Project overview

The major aims of the present research project are to elaborate on the similarities between GSC niches and HSC niches to increase sensitivity to radiotherapy and chemotherapy of GSCs in their niches. For that purpose, we want to address the following 4 major research questions:

  1. Are NSC and GSC niches functionally similar to HSC niches? We want to investigate whether

NSC niches that are present in the SVZ in normal human brain are the missing link between HSC niches and GSC niches. It will also be investigated whether NSC niches in the SVZ are hijacked by GSCs using the SDF-1α-CXCR4 axis just like HSC niches in human bone marrow are hijacked by LSCs in hematological malignancies. If this is the case, clinical trials using plerixafor to mobilize LSCs from HSC niches before chemotherapy can be performed to treat glioblastoma patients in combination with standard therapies.

  1. Why are arteriolar walls specifically and uniquely associated with GSC niches in human glioblastoma and HSC niches in bone marrow? As the distance between arteriolar endothelial cells and peri-arteriolar GSCs is too large for direct effects, we want to investigate how indirect effects of arteriolar endothelial cells on GSC niches are exerted. At first instance, we want to elucidate the intermediate role of the thick layer of smooth muscle cells (SMCs) forming the tunica media in the wall of arterioles (Fig. 1). This thick circulatory layer of SMCs is unique for arteries including arterioles. We want to investigate in cocultures of arteriolar endothelial cells and/or SMCs and patient-derived GSCs or differentiated glioblastoma cells what the effects are of these cell types in the arteriolar wall on GSCs. Furthermore, we want to investigate whether tunneling nanotubes (TNTs) and/or tumor microtubes (TMs) play a role in communication between on the one hand endothelial cells and SMCs and GSCs on the other.
  2. Can plerixafor be administered to glioblastoma patients to mobilize GSCs from their niches before radiotherapy or chemotherapy? We will test the effects of plerixafor on GSCs in vitro in co-cultures with essential cell types that are part of the microenvironment of GSC niches. Since GSC niches are exclusively peri-arteriolar in glioblastoma tumors, transwell assays will be used to mimic the peri-arteriolar GSC niche. GSCs will be cultured in the inserts in the presence or absence of plerixafor and a co-culture of arteriolar endothelial cells and SMCs will be grown in the bottom wells.
  3. Are the specific signaling pathways that are known to be essential and specific for the formation and maintenance of arteriolar walls, Shh, VEGF and Notch involved in the maintenance of GSC stemness? We want to study the effects of these signaling pathways on maintenance of GSCs and dedifferentiation of glioblastoma cells.


We are open for collaborations, if you’re interested please contact Prof. Cornelis J.F. Van Noorden, PhD