Locally transplanted enteric glia improve functional and structural recovery in a rat model of spinal cord injury

BACKGROUND: We have previously reported that adult enteric glia (EG) facilitate the growth of transected dorsal root axons into the uninjured spinal cord to form functional connections with their targets. OBJECTIVE: The present study investigated the effects of EG on spinal cord function, tissue injury, and axonal regeneration following transplantation into injured rat spinal cords, according to histological and functional outcomes. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at McMaster University, Canada from January 2006 to March 2008. MATERIALS: EG were isolated from rat intestine. METHODS: One week following spinal cord crush, female Wistar rats were injected with an EG suspension (2 mu L, 1 x 10(5)/mu L, n = 10) or with the same volume of fresh culture medium alone (control animals, n = 11). The third group did not receive any injection following laminectomy and served as the sham-operated controls (n = 5). MAIN OUTCOME MEASURES: Behavior was tested prior to transplantation and weekly following transplantation, with nine behavioral examinations in total. Open field, hind limb placement response, foot orientation response, and inclined plane test were utilized. Immediately following the final behavioral examination, spinal cord T-9 to L-1 segments were harvested for immunohistochemical and hematoxylin-eosin staining to determine astroglial scarring, axonal regeneration and spinal cord lesion size. RESULTS: Rats with EG transplantation exhibited significantly better locomotor function with reduced tissue damage, compared with the control rats. Cystic cavities were present 2 months after injury in spinal cords from both control groups. In contrast, rats injected with EG did not present with cystic lesions. In addition, the injury site consisted of cellular material and nerve fibers, and axonal regeneration was apparent, with dense labeling of neurofilament-positive axons within the injury site. Moreover, regenerating axons were intimately associated with transplanted EG. CONCLUSION: These data indicated that EG enhanced functional improvement, which was associated with reduced tissue damage and axonal regeneration following transplantation into injured spinal cords.