Olfactory ensheathing cells (OECs) are a unique type of macroglia required for normal olfactory axonal regeneration throughout the lifetime of an individual. Recent evidence in the literature suggests that OECs transplanted into injured spinal cords may facilitate axonal regeneration. In this study, we evaluated the neurotrophic properties of OECs using a homogeneous clonal cell line (nOEC), which does not contain contaminating cell types found in all primary OEC cultures. The results indicate that nOECs express mRNA for NGF, BDNF, NT‐4/5, and neuregulins, but not for NT‐3 or CNTF. In addition, nOECs secrete NGF, BDNF, and neuregulin, but retain NT‐4/5 intracellularly. Finally, prelabeled nOECs derived from rat survived transplantation into a dorsal hemisected region of the hamster spinal cord and migrated only in the injured, dorsal portion of the spinal cord. This migratory pattern suggests that the nOECs are viable in vivo and respond to signals originating from the injured neuronal cells and their processes. GLIA 33:225–229, 2001. © 2001 Wiley‐Liss, Inc.

Olfactory ensheathing cells (OECs) are a unique type of macroglia required for normal olfactory axonal regeneration throughout the lifetime of an individual. Recent evidence in the literature suggests that OECs transplanted into injured spinal cords may facilitate axonal regeneration. In this study, we evaluated the neurotrophic properties of OECs using a homogeneous clonal cell line (nOEC), which does not contain contaminating cell types found in all primary OEC cultures. The results indicate that nOECs express mRNA for NGF, BDNF, NT-4/5, and neuregulins, but not for NT-3 or CNTF. In addition, nOECs secrete NGF, BDNF, and neuregulin, but retain NT-4/5 intracellularly. Finally, prelabeled nOECs derived from rat survived transplantation into a dorsal hemisected region of the hamster spinal cord and migrated only in the injured, dorsal portion of the spinal cord. This migratory pattern suggests that the nOECs are viable in vivo and respond to signals originating from the injured neuronal cells and their processes.

Neuregulins (NRGs) are growth factors present in neurons and glial cells of the central and peripheral nervous systems and play a role in the survival, proliferation, and differentiation of these cells. We now report the localization of the two major isoforms of NRG (alpha and beta) and their receptors (erbB) in cultured Schwann cells and oligodendrocytes isolated from neonatal rat pups. Immunocytochemistry and Western blots for NRG and erbB receptors in defined subcellular fractions were utilized to assess cellular localization. Less differentiated oligodendrocytes contain both NRG isoforms in the cell bodies but not the processes, while only NRG-1beta was found in the nucleus. In contrast, more differentiated oligodendrocytes contained neither isoform in the nucleus while both isoforms were colocalized in the cytoplasm and cell processes. In Schwann cells, both NRG-1beta and NRG-1alpha were colocalized in the cytoplasm and processes. The Schwann cell nucleus had weak immunoreactivity for both NRG-1 isoforms, although NRG-1beta was predominant. ErbB2 and erbB3 receptors, which transduce the NRG-1 signal in Schwann cells, were found throughout the cytoplasm and in the processes and were also localized in the cell nucleus. The nuclear localization of NRG-1 isoforms and/or erbB receptors in both cell types was confirmed by Western blotting of nuclear and cytoplasmic extracts. Stimulation of Schwann cells with mitotic agents increased NRG-1beta expression in the nucleus and dramatically suppressed NRG-1alpha expression throughout the cell. The functional implications of this differential localization in myelinating cells are discussed.

We have previously reported that neonatal rat oligodendrocytes (OLGs) express and secrete neuregulins (NRGs) (Raabe et al., 1997). This laboratory has also shown that NRGs stimulate the differentiation of neonatal rat OLGs and that these cells express the erbB receptors for NRGs (Raabe et al., 1997). In this study, we have characterized NRG expression in adult human OLG cultures isolated from the temporal lobe resection of intractable epilepsy patients. Using immunocytochemistry and Western blotting, we find that adult human OLGs contain both the α and β isoforms of NRGs. In addition, Western blots show that the adult human OLGs secrete both isoforms as N‐glycosylated molecules. These cells also express all four erbB receptor subtypes, and possibly an activated erbB receptor. The observation that these cells synthesize and secrete their own NRGs, and possibly express a tyrosine‐phosphorylated erbB receptor, is consistent with autocrine and/or paracrine signaling. Amplification of this signaling may provide a useful mechanism to stimulate differentiation of adult human OLGs in demyelinating disease. GLIA 32:304–312, 2000. © 2000 Wiley‐Liss, Inc.