With over 700,000 affected patients in the EU, Multiple Sclerosis (MS) represents the most frequently occurring demyelinating disease of the central nervous system (CNS). Remyelination can be observed in MS plaques. But as disease progresses this regenerative capacity of oligodendrocyte progenitor cells (OPCs) stops.
There is growing evidence that matrix rigidity plays a key role in the process of OPC differentiation by unbalancing the intra/extracellular forces. To understand when/how the changes in a brain lesion environment occur and how these condition the progress of disease we propose the use of a nanomaterial-based “tool box” by constructing a three-dimensional (3D) tissue engineered model of the scar to mimic the pathological environment at different stages of the disease.
This innovative approach will allow: (1) a systematic evaluation of the impact of the mechanical properties on the progress of the disease, and (2) the high-throughput screen for OPC differentiation inhibitors/enhancers. Ultimately, contributing to the development of new therapeutic approaches to treat MS.
|Title||From the mechanobiology of the glial to the management of multiple sclerosis|
|Leading Institution||Instituto Nacional de Engenharia Biomédica (INEB Porto)|
|Participating Institutions||The University of Austin at Texas (UT Austin)
Instituto Politécnico de Leiria (IPLeiria)
|Begin date||1st November, 2018|
|End date||31st October, 2020 (extended)|
|Key Words||Nanomedicine, Molecularly Designed Hydrogels, Mechanobiology, Bioprinting|
"The progression of MS is characterised by a cessation of the regenerative capacity of oligodendrocyte progenitor cells (OPCs). There is growing evidence that the matrix rigidity plays a key role in the process of OPC differentiation and oligodendrocyte myelination by unbalancing the intra/extracellular forces. Recent studies have established the effect of biophysical properties of the extracellular matrix on the processes, pointing to the importance of ECM stiffness and topography, strain forces and spatial constrains. Based on current knowledge, our working hypothesis is that by tuning mechanosensing processes one can promote demyelination. To understand when/how the changes in the brain lesion biophysical environment occur and how this condition the progress of the disease, we propose the use of a nanonmaterial-based "tool box" by constructing a three-dimensional (3D) tissue engineered model of a CNS scar."