PNJ scaffolds promote microenvironmental regulation of glioblastoma stem-like cell enrichment and radioresistance

John M. Heffernan, James B. McNamara, Brent L. Vernon, Shwetal Mehta, Rachael W. Sirianni

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma (GBM) brain tumors contain a subpopulation of self-renewing multipotent Glioblastoma stem-like cells (GSCs) that are believed to drive the near inevitable recurrence of GBM. We previously engineered temperature responsive scaffolds based on the polymer poly(N-isopropylacrylamide-co-Jeffamine M-1000 acrylamide) (PNJ) for the purpose of enriching GSCs in vitro from patient-derived samples. Here, we used PNJ scaffolds to study microenvironmental regulation of self-renewal and radiation response in patient-derived GSCs representing classical and proneural subtypes. GSC self-renewal was regulated by the composition of PNJ scaffolds and varied with cell type. PNJ scaffolds protected against radiation-induced cell death, particularly in conditions that also promoted GSC self-renewal. Additionally, cells cultured in PNJ scaffolds exhibited increased expression of the transcription factor HIF2α, which was not observed in neurosphere culture, providing a potential mechanistic basis for differences in radio-resistance. Differences in PNJ regulation of HIF2α in irradiated and untreated conditions also offered evidence of stem plasticity. These data show PNJ scaffolds provide a unique biomaterial for evaluating dynamic microenvironmental regulation of GSC self-renewal, radioresistance, and stem plasticity.

Original languageEnglish (US)
Pages (from-to)819-833
Number of pages15
JournalBiomaterials Science
Volume10
Issue number3
DOIs
StatePublished - Feb 7 2022

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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