title: Mesenchymal Stem Cell Treatment of Intervertebral Disc Lesion Prevents Fatty Infiltration and Fibrosis of the Multifidus Muscle, but not Cytokine and Muscle Fiber Changes.
abstract: METHODS
  Longitudinal case-control animal model.
  
  
  OBJECTIVE
  To investigate effects of mesenchymal stem cell (MSC) treatment on multifidus muscle remodeling after intervertebral disc (IVD) lesion.
  
  
  BACKGROUND
  Lesion and degeneration of IVDs cause structural remodeling of the multifidus muscle. Proinflammatory cytokines are thought to contribute. MSC treatment restores IVD health after lesion but its effects on surrounding tissues remains unknown. Using an animal model of IVD degeneration, we assessed the effects of MSC treatment of IVDs on the structural remodeling and cytokine expression within the multifidus muscle.
  
  
  METHODS
  An anterolateral lesion was performed on the L1-2, L3-4, and L5-6 IVDs in sheep. At either 4 (early treatment) or 12 (late treatment) weeks after IVD lesion, MSCs were injected into the lesioned IVD. Multifidus muscle was harvested from L2 (gene expression analysis) and L4 (histological analysis) at 3 or 6 months after IVD lesion and naïve controls for histological analysis of muscle, adipose, and connective tissue cross-sectional areas, and immunohistochemistry to study muscle fiber types. Real-time polymerase chain reactions quantified expression of tumor necrosis factor, interleukin-1β, and transforming growth factor-β1.
  
  
  RESULTS
  MSC treatment of IVD lesion prevented the increased adipose and connective tissue cross-sectional area expected after IVD lesion. MSC treatment did not prevent slow-to-fast muscle fiber type transformation. Gene expression of proinflammatory cytokines within the muscle was altered by the MSC treatment of IVD. Increased interleukin-1β expression was prevented in the early treatment group and tumor necrosis factor and transforming growth factor-β1 expression was upregulated at 6 months.
  
  
  CONCLUSIONS
  Results show that although MSC treatment prevents fatty infiltration and fibrosis of the multifidus muscle after IVD lesion, it cannot prevent a muscle inflammatory response and muscle fiber transformation. These findings highlight the potential role of MSC therapy after IVD injury, but reveals that other interventions may also be necessary to optimize recovery of muscle.
  
  
  METHODS
  4.
authors.affiliation: Centre of Clinical Research Excellence in Spinal Pain, Injury & Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: James
authors.affiliation: Centre of Clinical Research Excellence in Spinal Pain, Injury & Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Blomster
authors.affiliation: Centre of Clinical Research Excellence in Spinal Pain, Injury & Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia.
authors.forename: Leanne
authors.initials: L
authors.lastname: Hall
authors.affiliation: Centre of Clinical Research Excellence in Spinal Pain, Injury & Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia.|Nuffield Department of Clinical Neurosciences, Oxford University, United Kingdom.
authors.forename: Annina B
authors.initials: AB
authors.lastname: Schmid
authors.affiliation: Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, The Royal North Shore Hospital, University of Sydney, St Leonards, NSW.
authors.forename: Cindy C
authors.initials: CC
authors.lastname: Shu
authors.affiliation: Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, The Royal North Shore Hospital, University of Sydney, St Leonards, NSW.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Little
authors.affiliation: Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, The Royal North Shore Hospital, University of Sydney, St Leonards, NSW.|Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Melrose
authors.affiliation: Centre of Clinical Research Excellence in Spinal Pain, Injury & Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Hodges
mesh_terms: D000818:Animals; D003238:Connective Tissue / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007403:Intervertebral Disc / Q000601:surgery; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D064170:Paraspinal Muscles / Q000166:cytology*; D012756:Sheep
chemical_list: D016207:Cytokines