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

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dc.contributor.authorCornelison, R. Chaseen
dc.contributor.authorYuan, J. X.en
dc.contributor.authorTate, Kinsley M.en
dc.contributor.authorPetrosky, A.en
dc.contributor.authorBeeghly, G. F.en
dc.contributor.authorBloomfield, Mathewen
dc.contributor.authorSchwager, S. C.en
dc.contributor.authorBerr, A. L.en
dc.contributor.authorStine, Caleb A.en
dc.contributor.authorCimini, Danielaen
dc.contributor.authorBafakih, F. F.en
dc.contributor.authorMandell, J. W.en
dc.contributor.authorPurow, B. W.en
dc.contributor.authorHorton, B. J.en
dc.contributor.authorMunson, Jennifer M.en
dc.date.accessioned2022-08-03T16:58:56Zen
dc.date.available2022-08-03T16:58:56Zen
dc.date.issued2022-07-29en
dc.description.abstractGlioblastoma 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41698-022-00290-8en
dc.identifier.urihttp://hdl.handle.net/10919/111439en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Portfolioen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCancer modelsen
dc.subjectCancer stem cellsen
dc.subjectCNS canceren
dc.subjectPredictive markersen
dc.subjectTranslational researchen
dc.titleA patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironmenten
dc.title.serialnpj Precision Oncologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Biomedical Engineering and Mechanics
Destination Area: Adaptive Brain and Behavior (ABB)
Scholarly Works, Biological Sciences
Scholarly Works, Fralin Biomedical Research Institute at VTC
Scholarly Works, Fralin Life Sciences Institute