Culture on 3D Chitosan‐Hyaluronic Acid Scaffolds Enhances Stem Cell Marker Expression and Drug Resistance in Human Glioblastoma Cancer Stem Cells. Issue 24 (2nd November 2016)

• Record Type: Journal Article
• Authors: Wang, Kui; Kievit, Forrest M.; Erickson, Ariane E.; Silber, John R.; Ellenbogen, Richard G.; Zhang, Miqin
• Is Part Of: Advanced healthcare materials. Volume 5:Issue 24(2016)
• Page Start: 3173
• Page End: 3181
• Publication Date: 2016-11-02
• Subjects: chitosan -- drug resistance -- glioblastoma stem cell -- hyaluronic acid -- scaffold; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201600684
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract : The lack of in vitro models that support the growth of glioblastoma (GBM) stem cells (GSCs) that underlie clinical aggressiveness hinders developing new, effective therapies for GBM. While orthotopic patient‐derived xenograft models of GBM best reflect in vivo tumor behavior, establishing xenografts is a time consuming, costly, and frequently unsuccessful endeavor. To address these limitations, a 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) is synthesized. Growth and expression of the cancer stem cell (CSC) phenotype of the GSC GBM6 taken directly from fresh xenogratfs grown on scaffolds or as adherent monolayers is compared. While 2D adherent cultures grow as monolayers of flat epitheliod cells, GBM6 cells proliferate within pores of CHA scaffolds as clusters of self‐adherent ovoid cells. Growth on scaffolds is accompanied by greater expression of genes that mediate epithelial–mesenchymal transition and maintain a primitive, undifferentiated phenotype, hallmarks of CSCs. Scaffold‐grown cells also display higher expression of genes that promote resistance to hypoxia‐induced oxidative stress. In accord, scaffold‐grown cells show markedly greater resistance to clinically utilized alkylating agents compared to adherent cells. These findings suggest that our CHA scaffolds better mimic in vivo biological and clinical behavior and provide insights for developing novel individualized treatments. Abstract : A 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) can support the growth of glioblastoma stem cells harvested from tumor tissue. The CHA culture promotes expression of genes that mediate epithelial–mesenchymal transition and represent hallmarks of cancer stem cells. Scaffold‐grown cells also have greater resistance to clinically utilized alkylating agents when compared to adherent cells cultured on 2D.