The link between olfactory ensheathing cell survival and spinal cord injury repair: a commentary on common limitations of contemporary research.

Olfactory ensheathing cells (OECs) are crucial players in the continuous regeneration of the olfactory nervous system that occurs through out life and are thought to have unique growth-promoting properties. For this reason, OEC transplantation has been thoroughly explored for the potential to promote neural repair after both central and peripheral nervous system injuries. Numerous studies have shown that OEC transplantation is safe and can promote recovery after spinal cord injury (SCI), both in animal models and in human clinical trials. To date, a variety of injury types and time-points after injury, as well as different delivery methods, have been tested. Outcomes have been encouraging (in rodent models including, for example, restoration of locomotion, breathing and climbing ability along with induction of axonal sprouting and some axonal regeneration) but highly variable (Barnett and Riddell, 2007; Gomez et al., 2018). In their natural environment of the primary olfactory nervous system (the olfactory nerve and outer layer of the olfactory bulb), OECs provide structural support for olfactory axons and secrete a range of growth and guidance factors as well as basement membrane components. OECs also phagocytose debris arising from degenerating axons (Ekberg and St John, 2014). In the injured spinal cord, OECs (in addition to these functions) also exhibit a unique capacity for migration into scar tissue and for integration with astrocytes (Barnett and Riddell, 2007; Gomez et al., 2018). For these neural repair effects to occur, it is essential that the transplanted cells survive over time. The key factor for success is thus that the OECs must not only arrive at the right place within the injury site, but must also over time integrate and interact with the injured tissue.