Olfactory sphere cells are a cell source for γ-aminobutyric acid-producing neurons.

Abstract

Olfactory sphere cells (OSCs) are stem cells generated by culturing olfactory mucosa. Adult rat OSCs express oligodendrocyte progenitor cell (OPC) markers and differentiate into mature oligodendrocytes. Although OSCs also express nestin, a marker of neural stem cells (NSCs), it remains unclear whether adult rat OSCs are multipotent and capable of giving rise to neurons as well as oligodendrocytes. Valproic acid (VPA) is a histone deacetylase inhibitor that has the contradictory capacity to induce both differentiation of NSCs and dedifferentiation of OPCs. This study investigates a potential role for VPA in inducing either differentiation or dedifferentiation of adult rat OSCs. Treatment of OSCs with VPA induced hyperacetylation of histones and decreased cell proliferation in the absence of changes in the number of nestin-positive cells. Furthermore, VPA promoted the genesis of γ-aminobutyric acid (GABA)-producing neurons identified by expression of Tuj1/GAD67/GABA while repressing oligodendrocyte production. These findings suggest that OSCs treated with VPA did not exhibit stem cell properties indicative of dedifferentiation but rather switched to a neuronal identity during their terminal differentiation. OSCs were then transplanted into the hippocampus of rats with kainic acid-induced temporal lobe epilepsy and were systemically given VPA. Although grafted OSCs expressed Tuj1 and GAD67, these cells did not sufficiently inhibit epileptic activity. These results suggest that OSCs are a transplantable cell source for GABA-producing neurons that can be modulated by VPA. However, further investigation is required to develop them for clinical applications.