Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment

用于体内模拟肿瘤微环境的微工程可灌注3D生物打印胶质母细胞瘤模型

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作者:Lena Neufeld ,Eilam Yeini ,Noa Reisman ,Yael Shtilerman ,Dikla Ben-Shushan ,Sabina Pozzi ,Asaf Madi ,Galia Tiram ,Anat Eldar-Boock ,Shiran Ferber ,Rachel Grossman ,Zvi Ram ,Ronit Satchi-Fainaro

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.

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