Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment
Lena Neufeld1, Eilam Yeini1, Noa Reisman1
1Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Abstract:
Many drugs show promising results in laboratory research but eventually fail clinical trials. We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stroma interactions, which are essential for proper representation of cancer complexed biology. Therefore, we recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells. We observed similar growth curves, drug response, and genetic signature of glioblastoma cells grown in our 3D-bioink platform and in orthotopic cancer mouse models as opposed to 2D culture on rigid plastic plates. Our 3D-bioprinted model could be the basis for potentially replacing cell cultures and animal models as a powerful platform for rapid, reproducible, and robust target discovery; personalized therapy screening; and drug development.
Insights
This study developed a 3D bioprinted glioblastoma model that mimics the tumor microenvironment. This advanced cancer model shows promise for improving drug development and personalized therapy screening.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Tissue Engineering
Background:
- Many cancer drugs fail in clinical trials due to inadequate models that lack tumor-stroma interactions.
- Current 2D cell cultures and animal models do not fully replicate the complex tumor microenvironment.
- Bridging the translational gap requires more sophisticated and representative cancer models.
Purpose of the Study:
- To develop a 3D bioprinted glioblastoma model that recapitulates the tumor microenvironment.
- To create a platform that includes patient-derived cells, stromal components, and perfusable blood vessels.
- To validate the model's ability to mimic glioblastoma biology compared to traditional models.
Main Methods:
- Fabrication of a fibrin glioblastoma bioink with patient-derived glioblastoma cells, astrocytes, and microglia.
- Creation of perfusable blood vessels using sacrificial bioink, brain pericytes, and endothelial cells.
- Comparison of glioblastoma cell growth, drug response, and genetic signature in the 3D model versus 2D cultures and orthotopic mouse models.
Main Results:
- The 3D-bioprinted model successfully recapitulated the heterogeneous tumor microenvironment.
- Glioblastoma cells in the 3D platform exhibited similar growth curves and drug responses as observed in orthotopic mouse models.
- The genetic signature of glioblastoma cells remained consistent between the 3D model and in vivo models, unlike 2D cultures.
Conclusions:
- The developed 3D bioprinted glioblastoma model accurately represents tumor-stroma interactions and cancer biology.
- This platform offers a more robust and reproducible alternative to traditional cell cultures and animal models for cancer research.
- The model holds potential for accelerating target discovery, personalized therapy screening, and drug development in oncology.
