Meningeal cells enhance limited CNS remyelination by transplanted olfactory ensheathing cells

Olfactory ensheathing cells (OECs) are candidate cells for transplant-mediated repair of persistent demyelination in diseases such as multiple sclerosis. If this approach is to make the transition from laboratory to clinic, an important issue is the most suitable composition of the OEC transplant. Isolation of OECs involves concurrent isolation of other cell types, and specific selection techniques are required to produce purified OECs. In this study we address whether the purity of the OEC transplant affects their ability to remyelinate. Surprisingly, we find that a purified preparation of OECs, selected on the basis of low-affinity nerve growth factor receptor (p75) expression, results in less extensive remyelination than an unpurified preparation following transplantation into areas of persistent demyelination in rodent CNS in the X-irradiation/ethidium bromide (X-EB) model. A distinctive feature of the unpurified preparation both in vitro and following transplantation is the presence of meningeal cells. When meningeal cells are added to purified OECs there is a significant improvement in the extent of remyelination compared with the purified OECs, although if the cells are present in too great an abundance this beneficial effect is lost. These results highlight the important concept that the regenerative properties of OECs are profoundly influenced by the cells with which they are transplanted.