The role of microenvironment in the regenerative potential of neural stem cells after spinal cord injury

Abstract

Spinal cord injury (SCI) results in permanent loss of myelin forming oligodendrocytes that significantly contribute to white matter degeneration. Despite the existence of multipotent neural precursor cells (NPCs) inside the spinal cord, replacement of oligodendrocytes is severely limited after SCI. Interestingly, NPCs mainly contribute to oligodendrocyte turnover in the normal spinal cord; however, in SCI activated NPCs predominantly differentiate into astrocytes and contribute to scar formation. To date, we have only a poor understanding of the extracellular events that modulate NPCs in their post‐SCI niche. After SCI, local microenvironment undergoes profound modifications that limit the regenerative capacities of NPCs. Optimizing the SCI microenvironment is therefore critical not only to promote NPCs cell replacement, but also to attenuate the otherwise non‐constructive effects of NPCs activation after SCI. We have recently identified several mechanisms that influence the behaviour of NPCs after SCI. Our data suggest a role for the matrix molecules chondroitin sulfate proteoglycans (CSPGs) in limiting the activation and differentiation of NPCs after SCI. We also show that the inadequate oligodendrocyte cell replacement in SCI may be attributed to the impaired expression of neureglulin‐1/ErbB signalling in the spinal cord. This talk will discuss our recent research findings in these areas