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Updated: Feb 18, 2026
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Three-Dimensional In Vitro Biomimetic Model of Neuroblastoma Using Collagen-Based Scaffolds
Published on: July 9, 2021
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Vascularized Tissue-Engineered Model for Studying Drug Resistance in Neuroblastoma
A Villasante1,2, K Sakaguchi3, J Kim1
1Laboratory for Stem Cells and Tissue Engineering, Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Theranostics
|November 22, 2017
Summary
This study developed a 3D neuroblastoma model to investigate retinoid therapy. Isotretinoin failed to target cancer stem-like cells (CSLCs) and their vasculogenic mimicry, highlighting SOX2 as a potential therapeutic target.
Area of Science:
- Oncology
- Biomedical Engineering
- Developmental Biology
Background:
- Neuroblastoma is a pediatric cancer with high relapse rates, driven by cancer stem-like cells (CSLCs) with drug-resistance and plasticity.
- Vasculogenic mimicry and stemness markers like SOX2 and NANOG are key features of neuroblastoma.
- Current limitations in modeling human neuroblastoma hinder therapeutic development.
Purpose of the Study:
- To engineer a perfusable, vascularized 3D *in vitro* model of human neuroblastoma.
- To investigate the effects of retinoid therapy on neuroblastoma vasculature and drug-resistance using this model.
Main Methods:
- A 3D neuroblastoma model was created using cell-sheet engineering and a perfusion bioreactor.
- The model incorporated SKNBE(2) neuroblastoma cells, HUVECs, and a fibrin-collagen vascular bed with microchannels.
- Models were treated with isotretinoin (10μM) for 5 days.
Main Results:
- The engineered model successfully recapitulated vasculogenic mimicry and CSLC markers (SOX2, NANOG).
- Isotretinoin treatment destabilized tumor vasculature but did not inhibit vasculogenic mimicry.
- CSLC populations increased with SOX2 expression, suggesting transdifferentiation into drug-resistant CD31+ TECs (stem tumor-derived endothelial cells).
Conclusions:
- SOX2 plays a role in neuroblastoma drug resistance and relapse.
- CSLCs may transdifferentiate into drug-resistant endothelial cells, contributing to treatment failure.
- SOX2 is a potential therapeutic target for neuroblastoma.
