A three-dimensional collagen scaffold cell culture system for screening anti-glioma therapeutics

Abstract

// Donglai Lv 1, 2 , Shi-cang Yu 1, 2 , Yi-fang Ping 1, 2 , Haibo Wu 1, 2 , Xilong Zhao 1, 2 , Huarong Zhang 1, 2 , Youhong Cui 1, 2 , Bing Chen 3, 4 , Xia Zhang 1, 2 , Jianwu Dai 3, 4 , Xiu-wu Bian 1, 2, * , Xiao-hong Yao 1, 2, * 1 Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China 2 Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China 3 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, School of Military Preventive Medicine, Third Military Medical University, Chongqing, China 4 Institute of Genetics and Development, Chinese Academy of Sciences, Beijing, China * These authors have contributed equally to this work Correspondence to: Xiao-hong Yao, email: yxh15@hotmail.com Xiu-wu Bian, email: bianxiuwu@263.net Keywords: chemosensitivity, collagen scaffold, glioma stem cells, three-dimensional culture, MGMT Received: February 27, 2016      Accepted: June 30, 2016      Published: July 28, 2016 ABSTRACT Three-dimensional (3D) culture, which can simulate in vivo microenvironments, has been increasingly used to study tumor cell biology. Since most preclinical anti-glioma drug tests still rely on conventional 2D cell culture, we established a collagen scaffold for 3D glioma cell culture. Glioma cells cultured on these 3D scaffolds showed greater degree of dedifferentiation and quiescence than cells in 2D culture. 3D-cultured cells also exhibited enhanced resistance to chemotherapeutic alkylating agents, with a much higher proportion of glioma stem cells and upregulation of O6-methylguanine DNA methyltransferase (MGMT). Importantly, tumor cells in 3D culture showed chemotherapy resistance patterns similar to those observed in glioma patients. Our results suggest that 3D collagen scaffolds are promising in vitro research platforms for screening new anti-glioma therapeutics.