4.7 Article

A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment

Journal

NPJ PRECISION ONCOLOGY
Volume 6, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41698-022-00290-8

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Funding

  1. National Institutes of Health National Cancer Institute [R37 CA222563]
  2. National Institutes of Health National Institute of General Medical Sciences [R01 GM140042]
  3. Coulter Foundation
  4. NCI Training Grant [T32 CA009109]
  5. University of Virginia Harrison Undergraduate Research Award
  6. National Science Foundation [MCB-1517506]
  7. Virginia Tech ICTAS-CEH

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In this study, a four-component 3D model of glioblastoma was created using patient-derived glioma stem cells and human glial cells. The model allowed examination of invasion, proliferation, and stemness in the context of glial cells, fluid forces, and chemotherapies. The findings suggest that interstitial flow promotes glioma cell proliferation and stemness, while glial cells affect invasion and stemness, potentially through CCL2 expression and differential activation.
Glioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We use patient-derived glioma stem cells and human glial cells (i.e., astrocytes and microglia) to create a four-component 3D model of this environment informed by resected patient tumors. We examine metrics for invasion, proliferation, and putative stemness in the context of glial cells, fluid forces, and chemotherapies. While the responses are heterogeneous across seven patient-derived lines, interstitial flow significantly increases glioma cell proliferation and stemness while glial cells affect invasion and stemness, potentially related to CCL2 expression and differential activation. In a screen of six drugs, we find in vitro expression of putative stemness marker CD71, but not viability at drug IC50, to predict murine xenograft survival. We posit this patient-informed, infiltrative tumor model as a novel advance toward precision medicine in glioblastoma treatment.

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