Vascularization ability of glioma stem cells in different three-dimensional microenvironments

Area of Science:

• Biomedical Engineering
• Oncology
• Regenerative Medicine

Background:

• Glioblastoma (GBM) is an aggressive brain tumor characterized by abnormal microvessels and angiogenesis.
• Tumor angiogenesis significantly correlates with GBM prognosis.
• Developing accurate in vitro models for GBM neovascularization is crucial for anti-angiogenic therapy research.

Purpose of the Study:

• To investigate glioma stem cell (GSC) vascularization in different 3D microenvironments using bioprinted scaffolds.
• To assess the suitability of 3D bioprinted GSC-laden hydrogel scaffolds for modeling the glioma microenvironment and tumor angiogenesis.

Main Methods:

• Manufactured 3D bioprinted GSC-laden hydrogel scaffolds, hybrid GSC hydrogels, and cell-free hydrogel scaffolds.
• Assessed GSC bioactivity and growth factor production in varying 3D microenvironments.
• Co-cultured models with human umbilical vein endothelial cells to evaluate angiogenesis markers.
• Generated xenograft tumors from bioprinted scaffolds for comparison with human gliomas.

Main Results:

• 3D bioprinted GSC-laden hydrogel scaffolds showed preferable and stable GSC bioactivity.
• Highest levels of vascular endothelial growth factor A and basic fibroblast growth factor were found in the bioprinted scaffold microenvironment.
• Bioprinted scaffolds exhibited the most abundant expression of angiogenesis markers upon co-culture with endothelial cells.
• Xenograft tumors from bioprinted scaffolds closely resembled human gliomas in color, texture, and vascularization, with increased human CD105+ cells and vascular lumen formation.

Conclusions:

• The 3D bioprinted GSC-laden hydrogel scaffold is a suitable model for mimicking the glioma microenvironment.
• This model effectively supports the study of tumor angiogenesis in glioblastoma.
• The findings support the development of novel anti-angiogenic therapies for GBM.