Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips

Abstract In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with ded...

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Autores principales:	H. H. T. Middelkamp, A. H. A. Verboven, A. G. De Sá Vivas, C. Schoenmaker, T. M. Klein Gunnewiek, R. Passier, C. A. Albers, P. A. C. ‘t Hoen, N. Nadif Kasri, A. D. van der Meer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/801201348ddd426a9c4934d59048c886
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spelling	oai:doaj.org-article:801201348ddd426a9c4934d59048c8862021-12-02T14:16:17ZCell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips10.1038/s41598-021-81933-x2045-2322https://doaj.org/article/801201348ddd426a9c4934d59048c8862021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81933-xhttps://doaj.org/toc/2045-2322Abstract In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.H. H. T. MiddelkampA. H. A. VerbovenA. G. De Sá VivasC. SchoenmakerT. M. Klein GunnewiekR. PassierC. A. AlbersP. A. C. ‘t HoenN. Nadif KasriA. D. van der MeerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q H. H. T. Middelkamp A. H. A. Verboven A. G. De Sá Vivas C. Schoenmaker T. M. Klein Gunnewiek R. Passier C. A. Albers P. A. C. ‘t Hoen N. Nadif Kasri A. D. van der Meer Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips
description	Abstract In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.
format	article
author	H. H. T. Middelkamp A. H. A. Verboven A. G. De Sá Vivas C. Schoenmaker T. M. Klein Gunnewiek R. Passier C. A. Albers P. A. C. ‘t Hoen N. Nadif Kasri A. D. van der Meer
author_facet	H. H. T. Middelkamp A. H. A. Verboven A. G. De Sá Vivas C. Schoenmaker T. M. Klein Gunnewiek R. Passier C. A. Albers P. A. C. ‘t Hoen N. Nadif Kasri A. D. van der Meer
author_sort	H. H. T. Middelkamp
title	Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips
title_short	Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips
title_full	Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips
title_fullStr	Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips
title_full_unstemmed	Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips
title_sort	cell type-specific changes in transcriptomic profiles of endothelial cells, ipsc-derived neurons and astrocytes cultured on microfluidic chips
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/801201348ddd426a9c4934d59048c886
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Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips

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