Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM.
Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM.
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DOI：
10.1016/j.biomaterials.2013.09.034
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发表时间：
2013-12
期刊：
影响因子：
14
通讯作者：
Zhang, Miqin
中科院分区：
文献类型：
--
作者：
Florczyk, Stephen J.;Wang, Kui;Jana, Soumen;Wood, David L.;Sytsma, Samara K.;Sham, Jonathan G.;Kievit, Forrest M.;Zhang, Miqin
癌症治疗方法是通过广泛的筛选发展起来的;然而，在临床前试验中，许多用2D体外培养评估的治疗方法对患者的疗效较低。利用三维（3D）多孔支架在体外复制体内肿瘤微环境，为生成更具预测性的临床前模型提供了可能，从而提高癌症治疗效果。制备了壳聚糖和透明质酸（HA）聚电解质复合物三维多孔支架，并对其物理性能进行了评价。壳聚糖-透明质酸（C-HA）支架具有高度多孔的网络。将C-HA支架与体外培养U-118 MG人胶质母细胞瘤（GBM）细胞的二维表面进行比较。与2D培养相比，C-HA支架培养促进了肿瘤球体的形成，增加了GBM细胞的干样特性，CD44、Nestin、Musashi-1、GFAP和HIF-1α的上调证明了这一点。此外，在C-HA支架中培养的GBM细胞的侵袭性与在2D培养中培养的细胞相比显著增强。C-HA支架培养物对化疗药物的耐药性也更强，这与ABCG2药物外排转运蛋白的表达增加相对应。这些发现表明，C-HA支架有望作为研究和筛选新型癌症治疗方法的体外GBM平台。
Cancer therapeutics are developed through extensive screening; however, many therapeutics evaluated with 2D in vitro cultures during pre-clinical trials suffer from lower efficacy in patients. Replicating the in vivo tumor microenvironment in vitro with three-dimensional (3D) porous scaffolds offers the possibility of generating more predictive pre-clinical models to enhance cancer treatment efficacy. We developed a chitosan and hyaluronic acid (HA) polyelectrolyte complex 3D porous scaffold and evaluated its physical properties. Chitosan-HA (C-HA) scaffolds had a highly porous network. C-HA scaffolds were compared to 2D surfaces for in vitro culture of U-118 MG human glioblastoma (GBM) cells. C-HA scaffold cultures promoted tumor spheroid formation and increased stem-like properties of GBM cells as evidenced by the upregulation of CD44, Nestin, Musashi-1, GFAP, and HIF-1α as compared with 2D cultures. Additionally, the invasiveness of GBM cells cultured in C-HA scaffolds was significantly enhanced compared to those grown in 2D cultures. C-HA scaffold cultures were also more resistant to chemotherapy drugs, which corresponded to the increased expression of ABCG2 drug efflux transporter. These findings suggest that C-HA scaffolds offer promise as an in vitro GBM platform for study and screening of novel cancer therapeutics.
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DOI：
10.1073/pnas.0808932106
发表时间：
2009-01-13
影响因子：
11.1
作者：
Fischbach, Claudia;Kong, Hyun Joon;Mooney, David J.
通讯作者：
Mooney, David J.
影响因子：
4.1
作者：
Chua, Constance;Zaiden, Norazean;Tang, Carol
通讯作者：
Tang, Carol
影响因子：
14
作者：
Ananthanarayanan, Badriprasad;Kim, Yushan;Kumar, Sanjay
通讯作者：
Kumar, Sanjay
影响因子：
10
作者：
Florczyk, Stephen J.;Liu, Gang;Kievit, Forrest M.;Lewis, Allison M.;Wu, Jennifer D.;Zhang, Miqin
通讯作者：
Zhang, Miqin
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM