Heterogeneity of local tissue microenvironment influences differentiation of oligodendroglial progenitors

摘要

Glial NG2-positive precursors are considered as suitable candidates for the cell-based therapies for disorders characterised by depletion of functional oligodendrocytes and ongoing hypo/demyelination. They are known to be among the first cells to react to CNS dysfunction. Their fate could be however considerably affected by the heterogeneity of the local tissue microenvironment. To address this issue, a comparison of mRNA expression of the crucial trophic factors was carried out in organotypic slices from the hippocampus (as a well-recognised neurogenic area) and from the spinal cord (where gliogenic signals are assumed to predominate). The molecular analysis revealed substantial differences in the mRNA levels of main factors governing cell biology. Additionally, the ability of these two microenvironments to promote the astrocytic differentiation of oligodendroglial progenitors was assessed as well. While the GFAP+ cells constituted the very minor population in control experiments, their amount increased significantly during culturing in the medium continuously conditioned by either hippocampal or the spinal cord slices. The observed susceptibility to the influence of the local extracellular signals might efficiently contribute to the reported glial scar formation. It presumably could also modify the fate of the endogenous or transplanted precursors, what should be taken into consideration in cell-based therapies.