observations with respect to plausible mechanisms of transcriptional regulation via a CTCF-mediated direct link of LS Pol II to the DNA.

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