title: Cervical interbody fusion is enhanced by allogeneic mesenchymal precursor cells in an ovine model.
abstract: METHODS
  An experimental study using a sheep cervical spine interbody fusion model.
  
  
  OBJECTIVE
  To compare allogeneic mesenchymal precursor cells combined with hydroxyapatite and tricalcium phosphate (HA/TCP) with HA/TCP alone or iliac crest autograft (AG) for cervical interbody fusion.
  
  
  BACKGROUND
  We investigated the effect of mesenchymal precursor cells on cervical fusion because of the shortcomings of using iliac crest (donor site morbidity), bone substitute (poor osteoinductive properties), and bone morphogenic proteins (serious complications).
  
  
  METHODS
  Thirty ewes were divided randomly into four groups of six having C3-C4 anterior cervical discectomy and fusion using a Fidji cage packed with, AG, HA/TCP, HA/TCP containing 5 million MPCs, and HA/TCP containing 10 million MPCs. MPCs were derived from a single batch of immuno-selected and culture-expanded MPCs isolated from bone marrow of out-bred sheep. The fifth group were nonoperated controls. Safety, fusion parameters, and biomechanics were assessed.
  
  
  RESULTS
  No cell-related adverse events were observed. No significant differences were found between the five or 10 million MPC groups. Evaluation of fusion by CT scan at 3 months showed that 9 of 12 (75%) MPC-treated animals had continuous bony bridging compared with only 1 of 6 AG and 2 of 6 HA/TCP (P = 0.019 and P = 0.044, respectively). By quantitative CT, density of new bone in MPC-treated animals was 121% higher than in HA/TCP (P = 0.017) and 128% higher than in AG (P < 0.0001). Functional radiology at 3 months revealed that MPC-treated animals had significantly reduced macromotion at C3/4 compared with AG and HA/TCP groups combined (P = 0.007).
  
  
  CONCLUSIONS
  Implantation of allogeneic MPCs when combined with HA/TCP and an interbody spacer facilitates new bone formation after discectomy without any cell-related complications. The earlier and dense new bone formation observed with MPCs relative to autograft and HA/TCP alone suggest that this approach may offer therapeutic benefit.
authors.affiliation: Monash Immunology and Stem Cell Laboratories, Department of Surgery, Monash University, Victoria, Australia. tony.goldschlager@med.monash.edu.au
authors.forename: Tony
authors.initials: T
authors.lastname: Goldschlager
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Rosenfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Ghosh
authors.forename: Silviu
authors.initials: S
authors.lastname: Itescu
authors.forename: Carl
authors.initials: C
authors.lastname: Blecher
authors.forename: Catriona
authors.initials: C
authors.lastname: McLean
authors.forename: Graham
authors.initials: G
authors.lastname: Jenkin
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000494:pharmacology; D002574:Cervical Vertebrae / Q000601:surgery*; D017586:Diskectomy; D017886:Durapatite / Q000494:pharmacology; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects; D011897:Random Allocation; D012756:Sheep; D013123:Spinal Fusion / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D017886:Durapatite; C018392:tricalcium phosphate