Journal
SCIENCE ADVANCES
Volume 7, Issue 34, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abi9119
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Funding
- Morris Kahn Foundation
- European Research Council (ERC) [617445]
- ERC [835227]
- ERC Proof of Concept (PoC) Grant [862580]
- Israel Science Foundation [1969/18]
- Israel Cancer Association (ICA) USA [20150909]
- Israel Cancer Research Fund (ICRF) Professorship award [PROF-18-682]
- Check Point Software Technologies Ltd.
- European Research Council (ERC) [862580, 835227] Funding Source: European Research Council (ERC)
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Current cancer models lack tumor-stroma interactions, affecting the proper representation of cancer's complex biology. By creating bioink with patient-derived cells, tumor heterogenic microenvironment can be recapitulated, leading to similar growth curves, drug response, and genetic signature in 3D models compared to traditional 2D cultures. This 3D-bioprinted model has the potential to replace cell cultures and animal models for rapid and robust target discovery, personalized therapy screening, and drug development.
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.
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