Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells

Naumovska, Elena; Aalderink, Germaine; Valencia, Christian Wong; Kosim, Kinga; Nicolas, Arnaud; Brown, Stephen; Vulto, Paul; Erdmann, Kai S.; Kurek, Dorota

doi:10.3390/ijms21144964

Cited by 57 publications

(54 citation statements)

References 65 publications

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“…Through the addition of a cytokine cocktail of IL-1β, tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ), they were able to replicate the loss of barrier function observed in irritable bowel disease (Beaurivage et al, 2019). Similar results were achieved using iPSCs which can be induced to undergo differentiation within the Organoplate R to express mature intestinal markers, including markers for Paneth cells, enterocytes and neuroendocrine cells (Naumovska et al, 2020).…”

Section: Intestine Modelsmentioning

confidence: 84%

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

Thompson

Knight

et al. 2020

Front. Bioeng. Biotechnol.

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Organ-on-chip (OOC) systems recapitulate key biological processes and responses in vitro exhibited by cells, tissues, and organs in vivo. Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of in vivo behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating in vivo physiology in health and disease.

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Section: Intestine Modelsmentioning

confidence: 84%

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

Thompson

Knight

et al. 2020

Front. Bioeng. Biotechnol.

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“…Having demonstrated that our OCRL KO HK-2 cell lines display hallmarks of the phenotype described previously for cells isolated from Lowe syndrome patients, or in animal Lowe syndrome models, we incorporated our cell lines into a three-lane OrganoPlate ® . OrganoPlate is a recently developed microfluidic platform that allows for the growth of 3D proximal tubules in a microfluidic setup [35][36][37]. Cells were seeded into the top channel, then the middle channel was filled with ECM (collagen I) and the bottom channel was filled with medium.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, our human in vitro model could also prove useful in small molecule screens or drug validation, in particular if further improved by replacing HK-2 cells by proximal tubule cells isolated from patients or by generating proximal tubule cells from induced pluripotent stem cells [41,42]. We demonstrated, recently, the on-chip differentiation of pluripotent stem cells into intestinal tubules [37].…”

Section: Discussionmentioning

confidence: 99%

A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy

Naik

Wood

Ongenaert

et al. 2021

IJMS

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Lowe syndrome and Dent II disease are X-linked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositol-5-phosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in vitro models for Lowe syndrome/Dent II disease to study the underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here, we describe a proximal tubule organ on chip model combining a 3D tubule architecture with fluid flow shear stress that phenocopies hallmarks of Lowe syndrome/Dent II disease. We demonstrate the high suitability of our in vitro model for drug target validation. Furthermore, using this model, we demonstrate that proximal tubule cells lacking OCRL expression upregulate markers typical for epithelial–mesenchymal transition (EMT), including the transcription factor SNAI2/Slug, and show increased collagen expression and deposition, which potentially contributes to interstitial fibrosis and disease progression as observed in Lowe syndrome and Dent II disease.

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“…A commercially available microfluidic chip, Organoplate, [298] has been employed to develop 3D models of BBB-on-chip, [295] glioma-on-chip, [299] gut-on-chip, [300] and vessel-on-chip. [301] Organoplate is a three-lane microfluidic chip fabricated in www.advancedsciencenews.com www.advancedscience.com microtiter plate format comprising 96 tissue chips that can be used for high-throughput drug screening studies.…”

Section: D Microfluidic Modelsmentioning

confidence: 99%

Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges

et al. 2021

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Neurological disorders such as Alzheimer's disease, stroke, and brain cancers are difficult to treat with current drugs as their delivery efficacy to the brain is severely hampered by the presence of the blood-brain barrier (BBB). Drug delivery systems have been extensively explored in recent decades aiming to circumvent this barrier. In particular, polymeric nanoparticles have shown enormous potentials owing to their unique properties, such as high tunability, ease of synthesis, and control over drug release profile. However, careful analysis of their performance in effective drug transport across the BBB should be performed using clinically relevant testing models. In this review, polymeric nanoparticle systems for drug delivery to the central nervous system are discussed with an emphasis on the effects of particle size, shape, and surface modifications on BBB penetration. Moreover, the authors critically analyze the current in vitro and in vivo models used to evaluate BBB penetration efficacy, including the latest developments in the BBB-on-a-chip models. Finally, the challenges and future perspectives for the development of polymeric nanoparticles to combat neurological disorders are discussed.

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Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells

Cited by 57 publications

References 65 publications

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy

Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges

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