High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarray

Abstract Most of the biological processes, including cell signaling, cancer invasion, embryogenesis, or neural development, are dependent on and guided by the complex architecture and composition of cellular microenvironments. Mimicking such microenvironments in cell coculture models is crucial for...

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Main Authors: Haijun Cui, Tina Tronser, Xianxian Wang, Janine Wesslowski, Gary Davidson, Anna A. Popova, Pavel A. Levkin
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Droplet
Online Access:https://doi.org/10.1002/dro2.39
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author Haijun Cui
Tina Tronser
Xianxian Wang
Janine Wesslowski
Gary Davidson
Anna A. Popova
Pavel A. Levkin
author_facet Haijun Cui
Tina Tronser
Xianxian Wang
Janine Wesslowski
Gary Davidson
Anna A. Popova
Pavel A. Levkin
author_sort Haijun Cui
collection DOAJ
description Abstract Most of the biological processes, including cell signaling, cancer invasion, embryogenesis, or neural development, are dependent on and guided by the complex architecture and composition of cellular microenvironments. Mimicking such microenvironments in cell coculture models is crucial for fundamental and applied biology investigations. The ability to combine different cell types grown as both two‐dimensional (2D) monolayers and three‐dimensional (3D) spheroids in specific defined location inside a microculture environments is a key towards in vitro tissue modeling and towards mimicking complex in vivo cellular processes. In this study, we introduce and investigate a method to create in vitro models of 2D cell monolayers cocultured with 3D spheroids in defined preorganization. We demonstrate the possibility of creating such complex cellular microenvironments in a high‐throughput and automated manner by creating arrays of such droplets containing prearranged 2D and 3D cellular microcolonies. Furthermore, we demonstrate an application of this approach to study paracrine propagation of Wnt signaling between 2D and 3D cellular colonies. This method provides a general approach for the miniaturized, high‐throughput, and automated formation of complex coculture cellular microarchitectures that will be useful for mimicking various in vivo complex cellular structures and for studying complex biological processes in vitro.
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spelling doaj.art-744a5e59683e4135999b6aead797e6082023-11-22T16:25:35ZengWileyDroplet2731-43752023-01-0121n/an/a10.1002/dro2.39High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarrayHaijun Cui0Tina Tronser1Xianxian Wang2Janine Wesslowski3Gary Davidson4Anna A. Popova5Pavel A. Levkin6Institute of Biological and Chemical Systems‐Functional Molecular Systems (IBCS‐FMS) Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems‐Functional Molecular Systems (IBCS‐FMS) Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems‐Functional Molecular Systems (IBCS‐FMS) Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems‐Functional Molecular Systems (IBCS‐FMS) Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems‐Functional Molecular Systems (IBCS‐FMS) Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems‐Functional Molecular Systems (IBCS‐FMS) Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen GermanyInstitute of Biological and Chemical Systems‐Functional Molecular Systems (IBCS‐FMS) Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen GermanyAbstract Most of the biological processes, including cell signaling, cancer invasion, embryogenesis, or neural development, are dependent on and guided by the complex architecture and composition of cellular microenvironments. Mimicking such microenvironments in cell coculture models is crucial for fundamental and applied biology investigations. The ability to combine different cell types grown as both two‐dimensional (2D) monolayers and three‐dimensional (3D) spheroids in specific defined location inside a microculture environments is a key towards in vitro tissue modeling and towards mimicking complex in vivo cellular processes. In this study, we introduce and investigate a method to create in vitro models of 2D cell monolayers cocultured with 3D spheroids in defined preorganization. We demonstrate the possibility of creating such complex cellular microenvironments in a high‐throughput and automated manner by creating arrays of such droplets containing prearranged 2D and 3D cellular microcolonies. Furthermore, we demonstrate an application of this approach to study paracrine propagation of Wnt signaling between 2D and 3D cellular colonies. This method provides a general approach for the miniaturized, high‐throughput, and automated formation of complex coculture cellular microarchitectures that will be useful for mimicking various in vivo complex cellular structures and for studying complex biological processes in vitro.https://doi.org/10.1002/dro2.39
spellingShingle Haijun Cui
Tina Tronser
Xianxian Wang
Janine Wesslowski
Gary Davidson
Anna A. Popova
Pavel A. Levkin
High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarray
Droplet
title High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarray
title_full High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarray
title_fullStr High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarray
title_full_unstemmed High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarray
title_short High‐throughput formation of miniaturized cocultures of 2D cell monolayers and 3D cell spheroids using droplet microarray
title_sort high throughput formation of miniaturized cocultures of 2d cell monolayers and 3d cell spheroids using droplet microarray
url https://doi.org/10.1002/dro2.39
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