Three-Dimensional, Scaffolded Tumor Model to Study Cell-Driven Microenvironment Effects and Therapeutic Responses

Area of Science:

• Biomedical Engineering
• Oncology
• Biomaterials Science

Background:

• Traditional 2D cell cultures fail to accurately represent in vivo tumor microenvironments.
• Developing novel therapeutics for neuroblastoma is hindered by limitations in current preclinical models.

Purpose of the Study:

• To develop and characterize a 3D neuroblastoma model using silk fibroin scaffolds.
• To investigate the impact of oxygen levels and scaffold architecture on neuroblastoma behavior.
• To evaluate the efficacy of chemotherapeutics in 3D versus 2D models.

Main Methods:

• Lyophilized silk fibroin scaffolds were used to culture neuroblastoma cell lines (SK-N-AS, KELLY, SH-SY5Y).
• Cells were cultured under low (1%) and ambient (21%) oxygen conditions.
• Gene expression, cytokine secretion, and drug cytotoxicity were analyzed and compared between 3D scaffolded and 2D monolayer cultures.

Main Results:

• Scaffold-based 3D neuroblastoma models exhibited increased expression of hypoxia-related genes under both low and ambient oxygen.
• Differential cytokine secretion patterns were observed in 3D cultures compared to 2D cultures.
• Scaffolded neuroblastoma showed reduced sensitivity to etoposide but increased sensitivity to tirapazamine under specific oxygen conditions.

Conclusions:

• Silk fibroin scaffolds provide a more physiologically relevant 3D model for neuroblastoma research.
• This 3D culture system allows for the study of hypoxia's role in neuroblastoma.
• The model aids in evaluating novel therapeutics targeting neuroblastoma and its tumor microenvironment.