Adult Olfactory Ensheathing Cell Transplantation for Acute Spinal Cord Injury

Abstract

Cellular transplantation strategies have been explored for the treatment of spinal cord injury. In particular, olfactory nerve ensheathing cell (OEC) transplantation has been reported to improve functional outcome following injury. We investigated the effect of OEC transplantation using cells derived from adult animals on the restoration of function following a contusion injury to the spinal cord. The NYU impactor was used to create a moderate to severe spinal cord injury in 17 rats. Hoescht stained cultured OECs derived from adult rats (n = 7) or culture medium alone (n = 10) were injected into the injury site immediately following injury. Histological and functional outcomes were measured using immunohistochemistry and the Basso, Beattie, and Bresnahan (BBB) scale. All animals transplanted with OECs were found to have surviving Hoescht positive cells within the spinal cord when sacrificed 6 weeks following injury. Immunohistochemical staining of the explanted cords revealed that the surviving cells stained positively for nerve growth factor receptor. Functional outcomes were not different between the transplanted and control groups. OECs transplanted immediately following a contusion injury to the spinal cord survive during the first 6 weeks following injury. These cells do not appear to influence functional outcome during the first 6 weeks following injury. Additional studies are required in order to definitively determine the utility of this type of cellular transplantation for spinal cord injury.

Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration

“…The anatomical evidence of regeneration (Franklin et al, 1996;Li et al, 1997;Li et al, 1998;Imaizumi et al, 2000;Nash et al, 2002) and functional improvements (Li et al, 1998;Ramon-Cueto et al, 2000;Lu et al, 2001;Lu et al, 2002;López-Vales et al, 2006) have been noted in a variety of spinal cord repair models, including complete transection, hemisection, tract lesion, contusion and demyelination. However, there are some negative reports of OEC transplantation after spinal cord injury (Resnick et al, 2003;Barnett and Riddell, 2004), and it is still debatable whether transplanted OECs can migrate long distances in the injured CNS. Smale et al reported that no significant cell migration was detected when OECs from fetal rat olfactory bulb were implanted into the damaged adult rat brain (Smale et al, 1996).…”

Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury

“…OECs have been reported to migrate extensively in the injured spinal cord, especially when transplanted rostrocaudally in proximity to a lesion site (Ramon-Cueto and Nieto-Sampedro, 1994;Li et al, 1998;Ramon-Cueto et al, 1998;Imaizumi et al, 2000a;Boruch et al, 2001;Keyvan-Fouladi et al, 2003;Resnick et al, 2003;Sasaki et al, 2004). It has been proposed that OECs might respond to signals or factors from injured neurons and their processes, therefore migrating preferentially toward an injury site (Ramon-Cueto et al, 1998;Boruch et al, 2001).…”

“…Previous studies have not examined other cell types as controls for OECs, and have not examined very early time points after cell injection, likely contributing to the potentially mistaken attribution of unique migratory properties to OECs. Previous studies reported migration of OECs over extensive distances beyond a spinal cord lesion site based in part on the use of Hoechst cell labeling (Ramon-Cueto and Nieto-Sampedro, 1994;Ramon-Cueto et al, 1998Boruch et al, 2001;Resnick et al, 2003;Cao et al, 2004;Chuah et al, 2004). However, subsequent reports indicated that the Hoechst label leaks from transplanted cells, leading to spread of the label rather than the implanted cell, causing an artifactual appearance of cell migration (Iwashita et al, 2000;Ruitenberg et al, 2002;Andrews and Stelzner, 2004).…”

“…Lu et al, 2001J. Lu et al, , 2002Nash et al, 2002;Pascual et al, 2002;Ruitenberg et al, 2002Ruitenberg et al, , 2003Ruitenberg et al, , 2005Takami et al, 2002;Gomez et al, 2003;Keyvan-Fouladi et al, 2003;Plant et al, 2003;Resnick et al, 2003;Verdu et al, 2003;Andrews and Stelzner, 2004;Boyd et al, 2004;Cao et al, 2004;Chuah et al, 2004;Garcia-Alias et al, 2004;Lee et al, 2004;Lopez-Vales et al, 2004Pearse et al, 2004;Polentes et al, 2004;Ramer et al, 2004a,b;Riddell et al, 2004;Sasaki et al, 2004;Barakat et al, 2005;Collazos-Castro et al, 2005;Fouad et al, 2005;Richter et al, 2005;Moreno-Flores et al, 2006). Many of the above studies report that OECs promote axonal regeneration and, in some cases, functional recovery, although controversy exists (Gomez et al, 2003;Ramer et al, 2004b;Riddell et al, 2004;Steward et al, 2006).…”

The Immunohistochemical Characterization of Human Fetal Olfactory Bulb and Olfactory Ensheathing Cells in Culture as a Source for Clinical CNS Restoration

“…More and more literature reviews give us more and more hope that OEC transplantation to be one of the most promising therapeutic strategies (Barnett and Riddell, 2007;Sasaki et al, 2007;Bauchet et al, 2008;Bunge, 2008;Radtke et al, 2008;Richter and Roskams, 2008;Kawaja et al, 2009); OECs have been successfully transplanted in acute (Resnick et al, 2003;Polentes et al, 2004;Collazos-Castro et al, 2005;Lopez-Vales et al, 2006;Andrews and Stelzner, 2007;Sasaki et al, 2007) and chronic (Andrews and Stelzner, 2004;Lopez-Vales et al, 2007) models of rodent spinal cord injury. Data obtained using various injury models support the view that OEC transplants can reduce cavitation, increase axonal sprouting and regeneration, and a moderate degree of functional motoric recovery (Li et al, 1997;Ramon-Cueto et al, 2000;Collazos-Castro et al, 2005;Lopez-Vales et al, 2007;Sasaki et al, 2007).…”