Understanding childhood brain tumours | Replacing Animal Research

The Problem

Diffuse midline gliomas (DMGs) are tumours that occur in the brainstem and are incredibly difficult to access and treat.  

The brainstem acts like the control tower of your body, a vital hub that manages essential life functions like breathing. DMGs are aggressive tumours that take root right in this crucial control tower. Their location in the brainstem makes them incredibly difficult to access and treat, so surgery is impossible. Currently, there’s no other effective treatment.

These highly aggressive childhood tumours are most commonly diagnosed in children between the ages of six and nine. 95% of children die within two years of diagnosis.

Studying these complex tumours has always posed a huge challenge. DMGs are difficult to grow in traditional 2D cultures, so researchers have relied on animal ‘models’. This involves injecting tumour cells into the brainstem, specifically, a part called the pons, of animals.

It’s a highly invasive procedure with many unintended consequences. Over 20% of animals are lost due to procedural severity or tumour rejection before the research even begins.

However, advancements are being made. Professor Coyle’s team have already made significant strides forward. They have developed a special ‘brain hydrogel model’. Think of this hydrogel as a sophisticated, jelly-like scaffold designed to mimic the brain’s environment.

They’ve already shown that two other types of paediatric brain tumours can grow well within this hydrogel. The next crucial step is testing it with Diffuse Midline Gliomas.

The Project

Emily’s project aims to see if Diffuse Midline Gliomas cells can thrive within Professor Coyle’s hydrogel-based 3D models. If they can, this innovative approach would allow scientists to investigate the mechanisms that drive these tumours to grow and spread.

She plans to compare the characteristics of two different cell lines. This will allow her to see whether the specific genetic mutation they carry affects their ability to grow and invade surrounding tissue. She’ll also investigate whether the presence of our body’s natural defenders, immune cells, impacts the tumours’ progression.

Growing these tumour cells in a 3D environment, embedded in the hydrogel, could be a game-changer. This approach will help establish:

If this model can be more cost-effective.

If the model could provide a more accurate alternative to animal ‘models’.

The Potential

If all goes to plan, the development of a fully humanised, truly representative 3D model for Diffuse Midline Gliomas will have a significant impact. It will deepen our understanding of precisely how these aggressive tumours grow and invade, giving us vital clues on how to stop them.

Ultimately, this pioneering work will hopefully empower many other research groups around the world. By significantly increasing the possibility of finding an effective treatment for this devastating disease, Emily’s research offers a brighter future for children diagnosed with DMGs, all without the use of animals.

The update

In the lab, Emily managed to grow cells derived from diffuse midline gliomas from two different patients. By growing them in different conditions in both 2D and 3D, she found that the different mutations carried by the cancer cells ultimately control how the tumours develop and spread.

She cultured the tumour cells in a 3D using a bespoke hydrogel, and incubated them with and without immune cells isolated from the blood of a healthy volunteer.

By using fluorescence microscopy techniques, Emily found that one cell line showed rapid, diffuse proliferation but was unstable when grown on its own in hydrogel in 3D. Co-culturing them with immune cells seemed to encourage growth, implying that the cancer responds positively to substances released by immune cells.

Emily then found that the cell line from the second patient grew more slowly, forming compact clusters and appeared to migrate towards the immune cells when grown in the hydrogel models.

Together, these results highlight that both tumour genotype and microenvironment influence shape growth and behaviour, and how the inclusion of immune cells are vital to model this difficult to treat cancer in the lab. This supports Emily and Professor Coyle’s aim of including immune cells into the models.

By progressing from 2D culture to 3D spheroids and hydrogels, Emily showed the strengths and limitations of increasingly complex in vitro systems in developing physiologically relevant models for cancer research.