title: Allogeneic Mesenchymal Precursor Cells Promote Healing in Postero-lateral Annular Lesions and Improve Indices of Lumbar Intervertebral Disc Degeneration in an Ovine Model.
abstract: METHODS
  In-vivo ovine model of intervertebral disc degeneration (IVD) to evaluate treatment with stem cells.
  
  
  OBJECTIVE
  To determine if stem cells delivered to the nucleus pulposus (NP) or the annulus fibrosus (AF) of degenerated lumbar IVDs leads to improved indices of disc health.
  
  
  BACKGROUND
  Previous studies assessing the efficacy of stem cell injections into degenerated IVDs have reported positive findings. However, studies have been limited to small animals, targeting solely the NP, with short term follow-up.
  
  
  METHODS
  Mesenchymal precursor cells (MSC) were obtained from the iliac crest of 8-week-old sheep. IVD degeneration was induced by postero-lateral annulotomy at three lumbar levels in eight 2-year-old sheep. Six months later, each degenerated IVD was randomized to one of three treatments: Injection of MSC into (i) previously incised AF (AFI), (ii) NP (NPI), or (iii) no injection (negative control, NC). The adjacent IVD received injection of phosphate buffered saline into NP (positive control, PC). Radiographs and magnetic resonance imaging scans were obtained at baseline, 6, 9, and 12 months. Discs were harvested at 12 months for biochemical and histological analyses.
  
  
  RESULTS
  IVD degeneration was consistently observed postannulotomy, and characterized by reduced disc height index (DHI), disc height (DH), glycosaminoglycan (GAG) content, and increased grade of disc degeneration.Six months after stem cell injection, DHI and DH had recovered in AFI and NPI groups when compared with NC group (P < 0.01). Mean Pfirrmann grade improved from 3.25 to 2.67 (AFI group) and from 2.96 to 2.43 (NPI group). Mean histopathological grade improved for both AFI (P < 0.002) and NPI (P < 0.02) groups. Both AFI and NPI groups demonstrated spontaneous repair of the postero-lateral annular lesion.
  
  
  CONCLUSIONS
  In this large animal model, injection of MSCs into the annulus fibrosus or the nucleus pulposus of degenerated IVD resulted in significant improvements in disc health.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Spinal Surgery, Royal Adelaide Hospital, Adelaide, Australia.|Adelaide Centre for Spinal Research, SA Pathology, Adelaide, Australia.|Centre for Orthopedic and Trauma Research, University of Adelaide, Australia.
authors.forename: Brian J C
authors.initials: BJC
authors.lastname: Freeman
authors.affiliation: Adelaide Centre for Spinal Research, SA Pathology, Adelaide, Australia.|Centre for Orthopedic and Trauma Research, University of Adelaide, Australia.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Kuliwaba
authors.affiliation: Adelaide Centre for Spinal Research, SA Pathology, Adelaide, Australia.|Centre for Orthopedic and Trauma Research, University of Adelaide, Australia.
authors.forename: Claire F
authors.initials: CF
authors.lastname: Jones
authors.affiliation: Raymond Purves Bone and Joint Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Australia.
authors.forename: Cindy C
authors.initials: CC
authors.lastname: Shu
authors.affiliation: College of Health Solutions, Arizona State University, Phoenix, AZ.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Colloca
authors.affiliation: Adelaide Centre for Spinal Research, SA Pathology, Adelaide, Australia.|Centre for Orthopedic and Trauma Research, University of Adelaide, Australia.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Zarrinkalam
authors.affiliation: Adelaide Centre for Spinal Research, SA Pathology, Adelaide, Australia.
authors.forename: Adnan
authors.initials: A
authors.lastname: Mulaibrahimovic
authors.affiliation: School of Medical Sciences, Faculty of Health Science, University of Adelaide, Australia.|South Australian Health and Medical Research Institute, Adelaide, Australia.
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, Australia.|Discipline of Physiology, School of Medical Sciences, University of Adelaide, Australia.
authors.forename: Andrew C W
authors.initials: ACW
authors.lastname: Zannettino
authors.affiliation: Data Management and Analysis Centre, University of Adelaide, Adelaide Royal Adelaide Hospital, North Terrace, Adelaide, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Howell
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000032:analysis; D007403:Intervertebral Disc / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000473:pathology* / Q000628:therapy; D008159:Lumbar Vertebrae / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D012756:Sheep; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D006025:Glycosaminoglycans