Identification of nonepithelial multipotent cells in the embryonic olfactory mucosa.

Olfactory mucosal (OM) tissue, a potential source of stem cells, is currently being assessed in the clinic as a candidate tissue for transplant-mediated repair of spinal cord injury. We examined the ability of embryonic rat OM tissue to generate stem cells using culture conditions known to promote neural stem cell proliferation. Primary spheres formed that proliferated and exhibited two main morphologies: (a) CNS neurosphere-like (OM-I) and (b) small, tight spheroid-like (OM-II). The OM-I spheres expressed the neural stem cell marker nestin but also markers of peripheral glia, neurons, and connective tissue. Further studies demonstrated the presence of multipotential mesenchymal-like stem cells within OM-I spheres that differentiated into bone, adipose, and smooth muscle cells. In contrast, the OM-II spheres contained mainly cytokeratin-expressing cells. Immunolabeling of rat olfactory tissue with Stro-1, CD90, and CD105 showed the presence of multipotent mesenchymal cells in the lamina propria, whereas cytokeratin was expressed by the epithelial cells of the olfactory epithelium. In addition, a comparable pattern of immunoreactivity was detected in human tissue using Stro-1 and cytokeratin, suggesting the presence of similar cells in this tissue. The identification of a nonepithelial multipotent cell in the OM may explain the varied reports on olfactory stem cell differentiation capacity in vitro and in vivo and illustrates the cellular complexity of this tissue as a potential source of stem cells for transplantation and translation to the clinic.