Based on the implantation of human GBM-derived spheroid cultures, we have generated clinically-relevant mouse models that recapitulate the major characteristics associated with GBMs including angiogenesis and tumor invasion.
The tumour xenografts obtained in these animals appear either angiogenic – displaying abnormal blood vessels, or highly invasive, depending on the patient’s GBMs used for implantation. In order to study how tumors are communicating with the host cells, we have also developed immunodeficient eGFP expressing mouse models that allow us to study in detail how the tumors are communicating with the host cells.
These models greatly facilitate the dissection of the biological mechanisms behind angiogenesis and tumor invasion and represent important tools for clinically relevant therapeutic intervention studies, which are crucial for developing novel treatment strategies.
Tumour resection xenograft model
The GBM animal models, previously described above, allows us to study the tumour bulk. However, it does not represent the clinical situation following surgery that most patients undergo, with subsequent adjuvant radiotherapy and concomitant chemotherapy. Thus, therapeutic studies on brain tumours should optimally take into consideration the tumour cells that are left behind after surgery, i.e those cells we are unable to remove, and that infiltrate the surrounding parenchyma, eventually giving rise to tumour recurrence. To address these limitations we are currently establishing a novel model that mimics the setting after surgical resection in GBM patients. This method involves implantation of human GBM tissue followed by resection of the resulting tumour, cranial defect repair and monitoring of tumour recurrence using MRI and animal PET/CT scans. Moreover, because of the cranial defect repair, the isolation of the surgical resection cavity from direct continuation with the subgaleal space allows the animals can be treated by cytotoxic agents with directly intracavity delivery.
The image shows the MRI scans: tumour pre-resection (far left) vs post-resection at day 3(to the right), day 7(g), and day 11(h) showing tumour recurrence (dashed area). White arrow head show the absorbable “surgicel”.