Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes

Abstract

Transplanted olfactory ensheathing cells (OECs) are able to remyelinate demyelinated axons and support regrowth of transected axons after transplantation into the adult CNS. Transplanted Schwann cells (SCs) share these repair properties but have limitations imposed on their behavior by the presence of astrocytes (ACs). Because OECs exist alongside astrocytes in the olfactory bulb, we have hypothesized that they have advantages over SCs in transplant‐mediated CNS repair due to an increased ability to integrate and migrate within an astrocytic environment. In this study, we have tested this hypothesis by comparing the interactions between astrocytes and either SCs or OECs, using a range of in vitro assays. We have shown that (1) astrocytes and SCs segregate into defined non‐overlapping domains in co‐culture, whereas astrocytes and OECs freely intermingle; (2) both SCs and OECs will migrate across astrocyte monolayers, but only OECs will migrate into an area containing astrocytes; (3) SCs spend less time in contact with astrocytes than do OECs; and (4) astrocytes undergo hypertrophy when in contact with SCs, but not with OECs. Expression of N‐cadherin has been implicated as a key mediator of the failure of SCs to integrate with astrocytes. However, we found no differences in the intensity of N‐cadherin immunoreactivity between SCs and OECs, suggesting that it is not the adhesion molecule that accounts for the observed differences. In addition, the number of astrocytes expressing chondroitin sulfate proteoglycans (CSPG) is increased when astrocytes are co‐cultured with Schwann cells compared with the number when astrocytes are grown alone or with OECs. Taken together, these data support the hypothesis that OECs will integrate more extensively than Schwann cells in astrocytic environments and are therefore better candidates for transplant‐mediated repair of the damaged CNS. GLIA 32:214–225, 2000. © 2000 Wiley‐Liss, Inc.

Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery

“…In a previous study, we reported that, after severe photochemical cord injury, OECs-transplanted rats showed significantly lower area of cystic cavity and lower expression of proteoglycan and glial fibrillary acidic protein (GFAP) by reactive astrocytes in comparison with nontransplanted animals (Verdú et al, 2001). In vitro studies also demonstrated that OECs modulate GFAP and proteoglycan expression in reactive astrocytes (Lakatos et al, 2000(Lakatos et al, , 2002. These results suggest that OECs create a favorable microenvironment at the lesion site that permits the regeneration of central axons.…”

“…In the present study, we confirm these results at a longer time, 3 months postlesion, when the injury process has reached a steady state. Studies that have used cocultures with astrocytes showed that OECs did not induce overexpression of chondroitin sulfate proteoglycans (CSPGs) in astrocytes, whereas cocultured Schwann cells increased CSPG expression in astrocytes (Lakatos et al, 2000(Lakatos et al, , 2002. In vitro studies demonstrated that proteoglycan inhibits neurite outgrowth, and that a monoclonal antibody against proteoglycan neutralized this inhibitory activity (Bovolenta et al, 1997).…”

Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat

“…OECs from neonatal rats were purified as previously described [20]. Briefly, the olfactory gentamicin (Sigma), and 5% FBS (Autogen Bioclear, Wiltshire, UK) on 13 µg/ml poly-Llysine-(PLL) (Sigma) coated 25cm2 flasks (Sigma).…”

“…OECs secrete a host of growth factors, including vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF), all of which are important for neural, glial and endothelial cell function as demonstrated in a number of experimental studies [14][15][16][17][18][19]. Furthermore, compared to Schwann cells, OECs induce less astrocytic response in in vitro confrontation assays [20] as well as following transplantation into adult CNS white matter [21]. We have previously demonstrated the capacity of OECs to promote tissue remodelling, including axonal sparing and plasticity, neovascularization and remyelination after induced central axotomy [19], while a recent clinical report suggests that OECs combined with Schwann cell transplants can promote functional regeneration of supraspinal connections after spinal cord injury [22].…”

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

“…253 Both types of cells have been genetically modified prior to transplantation to deliver growth factors at the lesion site. 245,254,255 OECs have been reported to integrate more successfully with astrocytes, 256 and to induce less glial scarring 257 than SCs, but may themselves express inhibitory molecules (such as Nogo or proteoglycans, discussed in 'Stimulating axonal growth in the injured spinal cord' above) after transplantation. 258 Few experiments have directly compared SC-and OEC-transplantation in the same injury.…”