Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model

Wenjing Zhou, Frits A. Thorsen, Konrad Grützmann, Boris Mihaljevic, Barbara van Loon, Jubayer A. Hossain, Anna Golebiewska, Simone Niclou, Magnar Bjørås, Saverio Tardito, Justin Vareecal Joesph, Elena Martinez-Garcia, Taral R. Lunavat, Halala Sdik Saed, Marzieh Bahador, Minghzi Han, Carina Fabian, Hrvoje Miletic, Xingang Li, Jian WangGunnar Dittmar, Olivier Keunen, Katharina Sarnow, Barbara Klink, Rolf Bjerkvig, Georgia Kanli, Petr Nazarov, Stephanie G. Schwab, Johannes Meiser, Christian Jäger, Jakub Mieczkowski

Research output: Working paperPreprint

Abstract

To model neurological diseases using brain organoids (BOs), there is a need for the development of terminally differentiated structures that reflect the structural and cellular complexity of mature brain tissue. Here we describe the developmental path of rat brain organoids (rBOs) into terminally differentiated brain structures. These organoids were compared to BOs derived from induced human pluripotent stem cells (iPSC) at the transcriptomic, proteomic and metabolomic level, showing that the rBOs present a higher degree of brain maturation. We further show that the rBOs can be used as an  ex vivo  avatar co-culture system to decipher important glioblastoma invasion parameters such as invasive cellular heterogeneity between patient-derived glioblastoma cells where key invasion parameters such as speed of single cell invasion and replacement of brain tissue by tumor cells can be measured and quantified in real-time. Finally, we show how this model can be used to assess therapeutic interventions, among others, directed toward neuro-gliomal α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor communication.
Original languageEnglish
DOIs
Publication statusSubmitted - 15 Nov 2022

Publication series

NameDEVELOPMENTAL-CELL-D-22-00801

Keywords

  • Brain organoids
  • glioblastoma
  • invasion
  • inhibition

Fingerprint

Dive into the research topics of 'Deciphering Human Glioblastoma Invasion Using a Developmental Mature Rat Brain Organoid Model'. Together they form a unique fingerprint.

Cite this