Towards validation of clinical relevance of 3D in vitro models in brain tumour research

The Problem

Brain tumours, especially gliomas, make up 25% of childhood cancers. Gliomas are a type of brain tumour that starts in the glial cells, the supporting cells of the brain and spinal cord. One particularly aggressive type of glioma is Glioblastomas, which are high-grade tumours and the most common type of glioma in children and adults.

Brain tumour research tends to centre on the use of animal ‘models’. However, there’s a lack of solid comparisons between these animal ‘models’ and the results obtained from in vitro models.

Sophie was one of two of our Summer students working on glioblastoma this year. Her project involved growing mini glioblastoma tumours as ‘spheroids’ in the lab, which allows the extent of cell migration, or their ability to invade the brain, to be seen and measured, which helps determine the effectiveness of potential anti-migratory drugs.

Imagine a map showing how a city might grow. Researchers often use animal ‘models’ to study how tumours spread in the brain. Sophie’s work involved creating tiny, 3D models of tumours in the lab to map how cancer cells move and spread within these models. This helps scientists understand how tumours behave and test potential treatments.

The Project

She created mini brain tumours, or spheroids, with an engineered reduced or enhanced ability to navigate through the brain environment. These ‘tumours’ were allowed to invade an artificial brain environment created in the lab, and the invasive behaviour of these tumours was studied by high-resolution microscopy.

The results were compared to archival experimental data from brain scans from mice given the same cells used for the spheroids.

Sophie managed to grow 3D spheroids from three human glioblastoma cell lines and found them all showing the migratory behaviour she expected due to their genetic engineering. This migratory behaviour mimics the invasive nature of different types of glioblastoma seen in patients.

She then used confocal microscopy, which allows 3D images to be taken, and analysed the migratory behaviour of the mini-brain tumours using Cloudbuster V2 software and compared this to the MRI scans from the historical mouse experiments.

She saw that the measurements for the protrusions from the invasive cells in her spheroids were the same as in the mouse MRIs. However, in her model, individual cells could be identified which was not the case on the corresponding MRI images.

The Potential

Sophie found that the MRI from the mouse studies did not give the same resolution she saw from her spheroid models. MRI scans are known to have low resolution where ‘microtumours’ and single cells are concerned, and this means that small spreading tumours which are common in cancer patients can be easily missed.

By comparing this new in vitro model with data from historic animal studies Sophie is providing evidence that non-animal-based technologies, can directly replace the use of mice in glioblastoma research and help other researchers make the transition towards non-animal methods themselves.