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


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.

SUBMITTER: Naumovska E 

PROVIDER: S-EPMC7404294 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Naumovska Elena E   Aalderink Germaine G   Wong Valencia Christian C   Kosim Kinga K   Nicolas Arnaud A   Brown Stephen S   Vulto Paul P   Erdmann Kai S KS   Kurek Dorota D  

International journal of molecular sciences 20200714 14


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 intes  ...[more]

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