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

International Journal of Molecular Sciences
Elena NaumovskaDorota Kurek

Abstract

Intestinal organoids have emerged as the new paradigm for modelling the healthy and diseased intestine with patient-relevant properties. In this study, we show directed differentiation of induced pluripotent stem cells towards intestinal-like phenotype within a microfluidic device. iPSCs are cultured against a gel in microfluidic chips of the OrganoPlate, in which they undergo stepwise differentiation. Cells form a tubular structure, lose their stem cell markers and start expressing mature intestinal markers, including markers for Paneth cells, enterocytes and neuroendocrine cells. Tubes develop barrier properties as confirmed by transepithelial electrical resistance (TEER). Lastly, we show that tubules respond to pro-inflammatory cytokine triggers. The whole procedure for differentiation lasts 14 days, making it an efficient process to make patient-specific organoid tubules. We anticipate the usage of the platform for disease modelling and drug candidate screening.

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Citations

Feb 4, 2021·Reproductive Sciences·Yong Song, Asgerally T Fazleabas
Dec 29, 2020·Frontiers in Bioengineering and Biotechnology·Clare L ThompsonStephen D Thorpe
Mar 7, 2021·Nature Protocols·Linda GijzenHans Clevers
Dec 24, 2020·Small·Ellen FritscheKatharina Koch
May 15, 2021·Integrative Biology : Quantitative Biosciences From Nano to Macro·Johanna S DuttonNancy L Allbritton
Jun 3, 2021·International Journal of Molecular Sciences·Sindhu NaikKai S Erdmann
Jun 4, 2021·Cell Stem Cell·Jane NguyenSharon Gerecht
Jun 11, 2021·Cell Host & Microbe·Jens PuschhofHans Clevers
Aug 15, 2021·Advanced Drug Delivery Reviews·Connor O'FarrellHannah Batchelor
Aug 31, 2021·RSC Chemical Biology·Jannik Bruun LarsenThomas Lars Andresen

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Methods Mentioned

BETA
chip
chips
enzyme-linked immunosorbent assay
Assay
ELISA
PCR

Software Mentioned

ImageXpress
GraphPad Prism
GraphPad
Fiji
OrganoTEER
OrganoPlate

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