Multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. MS is a debilitating neurological condition that affects 2.5 million patients worldwide. There are currently 142 ongoing MS drug trials to produce products for a market worth $19 billion annually. There is a lack of robust models for testing the effect of drug candidates on myelination.

MYELINATION ASSAY

The Mimetix aligned fibre scaffold supports:

  • the differentiation of more than 80% of oligodendrocyte precursors into mature oligodendrocytes in 14 days
  • myelination – the production of sheath lengths comparable to in vivo situation within 7 days by 90% of the oligodendrocytes
  • the physical guidance and support for Schwann cells

SEM image of the aligned 2 μm diameter PLLA fibres in the Mimetix scaffold

Cortical oligodendrocytes precursors differentiating into active oligodendrocytes and lay myelin on the Mimetix scaffold in the absence of neurons. Cells are stained after 14 days with myelin basic protein (green) and Hoechst (blue).

Percent of oligodendrocyte precursors (NG2) and oligodendrocytes (MBP). More than 600 cells were counted per condition. Mean and standard deviation are shown for three experiments.

Schwann cells were grown for 21 days and stained with anti S-100 (purple) and Hoechst (blue)

Reference: M. Bechler, L. Byrne, C. Ffrench-Constant, “CNS Myelin Sheaths are an instrinsic property of Oligodendrocytes”. Current Biology 25, 1-6 September 21, 2015

Dr Marie Bechler, a senior researcher in the ffrench-Constant laboratory at the MRC Centre for Regenerative Medicine, said “The aligned Mimetix scaffold fibres have been an invaluable tool, allowing us to answer fundamental questions regarding how oligodendrocytes form central nervous system (CNS) myelin sheaths. The suppliers of the Mimetix fibres worked with us to create customised three-dimensional fibres, facilitating the development of an oligodendrocyte culture assay. The culture system we developed permits the examination of myelin sheath formation in the absence of neurons. The aligned microfibres used in our research have enabled us to examine both the physical and molecular signals sufficient to drive CNS myelin sheath formation, which could not be assessed in other culture models. This has opened new opportunities to examine the role of physical cues, heterogeneity due to oligodendrocyte origin, and the sufficiency of molecules to control the number and size of myelin sheaths formed by oligodendrocytes. Our findings and future work illuminate how myelin sheaths are formed during brain and spinal cord development as well as what signals enhance myelin sheath formation. This research is of particular importance for developing future therapies for diseases of myelin loss, such as multiple sclerosis and leukodystrophies”.

Dr Bechler