Project phases and realisation

Our experimental setup of this research project enables the elucidation of novel therapeutic targets in glioblastoma patients on the basis of similarities between GSC niches in glioblastoma tumors and HSC niches in bone marrow.

We have formulated the following hypotheses on the basis of our 4 major aims of the study:

  1. The SVZ in non-cancerous human brain is the missing link between GSC niches in glioblastoma tumors and HSC niches in bone marrow.
  2. The hypoxic tunica adventitia of the arteriolar wall is the place to be for GSCs and HSCs to maintain their stemness in their protecting niches.
  3. The CXCR4 inhibitor plerixafor as adjuvant treatment of glioblastoma patients prior to radiotherapy and/or chemotherapy releases GSCs out of their niches and render them more vulnerable to the standard therapies.
  4. The Shh, VEGF and Notch signalling pathways that dictate arteriolar identity as well as GSC/HSC stemness in combination with Wnt signalling and/or NO signalling by endothelial cells via SMCs and/or via TNTs and TMs explain the preference of stem cell niches adjacent to the tunica adventitia of arterioles.

To test these hypotheses, we will use various in vitro experimental models using patient-derived cells and ex vivo using human tissue samples. The study is organized in 4 work packages (WPs).

WP1: Exploring the SVZ harbouring NSC niches in human non-cancerous brain samples and brain samples that contain glioblastoma tumors (duration: 8 months)

WP2: In a transwell in vitro model, we will explore which cell types of the arteriolar wall are responsible for the maintenance of human GSC/HSC stemness and the induction of glioblastoma cell dedifferentiation (duration: 10 months)

WP3: Exploring whether plerixafor sensitizes GSCs to irradiation (IR) and chemotherapy (duration: 10 months)

WP4: To determine which signalling pathways in the tunica adventitia of the arteriolar wall are essential for GSC/HSC maintenance (duration: 8 months)




Figure: Gantt chart showing the detailed implementation of the research programme proposed in the project.