Morphological plasticity of olfactory ensheathing cells is regulated by cAMP and endothelin-1

Olfactory ensheathing cells (ECs) are a promising tool for the repair of injury in the adult central nervous system. However, important aspects of the cell biology of ECs remain unclear, such as whether ECs exist as a single population or as two subpopulations with Schwann cell-like and astrocyte-like characteristics. The morphologies of these subpopulations are used as defining characteristics, yet ECs are known to be morphologically plastic. To elucidate this apparent inconsistency, we investigated the morphological plasticity of ECs in culture. We defined purified ECs as immunopositive for both p75 neurotrophin receptor and glial fibrillary acidic protein. In MEM (D)-valine modification + 10% dialyzed fetal calf serum, 87%-90% of ECs displayed a flat morphology. In three different serum-free media (N2 medium, neurobasal medium + B27 supplement, and DMEM/F-12 medium + G5 supplement), 78%-84% of ECs displayed process-bearing morphology. Ensheathing cells switched reversibly between these morphologies within a day of the serum conditions being changed. Exposure to 1 nM endothelin-1 in serum-free medium prevented the switch from flat to process-bearing morphology, while 1 mM dibutyryl cAMP accelerated this change. The effects of both agents were completely reversible and similar to that reported for astrocytes. Both flat and process-bearing ECs were immunopositive for brain-derived neurotrophic factor, nerve growth factor, neurotrophin-4, and TrkB but not TrkA. Together, these results suggest that ECs exist as a single morphologically plastic population.