Bioprinting of glioma stem cells improves their endotheliogenic potential.

Abstract

Glioblastoma (GBM), with rich blood vessels and high invasiveness, is the most common malignant primary brain tumor. The current treatment strategies are less effective, resulting in tumor recurrence. Tumor angiogenesis plays an important role in the occurrence, development and metastasis of GBM. Currently, GBM has been treated by inhibiting tumor angiogenesis. In-depth study of tumor angiogenesis is of great significance for the treatment of GBM. Recent studies have shown that glioma stem cells (GSCs) are involved in tumor vascularization by secreting vascular endothelial growth factor (VEGF). It is necessary to construct an ideal in vitro model to study the mechanism of GSCs in tumor vascularization. Here we used extrusion-based three-dimensional (3D) bioprinting technology to fabricate GSCs tumor model. In this study, the viability of cells after bioprinting was 86.27 ± 2.41%. Furthermore, compared with traditional suspension culture, the proliferation of 3D printed GSCs was more stable. Through the transmission electron microscopy (TEM), numerous long microvilli of cells cultured in 3D bioprinted scaffolds were observed. 3D bioprinted GSCs also have more abundant mitochondria and rough endoplasmic reticulum. Additionally, the stemness properties, the expression of tumor angiogenesis-related genes and vascularization potential of 3D bioprinted GSCs in vitro were higher than that of suspension cultured cells. In summary, 3D bioprinted cell-laden hydrogel scaffolds provide a proper model for investigating the biological characteristics of GSCs and tumor angiogenesis.