Cancer stem cells (CSCs), being
tumor-initiating with self-renewal capacity and heterogeneity, are most likely the cause of
tumor resistance, reoccurrence and
metastasis. To further investigate the role of CSCs in
tumor biology, there is a need to develop an effective culture system to grow, maintain and enrich CSCs. Three-dimensional (3D) cell culture model has been widely used in
tumor research and drug screening. Recently, researchers have begun to utilize 3D models to culture
cancer cells for CSCs enrichment. In this study,
glioma cell line was cultured with 3D porous
chitosan (CS) scaffolds or
chitosan-
hyaluronic acid (CS-HA) scaffolds to explore the possibility of
glioma stem cells (GSCs)-like cells enrichment, to study the morphology, gene expression, and in vivo tumorigenicity of 3D scaffolds cells, and to compare results to 2D controls. Results showed that
glioma cells on both CS and CS-HA scaffolds could form
tumor cell spheroids and increased the expression of GSCs
biomarkers compared to conventional 2D monolayers. Furthermore, cells in CS-HA scaffolds had higher expression levels of epithelial-to-mesenchymal transition (EMT)-related gene. Specifically, the in vivo tumorigenicity capability of CS-HA scaffold cultured cells was greater than 2D cells or CS scaffold cultured cells. It is indicated that the chemical composition of scaffold plays an important role in the enrichment of CSCs. Our results suggest that CS-HA scaffolds have a better capability to enrich GSCs-like cells and can serve as a simple and effective way to cultivate and enrich CSCs in vitro to support the study of CSCs biology and development of novel anti-
cancer therapies.