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World J Stem Cells. Aug 26, 2021; 13(8): 1112-1126
Published online Aug 26, 2021. doi: 10.4252/wjsc.v13.i8.1112
Central nervous system tumors and three-dimensional cell biology: Current and future perspectives in modeling
Zaki Abou-Mrad, Jolie Bou Gharios, Maya M Moubarak, Ahmad Chalhoub, Charbel Moussalem, Hisham F Bahmad, Wassim Abou-Kheir
Zaki Abou-Mrad, Jolie Bou Gharios, Maya M Moubarak, Ahmad Chalhoub, Hisham F Bahmad, Wassim Abou-Kheir, Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107-2020, Lebanon
Charbel Moussalem, Division of Neurosurgery, Department of Surgery, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
Hisham F Bahmad, Arkadi M. Rywlin M.D. Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, United States
Author contributions: Abou-Mrad Z contributed investigation, methodology, visualization, and validation, wrote the original draft, and reviewed and edited the manuscript; Gharios JB, Moubarak MM, Chalhoub A, and Moussalem C contributed investigation, methodology, and validation, wrote the original draft, and reviewed and edited the manuscript; Bahmad HF contributed investigation, project administration, visualization, and validation reviewed and edited the manuscript; Abou-Kheir W contributed conceptualization, project administration, supervision, validation, and visualization, reviewed and edited the manuscript, and gave final approval.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wassim Abou-Kheir, MSc, PhD, Associate Professor, Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Bliss Street, DTS Bldg, Beirut 1107-2020, Lebanon. wa12@aub.edu.lb
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: April 19, 2021
Revised: May 2, 2021
Accepted: July 7, 2021
Article in press: July 7, 2021
Published online: August 26, 2021
Abstract

Central nervous system (CNS) tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis. Glioblastoma, the most common primary tumor in adults, is associated with poor survival and remains one of the least treatable neoplasms. These tumors are highly heterogenous and complex in their nature. Due to this complexity, traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’ behavior in vivo. Two-dimensional models lack the spatial arrangement, the heterogeneity in cell types, and the microenvironment that play a large role in tumor cell behavior and response to treatment. Recently, scientists have turned towards three-dimensional culturing methods, namely spheroids and organoids, as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts. Moreover, tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing. In this review, we will discuss the current available literature on in vitro three-dimensional culturing models in CNS tumors, in addition to presenting their advantages and current limitations. We will also elaborate on the future implications of these models and their benefit in the clinical setting.

Keywords: Central nervous system tumors, Glioblastoma, Three-dimensional modelling, Spheroids, Organoids

Core Tip: Central nervous system tumors present multiple challenges in treatment and patient prognosis. Glioblastoma, the most common adult brain tumor, remains one of the most lethal malignant brain tumors even at the current standard of care. Traditional in vitro culturing is limited in recapitulating the features of the in vivo tumors. We herein discuss recent advancements in three-dimensional culturing for tumor modeling, their advantages, and limitations, in addition to future perspectives.