STRESS - TOWARDS THE STUDY OF THE IMPACT OF ENVIRONMENTAL MECHANOSTIMULUS ON OLIGODENDROCYTE PRECURSOR DIFFERENTIATION AND MYELINATION
Abstract
Myelin, the lipid rich substance that insulate neurons, is essential for the fast saltatory conduction of electrical impulse in neurons. The loss of myelin sheath due to an insult and/or disease leads to central nervous system (CNS) dysfunction. A population of precursor cells called oligodendrocyte precursor cells (OPCs), which are present throughout the adult CNS, differentiate and is responsible for the process of remyelination. Although this process can efficiently culminate in regeneration, it is often insufficient and inadequate. The formation of a glial scar containing reactive astrocytes producing high amounts of extracellular matrix (ECM) proteins during demyelination contributes to mechanical alterations in the lesioned tissue. Growing evidences suggest that the ECM mechanical environment is a key player during OPC differentiation. Nevertheless, the study of the mechanobiology of these important glial cells is clearly in its infancy and many relevant questions remain. Do stiffness alterations caused by external conditions or as consequence of trauma or disease, have a significant impact on the course of OPC remyelination? Here, a novel fully tissue-engineered 3D model will be developed and used to unveil the role of ECM stiffness on OPC differentiation. For the first time, an innovative approach to dynamically model alterations in the ECM that surrounds OPC and astrocytes, will be implemented by tuning the matrix mechanical properties in a phototunable hydrogel. The proposed model will allow us to assess the impact of matrix mechanical properties alterations in healthy tissue and in demyelinating conditions and dissect related mechanotransduction pathways, hence contributing towards the understanding of the mechanisms that underlie (re)myelination failure. Ultimately, our working hypothesis is that by tuning glial scarmechanosensing mediated pathways one can promote (re)myelination.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 12, 2021
- Source ID
- FA95502010417
Entities
People
- Ana Paula Pêgo
Organizations
- Air Force Office of Scientific Research
- United States Air Force