Aug 20, 2021

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

Posted by in categories: bioengineering, biotech/medical, genetics, neuroscience

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.

Cancer is the second leading cause of death globally. It is estimated that around 30 to 40% of patients with cancer are being treated with ineffective drugs ; therefore, preclinical drug screening platforms attempt to overcome this challenge. Several approaches, such as whole-exome or RNA sequencing (RNA-seq), aim to identify druggable, known mutations or overexpressed genes that may be exploited as a therapeutic target for personalized therapy. More advanced approaches offer to assess the efficacy of a drug or combinations of drugs in patient-derived tumor xenograft models or in vitro three-dimensional (3D) organoids. Unfortunately, most of the existing methods face unmet challenges, which limit their efficacy. For instance, cells can become quiescent or acquire somatic mutations while growing many generations on plastic under the influence of static mechanical forces and in the absence of functional vasculature.

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