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Updated: Oct 7, 2025
Three-Dimensional In Vitro Biomimetic Model of Neuroblastoma Using Collagen-Based Scaffolds
Published on: July 9, 2021
Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing
Dongwei Wu1, Johanna Berg1, Birte Arlt2
1Institute of Biotechnology, Chair of Applied Biochemistry, Technische Universität Berlin, 13355 Berlin, Germany.
Abstract:
Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.
Insights
This study introduces a novel 3D bioprinted neuroblastoma model using human cells. This advanced model accurately predicts drug efficacy and selectivity, improving anticancer drug development for pediatric cancers.
Area of Science:
- Oncology
- Biotechnology
- Drug Development
Background:
- Current animal models for anticancer drug development are limited by animal-derived environments, hindering human cancer cell studies.
- Neuroblastoma, a common childhood cancer, presents challenges due to chemotherapy resistance and relapses, particularly in high-risk patients.
Purpose of the Study:
- To develop a novel, fully human three-dimensional (3D) bioprinted model for neuroblastoma research.
- To assess the efficacy and selectivity of anticancer drugs using this new human-derived 3D model.
Main Methods:
- A 3D neuroblastoma model was created using IMR-32 cells (amplified MYCN and ALK genes) within a human renal microenvironment (HEK 293 cells and primary fibroblasts).
- Pneumatic extrusion bioprinting technology was employed to construct the 3D model.
- The model was used to test the effects of panobinostat and blasticidin on cancer and renal cells.
Main Results:
- Panobinostat selectively induced apoptosis in neuroblastoma cells without affecting renal cells at therapeutic concentrations.
- Blasticidin caused cell death in both cancer and renal cells.
- Drug sensitivity varied between 2D and 3D cultures, indicating a broader therapeutic window in the bioprinted model.
Conclusions:
- The developed human 3D bioprinted neuroblastoma model is valuable for testing the cytotoxicity and tumor selectivity of novel anticancer drugs.
- This model demonstrates the importance of studying drug responses in human-specific 3D environments, offering a more accurate preclinical assessment.
- The open scaffold design facilitates future modifications for diverse tumor and microenvironment studies.
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