AccScience Publishing / IJB / Volume 9 / Issue 4 / DOI: 10.18063/ijb.715
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RESEARCH ARTICLE

Biomimetic three-dimensional glioma model printed in vitro for the studies of glioma cells and neurons interactions

Luge Bai1,2 Zhiyan Hao1,2 Sen Wang1,2 Jiajia Zhou1,2 Siqi Yao1,2, Na Pei1,2 Hui Zhu1,2 Kun Zhang3 Rui L. Reis4,5 J. Miguel Oliveira4,5 Jiankang He1,2 Dichen Li1,2 Xinggang Mao6 * Ling Wang1,2*
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1 School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710054, Shaanxi, China
2 NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi’an Jiaotong University, Xi’an 710054, Shaanxi, China
3 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, Shaanxi, China
4 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco -Guimarães, Portugal
5 ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portuga
6 Department of Neurosurgery, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shaanxi, China
© Invalid date by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

The interactions between glioma cells and neurons are important for glioma progression but are rarely mimicked and recapitulated in in vitro three-dimensional (3D) models, which may affect the success rate of relevant drug research and development. In this study, an in vitro bioprinted 3D glioma model consisting of an outer hemispherical shell with neurons and an inner hemisphere with glioma cells is proposed to simulate the natural glioma. This model was produced by extrusion-based 3D bioprinting technology. The cells survival rate, morphology, and intercellular Ca2+ concentration studies were carried out up to 5 days of culturing. It was found that neurons could promote the proliferation of glioma cells around them, associate the morphological changes of glioma cells to be neuron-like, and increase the expression of intracellular Ca2+ of glioma cells. Conversely, the presence of glioma cells could maintain the neuronal survival rate and promote the neurite outgrowth. The results indicated that glioma cells and neurons facilitated each other implying a symbiotic pattern established between two types of cells during the early stage of glioma development, which were seldom found in the present artificial glioma models. The proposed bioprinted glioma model can mimic the natural microenvironment of glioma tissue, provide an in-depth understanding of cell–cell interactions, and enable pathological and pharmacological studies of glioma.

Keywords
In vitro 3D model
Glioma model
3D bioprinting
Glioma cells
Neurons
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing