title: Activated autologous macrophage implantation in a large-animal model of spinal cord injury.
abstract: OBJECTIVE
  Axonal regeneration may be hindered following spinal cord injury (SCI) by a limited immune response and insufficient macrophage recruitment. This limitation has been partially surmounted in small-mammal models of SCI by implanting activated autologous macrophages (AAMs). The authors sought to replicate these results in a canine model of partial SCI.
  
  
  METHODS
  Six dogs underwent left T-13 spinal cord hemisection. The AAMs were implanted at both ends of the lesion in 4 dogs, and 2 other dogs received sham implantations of cell media. Cortical motor evoked potentials (MEPs) were used to assess electrophysiological recovery. Functional motor recovery was assessed with a modified Tarlov Scale. After 9 months, animals were injected with wheat germ agglutinin-horseradish peroxidase at L-2 and killed for histological assessment.
  
  
  RESULTS
  Three of the 4 dogs that received AAM implants and 1 of the 2 negative control dogs showed clear recovery of MEP response. Behavioral assessment showed no difference in motor function between the AAM-treated and control groups. Histological investigation with an axonal retrograde tracer showed neither local fiber crossing nor significant uptake in the contralateral red nucleus in both implanted and negative control groups.
  
  
  CONCLUSIONS
  In a large-animal model of partial SCI treated with implanted AAMs, the authors saw no morphological or histological evidence of axonal regeneration. Although they observed partial electrophysiological and functional motor recovery in all dogs, this recovery was not enhanced in animals treated with implanted AAMs. Furthermore, there was no morphological or histological evidence of axonal regeneration in animals with implants that accounted for the observed recovery. The explanation for this finding is probably multifactorial, but the authors believe that the AAM implantation does not produce axonal regeneration, and therefore is a technology that requires further investigation before it can be clinically relied on to ameliorate SCI.
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Rachid
authors.initials: R
authors.lastname: Assina
authors.forename: Tejas
authors.initials: T
authors.lastname: Sankar
authors.forename: Nicholas
authors.initials: N
authors.lastname: Theodore
authors.forename: Sam P
authors.initials: SP
authors.lastname: Javedan
authors.forename: Alan R
authors.initials: AR
authors.lastname: Gibson
authors.forename: Kris M
authors.initials: KM
authors.lastname: Horn
authors.forename: Michael
authors.initials: M
authors.lastname: Berens
authors.forename: Volker K H
authors.initials: VK
authors.lastname: Sonntag
authors.forename: Mark C
authors.initials: MC
authors.lastname: Preul
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D007167:Immunotherapy / Q000379:methods*; D007796:Laminectomy / Q000379:methods; D008264:Macrophages / Q000276:immunology*; D009416:Nerve Regeneration; D020127:Recovery of Function; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery*; D013997:Time Factors; D014182:Transplantation, Autologous / Q000379:methods; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
chemical_list: D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate