Rapid and Efficient Invasion Assay of Glioblastoma in Human Brain Organoids

Gladiola Goranci-Buzhala, Aruljothi Mariappan, Elke Gabriel, Anand Ramani, Lucia Ricci-Vitiani, Mariachiara Buccarelli, Quintino Giorgio D'Alessandris, Roberto Pallini, Jay Gopalakrishnan

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Glioblastoma (GBM) possesses glioma stem cells (GSCs) that exhibit aggressive invasion behavior in the brain. Current preclinical GBM invasion assays using mouse brain xenografts are time consuming and less efficient. Here, we demonstrate an array of methods that allow rapid and efficient assaying of GSCs invasion in human brain organoids. The assays are versatile to characterize various aspects of GSCs, such as invasion, integration, and interaction with mature neurons of brain organoids. Tissue clearing and quantitative 3D imaging of GSCs in host organoids reveal that invasiveness is inversely correlated with the organoids' age. Importantly, the described invasion assays can distinguish the invasive behaviors of primary and recurrent GSCs. The assays are also amenable to test pharmacological agents. As an example, we show that GI254023X, an inhibitor of ADAM10, could prevent the integration of GSCs into the organoids.
Lingua originaleEnglish
pagine (da-a)107738-N/A
RivistaCell Reports
Volume31
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • 3D human brain organoids
  • ADAM10 inhibitor
  • Brain
  • GBM
  • Glioblastoma
  • Humans
  • NGLN3
  • Organoids
  • glioma invasion
  • glioma stem cells
  • iPSCs
  • imaging
  • tissue clearing

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