Schwann Cell Activity in the Multiple Sclerosis Microenvironment

Schwann cell (SC)-based therapy is currently being debated as an approach to promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). The main limitation of SC transplantation in MS patients is the short-term functional activity of SCs in the CNS environment. The goal of this study was to determine phenotypic, functional, and signaling changes in human SCs treated with CSF samples from MS patients in vitro, and to characterize the molecular mechanisms underlying SC injury response in the model MS microenvironment. We demonstrated that SC proliferation and motility were suppressed, while the expression of both pro-myelinating genes and negative regulators of myelination was up-regulated in cells incubated with CSF from MS patients. This was associated with active phosphorylation of ERK and c-Jun, and inhibition of these signaling pathways prevented SC changes. The overall analysis of detected abnormalities and SC markers indicates that SCs do not exhibit either a 'classic' dedifferentiation-repair-like phenotype or a myelin-forming maturation phenotype when placed in MS-like conditions. They demonstrate an uncommon pattern of cellular signaling reprogramming, associated with decreased motility and potentially decreased myelination. We thus suggest that ERK- and JNK-modulated SCs should be further investigated as a potential cell source for CNS repair in MS.