Patient-specific ex vivo models of human tumours that recapitulate the pathological characteristics and complex ecology of native tumours could help determine the most appropriate cancer treatment for individual patients. Here, we show that bioprinted reconstituted glioblastoma tumours consisting of patient-derived tumour cells, vascular endothelial cells and decellularized extracellular matrix from brain tissue in a compartmentalized cancer–stroma concentric-ring structure that sustains a radial oxygen gradient, recapitulate the structural, biochemical and biophysical properties of the native tumours. We also show that the glioblastoma-on-a-chip reproduces clinically observed patient-specific resistances to treatment with concurrent chemoradiation and temozolomide, and that the model can be used to determine drug combinations associated with superior tumour killing. The patient-specific tumour-on-a-chip model might be useful for the identification of effective treatments for glioblastoma patients resistant to the standard first-line treatment.
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The computer code for the bioprinting of the GBM-on-a-chip is provided as Supplementary Information.
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This work was supported by the National Research Foundation of Korea (NRF) funded by the Korean government, MSIP (grant nos 2010-0018294, 2015R1A2A2A01005515 and 2018R1A2B2009540). This study was partly supported by the Technology Innovation Program (grant no. 10050154, Business Model Development for Personalized Medicine Based on Integrated Genome and Clinical Information) and by the Bio and Medical Technology Development Program of the NRF funded by the Korean government, MSIP (grant no. 2015M3C7A1028926). We thank J. M. Hong for technical assistance and M. N. Park for helpful discussions.
Patents on the use of BdECM bioink in modelling cancer (patent no. 10-1860798, Korea) and on 3D printing of GBM-on-a-chip (patent no. 10-1803618, Korea) have been registered.
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Yi, H., Jeong, Y.H., Kim, Y. et al. A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat Biomed Eng 3, 509–519 (2019). https://doi.org/10.1038/s41551-019-0363-x
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