title: Tissue-engineered allograft intervertebral disc transplantation for the treatment of degenerative disc disease: experimental study in a beagle model.
abstract: OBJECTIVE
  To investigate whether the intervention of nucleus pulposus (NP) cells or human telomerase reverse transcriptase (hTERT) gene-transfected NP cells can prevent the degeneration process after allograft total disc transplantation.
  
  
  METHODS
  Eighteen canine lumbar intervertebral discs were obtained from five canines and cryopreserved in liquid nitrogen. Canine nucleus pulposus cells were isolated and transduced with recombinant adeno-associated virus (rAAV)-hTERT. The cells were injected into the discs to construct a tissue-engineered allograft disc (group A). NP cells and DMEM/F12 were used for positive control (group B) and blank control (group C). 18 beagle dogs received the three groups of allograft intervertebral disc (IVD) composites implantation, respectively. Radiographic examinations were performed at 4, 8, and 12 weeks postimplantation. At 12 weeks after operation, all dogs were sacrificed and the lumbar spines were harvested for the biomechanical analysis, and then the allografts underwent histological analysis, ectogenic NP cell tracing, and hTERT mRNA analysis.
  
  
  RESULTS
  Bony fusion between the intervertebral disc allograft and the adjacent host intervertebral body were observed in all animals. The disc height and T2 signal intensity preservation in group A and B was better than group C. Magnetic resonance images (MRI) showed typical degenerative changes in group C. In group A, the normalized grayscale of the transplanted disc on MRI was significant higher compared with the controls at 12 weeks. A biomechanical test showed a poor stability preservation in group C compared to group A and B. PKH-26-positive cells were identified within the allograft discs in group A at 12 weeks, providing evidence of cell survival. Histological analysis showed the NP cell morphology, cell number, and distribution of the allograft discs was better preserved in group A and B compared to group C at a 12-week follow-up.
  
  
  CONCLUSIONS
  The present study demonstrated that NP cells or hTERT-loaded NP cells intervention could effectively resist the degeneration of the allogenic transplanted intervertebral discs in a beagle model. The hTERT-loaded NP cells had a better antidegeneration effect on the transplanted disc than NP cells. This modified disc regeneration technique through NP cell injection or manipulation may have the potential to ensure the long-term function preservation of allograft disc transplantation.
authors: Department of of Orthopedics and Traumatology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Hongkui
authors: H
authors: Xin
authors: Chao
authors: C
authors: Zhang
authors: Deli
authors: D
authors: Wang
authors: Zhiyuan
authors: Z
authors: Shi
authors: Tao
authors: T
authors: Gu
authors: Chaofeng
authors: C
authors: Wang
authors: Jianhong
authors: J
authors: Wu
authors: Yan
authors: Y
authors: Zhang
authors: Qing
authors: Q
authors: He
authors: Dike
authors: D
authors: Ruan
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D004285:Dogs; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology* / Q000637:transplantation*; D055959:Intervertebral Disc Degeneration / Q000473:pathology* / Q000601:surgery*; D023822:Tissue Engineering / Q000379:methods*; D016896:Treatment Outcome