Olfactory ensheathing cells (OECs) are specialized, non-myelinating glia that play an integral role in maintaining axonal connections between olfactory sensory neurons in the periphery and glomeruli in the olfactory bulb. Olfactory sensory neurons are replaced continually throughout adulthood, suggesting that OECs retain an ability to interact with or promote axons growth from the periphery to the bulb. In vitro cultures of OECs have been difficult to establish, due in part to their generally low turnover, limiting the ability to easily perform mechanistic studies on OEC function. Objectives and Experimental Methods: Here, we derived an organoid culture model from a patient with a well-differentiated, low grade OEC tumor that was invading along the olfactory nerve. Results: Immunohistochemistry revealed that the tumor was S100B (+) and CD57 (-), confirming the diagnosis. Cells from the low-grade OEC tumor grew well in culture for >10 passages and maintained an OEC-like state with expression of key OEC marker proteins, including S100B and SOX10. The architecture of organoid cultures recapitulates the histologic organization of the original tumor specimen, suggesting that 3D cellular interactions are retained in vitro. Mass spectrometry proteomic assay of organoid-conditioned medium provided a measure of the OEC secretome, revealing the presence of important juxtacrine signaling factors, including semaphorins, while paracrine mediators were largely absent. Conclusions: the OEC culture model will be useful for co-culture assays with olfactory neurons and progenitors and provides a means for identifying mechanisms of OEC function.
Funding: NIH DC016859 (to BJG) and F30DC021348 (to JBF).