Quantification of oligodendrocyte progenitor cells in human and cat optic nerve: Implications for endogenous repair in multiple sclerosis

Abstract

In multiple sclerosis (MS), one strategy to reduce disability is enhancement of endogenous repair by remyelinating oligodendrocytes derived from oligodendrocyte progenitor cells (OP). An important prerequisite is determining the abundance of OP relative to oligodendrocytes in normal human central nervous system (CNS), which, in turn, requires reliable OP identification. To achieve this, cat and human optic nerves (ON) were subjected to varied preparation protocols, and the resultant neuroglial staining profiles correlated to generate an antigenic phenotype for OP applicable to human autopsy specimens. OP, interchangeably called NG2cells due to universal NG2 expression, were shown to comprise a separate class of neuroglial cells, related to oligodendrocytes by expression of the oligodendrocyte lineage transcription factors, Olig1 and Olig2. Despite their morphological complexity, including contact with axons and other neuroglia, NG2cells all appear capable of responding as OP to counter local oligodendrocyte loss. However, quantification revealed that NG2cells comprised less than 5% of the neuroglia and had a ratio to oligodendrocytes of about 1:10, not only in human and cat ON but also in white and gray-matter regions of cat spinal cord. The finding that NG2cells are not abundant, particularly relative to oligodendrocytes, may have implications for efforts to enhance endogenous repair in MS.