Establishing the novel ex-vivo focal demyelination model of Multiple Sclerosis in other laboratories to reduce and replace live animal use

Why did we fund this project?

This award aims to replace the use of mice in multiple sclerosis (MS) research using slices of brain or spinal cord tissue in a focal lesion ex vivo model.

MS is modelled in rodents by immunising against myelin, causing the immune system to target the myelin that insulates axons. This induces experimental autoimmune encephalomyelitis (EAE), which has similar myelin damage to that seen in patients with MS. EAE results in weakness, fore- and hindlimb paralysis and incontinence, although the degree of severity varies between animals. The studies are associated with a high level of suffering and the need for specialist husbandry and care. Ex vivo slice culture methods have previously been developed but these induce demyelination across the full tissue. Dr Ben Newland has developed a method for inducing focal lesions in ex vivo cultured slices, which then include both healthy and diseased tissue similar to the MS disease state in humans. Up to six brain slices and ten spinal cord slices can be isolated from each animal and demyelinating agent administered to the tissue using a cryogel scaffold. Ben and colleagues have previously validated the ex vivo cryogel method by comparing against post-mortem tissue from MS patients.

Ben will transfer this ex vivo method to the laboratories of Dr Yvonne Dombrowski and Professor Denise Fitzgerald at Queen’s University Belfast. He will also create detailed protocols and training videos to enable other researchers to take up the method. The cryogel scaffolds can be synthesised with a micro-stereolithography based 3D printer and will be made open source to enable easier manufacturing. Ben’s laboratory will also supply cryogels to research groups unable to produce the scaffolds themselves.

• NC3Rs International 3Rs Prize - Highly commended

Ben describes the cryogels and the basic concept of how they can be used on his YouTube channel, how Prof. Anna Williams' team have set up a new model of Multiple Sclerosis, and inviting new collaborations as a tool for delivering reagents or therapeutics locally to tissue in culture.