10.2217/14796708.1.4.453 © 2006 Future Medicine Ltd ISSN 1479-6708 Future Neurol. (2006) 1(4), 453–463 453 REVIEW Olfactory ensheathing glia and spinal cord injury: basic mechanisms to transplantation Alan R Harvey † & Giles W Plant † Author for correspondence The University of Western Australia, Red’s Spinal Cord Research Laboratory, School of Anatomy and Human Biology, 35 Stirling Highway, Crawley, Perth, WA 6009, Australia Tel.: +61 864 883 294; Fax: +61 864 881 051; arharvey@anhb.uwa.edu.au Keywords: cell death, gene therapy, glia, neurotrauma, olfactory, spinal cord The adult CNS, unlike its counterpart the peripheral nervous system (PNS), has little ability to repair itself after traumatic injury. Therefore, neurotrauma involving the brain or spinal cord has severe and long-lasting functional consequences for injured patients, as well as a massive financial and social impact on the affected families and the community at large. In particular, spinal cord injury (SCI) has provided scientists and clinicians with a challenging problem. In attempts to improve outcomes following SCI, numerous mammalian research models have been developed. Many of these models involve either transection or contusion injuries in rodents and experimental therapies include the transplantation of a range of cell types isolated from either the PNS or CNS. The authors focus on a cell type isolated from the olfactory system; olfactory ensheathing cells (OECs). Some basic tenets of olfactory cell biology, key preclinical results suggesting a role for OECs in stimulating spinal cord repair and the strengths and limitations of this potential therapy are discussed. The current and future status of OEC transplantation in the treatment of human SCI is also considered. Olfactory ensheathing cells (OECs) are special- ized glial cells found in the mammalian olfactory system. T hey are located within the olfactory epithelium/lamina propria and olfactory bulb of the olfactory pathway. OECs surround olfactory sensory axons as the fibers exit the olfactory epi- thelium and they are closely associated with these axons as they extend from the nose to their targets in the brain. OECs share a number of phenotypic properties with peripheral glia (Schwann cells) and central glia, such as astro- cytes. T hese shared properties may help to explain why OECs are able to function effec- tively in both the periphery and CNS. The pri- mary olfactory system is also unusual in that sensory neurons are replaced throughout adult life, a process known as neurogenesis. O ECs are thought to play an important role in this process, as well as in the guidance of newly formed axons to their targets in adult CNS tissue. The func- tional properties of OECs and the integral role they play in the highly plastic primary olfactory system have led many to believe that O ECs are a promising candidate for use in CNS repair, particularly after spinal cord injury (SCI). OECs & spinal cord repair From a therapeutic perspective, a cell transplant should ideally be able to achieve a number of out- comes. These include the capacity to intermingle and integrate nondisruptively with host cells within the transplant environment, the ability to promote axonal sparing and regeneration within the adult CNS and the ability to restore myelin around denuded/regrown axons. O ECs have been reported to fulfil all of these properties in SCI, although controversy remains concerning the reproducibility of some experimental observations and functional outcomes. Source & purification of OECs Different methods have been used to obtain OECs for use in transplantation. OECs have mostly been derived from the olfactory bulb in the brain, taken from embryos (E18–E19) [1,2], postnatal rats (P7) [3] or adult animals [4]. In adults, OECs can also be taken more peripher- ally from the lamina propria [5,6], a more acces- sible region in humans and, therefore, of potential clinical importance [7]. OECs can be used with or without additional steps to purify the cell population. Much of the early work in the OEC field involved the use of embryonic cells fed with a cocktail of ingredients, but not immuno- selected for a particular phenotype [1,2]. With the exception of some preliminary studies by the authors [8], it is understood that embryonic OECs have not yet been purified by immuno- selection prior to their use in transplant exper- iments. On the other hand, OECs isolated from postnatal rats have been purified by immunoselection using the O4 antigen, a pro- tein detected immunohistochemically on the surface of OECs in olfactory tissues [3,9]. These O4-selected OECs have been made into clonal For reprint orders, please contact: reprints@futuremedicine.com