title: Injection of human umbilical tissue-derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo.
abstract: BACKGROUND
  Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery.
  
  
  OBJECTIVE
  To determine whether injecting human umbilical tissue-derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD.
  
  
  METHODS
  Prospective, randomized, blinded placebo-controlled in vivo study.
  
  
  METHODS
  Skeletally mature New Zealand white rabbits.
  
  
  METHODS
  Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology.
  
  
  METHODS
  Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2-L3, L3-L4, and L4-L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4-L5 were analyzed histologically. The L3-L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated.
  
  
  RESULTS
  Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically significant difference from the punctured values. There were no statistically significant MRI differences among the three treatment groups. The treated groups also demonstrated viscoelastic properties that were distinct from the control and punctured values, with the cell curve more similar to the punctured curve and the carrier curve and carrier+cells curve more similar to the control curve (although no creep differences achieved statistical significance). There was some histological evidence of improved cellularity and disc architecture in the treated discs compared with the punctured discs.
  
  
  CONCLUSIONS
  Treatment of degenerating rabbit intervertebral discs with hUTC in a hydrogel carrier solution might help restore the MRI, histological, and biomechanical properties toward those of nondegenerated controls. Treatment with cells in saline or a hydrogel carrier devoid of cells also might help restore some imaging, architectural, and physical properties to the degenerating disc. These data support the potential use of therapeutic cells in the treatment of disc degeneration.
authors: Department of Orthopedics, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213, USA. leckiesk@upmc.edu
authors: Steven K
authors: SK
authors: Leckie
authors: Gwendolyn A
authors: GA
authors: Sowa
authors: Bernard P
authors: BP
authors: Bechara
authors: Robert A
authors: RA
authors: Hartman
authors: Joao Paulo
authors: JP
authors: Coelho
authors: William T
authors: WT
authors: Witt
authors: Qing D
authors: QD
authors: Dong
authors: Brent W
authors: BW
authors: Bowman
authors: Kevin M
authors: KM
authors: Bell
authors: Nam V
authors: NV
authors: Vo
authors: Brian C
authors: BC
authors: Kramer
authors: James D
authors: JD
authors: Kang
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D011446:Prospective Studies; D011817:Rabbits; D014470:Umbilical Cord / Q000166:cytology*
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