Pre-activation status impacts regenerative potential of oligodendrocyte progenitors in an LPS-exposed animal model

Optimal neural activity in the central nervous system relies on the myelin sheath formed by oligodendrocytes. During demyelination, changes in the microenvironment can activate oligodendrocyte precursor cells (OPCs) and induce them to generate new oligodendrocytes. However, different demyelination models employ distinct pathways, targeting different cells and cytokines; these, in turn, have varying effects on OPCs. Therefore, it is reasonable to assume that OPCs derived from different pathologic environment may exhibit functional differences. This study aims to investigate the influence of the pre-activation of OPCs, isolated from lipopolysaccharide (LPS)-induced and cuprizone (CPZ)-induced demyelination models, on their regenerative capacity.

OPCs were isolated from mice subjected to LPS or CPZ-induced neurodegeneration. Characterization and activation assessment included immunostaining for PDGFRα, OLIG2, and ELISA analysis for IL-1, and SOX10 expression assessment. Then OPCs were intravenously transplanted into LPS-exposed mice. The migration patterns of transplanted OPCs were tracked using DiI labeling. After 7 days, spinal cords were assessed for myelin content and integrity (Luxol fast blue, Transmission electron microscopy, MBP and MOG analysis) and extracellular matrix changes (chondroitin sulfate proteoglycan-CSPG levels).

Transplantation of LPS-OPCs significantly enhanced their migration to the demyelinated spinal cord, correlating with increased myelin content and integrity and a reduction in CSPG levels compared to the CPZ-pre-activated OPCs and control groups.

Our findings suggest that the pre-activation environment, determined by the source model, differentially affects the regenerative potential of transplanted OPCs.