Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells
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 culture...
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doaj-1ea9d809a892451f9e03eb03a91af37f2020-11-25T02:17:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-01214964496410.3390/ijms21144964Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem CellsElena Naumovska0Germaine Aalderink1Christian Wong Valencia2Kinga Kosim3Arnaud Nicolas4Stephen Brown5Paul Vulto6Kai S. Erdmann7Dorota Kurek8Mimetas BV, Model Development, J.H. Oortweg 16, 2333 CH Leiden, The NetherlandsMimetas BV, Model Development, J.H. Oortweg 16, 2333 CH Leiden, The NetherlandsDepartment of Biomedical Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UKMimetas BV, Model Development, J.H. Oortweg 16, 2333 CH Leiden, The NetherlandsMimetas BV, Model Development, J.H. Oortweg 16, 2333 CH Leiden, The NetherlandsDepartment of Biomedical Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UKMimetas BV, Model Development, J.H. Oortweg 16, 2333 CH Leiden, The NetherlandsDepartment of Biomedical Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UKMimetas BV, Model Development, J.H. Oortweg 16, 2333 CH Leiden, The NetherlandsIntestinal 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.https://www.mdpi.com/1422-0067/21/14/4964iPSCintestinal organoidsdirected differentiationgut-on-a-chiporgan-on-a-chipmicrofluidics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elena Naumovska Germaine Aalderink Christian Wong Valencia Kinga Kosim Arnaud Nicolas Stephen Brown Paul Vulto Kai S. Erdmann Dorota Kurek |
spellingShingle |
Elena Naumovska Germaine Aalderink Christian Wong Valencia Kinga Kosim Arnaud Nicolas Stephen Brown Paul Vulto Kai S. Erdmann Dorota Kurek Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells International Journal of Molecular Sciences iPSC intestinal organoids directed differentiation gut-on-a-chip organ-on-a-chip microfluidics |
author_facet |
Elena Naumovska Germaine Aalderink Christian Wong Valencia Kinga Kosim Arnaud Nicolas Stephen Brown Paul Vulto Kai S. Erdmann Dorota Kurek |
author_sort |
Elena Naumovska |
title |
Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells |
title_short |
Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells |
title_full |
Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells |
title_fullStr |
Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells |
title_full_unstemmed |
Direct On-Chip Differentiation of Intestinal Tubules from Induced Pluripotent Stem Cells |
title_sort |
direct on-chip differentiation of intestinal tubules from induced pluripotent stem cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-07-01 |
description |
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. |
topic |
iPSC intestinal organoids directed differentiation gut-on-a-chip organ-on-a-chip microfluidics |
url |
https://www.mdpi.com/1422-0067/21/14/4964 |
work_keys_str_mv |
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