Application of microfluidic devices for glioblastoma study: current status and future directions
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Application of microfluidic devices for glioblastoma study: current status and future directions Xue Cai 1 & Robert G. Briggs 1 & Hannah B. Homburg 1 & Isabella M. Young 3 & Ethan J. Davis 3 & Yueh-Hsin Lin 4 & James D. Battiste 2 & Michael E. Sughrue 3,5
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Glioblastoma (GBM) is one of the most malignant primary brain tumors. This neoplasm is the hardest to treat and has a bad prognosis. Because of the characteristics of genetic heterogeneity and frequent recurrence, a successful cure for the disease is unlikely. Increasing evidence has revealed that the GBM stem cell-like cells (GSCs) and microenvironment are key elements in GBM recurrence and treatment failure. To better understand the mechanisms underlying this disease and to develop more effective therapeutic strategies for treatment, suitable approaches, techniques, and model systems closely mimicking real GBM conditions are required. Microfluidic devices, a model system mimicking the in vivo brain microenvironment, provide a very useful tool to analyze GBM cell behavior, their correlation with tumor malignancy, and the efficacy of multiple drug treatment. This paper reviews the applications of microfluidic devices in GBM research and summarizes progress and perspectives in this field. Keywords Glioblastoma . Microfluidic device . Microenvironment . Single cells . Cell migration
1 Introduction There is an urgent need to better understand the cause of cancers, including glioblastoma (GBM). Investigating the cellular and molecular biology of cancer cells in tumor microenvironments is essential to developing effective treatments and understanding the pathogenesis and progression of cancers. Ample evidence suggests that the phenotypes and genetic/functional heterogeneity of cancer cells are heavily influenced by tumor microenvironments which play a vital role in tumor metastasis and recurrence (Bedard et al. 2013; Burrell et al. 2013). Because of the
* Michael E. Sughrue [email protected] 1
Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2
Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
3
Cingulum Health, Sydney, Australia
4
Centre for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital, Sydney, Australia
5
Centre for Minimally Invasive Neurosurgery, Prince of Wales Private Hospital, Suite 19, Level 7, Barker Street, Randwick, New South Wales 2031, Australia
limitations of microenvironment research in vivo, a model system mimicking tumor microenvironments is essential. Glioblastoma is a World Health Organization (WHO) defined grade IV astrocytoma and is the most malignant and deadly primary brain tumor. Patient survival rate is very low with median survival lasting less than 18 months after treatment (Wang et al. 2015; Stupp et al. 2009). Being the most difficultly treated primary brain cancer, GBM exhibits highly heterogenic phenotypes, high recurrence
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