Prevention and treatment of intervertebral disc degeneration with bone marrow derived stem (stromal) cells - an <em>in vivo</em> study in sheep — The Association Specialists
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Prevention and treatment of intervertebral disc degeneration with bone marrow derived stem (stromal) cells - an in vivo study in sheep (317)

Cindy C Shu 1 , Andrew Dart 2 , Elizabeth C Clarke 1 , Joshua Martin 1 , Christopher B Little 1 , James Melrose 1
  1. Kolling Institute of Medical Research, St Leonards, NSW, Australia
  2. University Veterinary Teaching Hospital, University of Sydney, Sydney, NSW, Australia

Introduction: Intervertebral disc (IVD) consists of the collagenous lamellar annulus fibrosus (AF) surrounding the nucleus pulposus (NP), rich in aggrecan that generates hydrostatic pressure and the IVDs complex biomechanical properties. There is no current therapy to reverse IVD degeneration (IVDD), a major cause of chronic lower back pain. We investigated the effects of heterologous bone marrow stem (stromal) cells (BMSC) on a mechanically-induced ovine IVDD model, focusing in this report on the biomechanical/biochemical changes through our mid-long term study. 

Methods: Partial thickness AF incisions were made in 3-year-old ovine lumbar discs. Lesion discs were injected intra-NP with 107 heterologous culture-expanded ovine BMSC or PBS 4 or 12 weeks post-injury, sacrificed 12 or 26 weeks post-surgery, providing three study groups: “acute short-term” (inject at 4 weeks, sacrifice at 12 weeks), “acute long-term” (inject at 4 weeks, sacrifice at 26 weeks) and “established-IVDD” (inject at 12 weeks, sacrifice at 26 weeks). Spine segments underwent biomechanical tests to measure range of motion (ROM) and neutral zone (NZ, displacement where torque equals zero). IVD tissue proteoglycan contents were quantified.

Results: ROM in forward/lateral bending were not different between treatments in any groups. In lesion-PBS compared with non-operated control (NOC), NZ in forward bending was significantly greater at 12 and 26 weeks while in lateral bending was increased at 26 weeks. NZ of BMSC-lesion discs in acute short-term and established-IVDD groups approached NOC levels and significantly lower than PBS-lesion discs. Proteoglycan content in BMSC-NP of established-IVDD group had returned to NOC levels. 

Conclusion: BMSC ameliorated the onset of mechanical IVD failure by restoring the IVDD biomechanical and biochemical properties. Changes in NZ is associated with loss of NP hydration/function coupled with abnormal matrix turnover, evident in NP proteoglycan content. Further investigation on gene expression changes will describe the mechanisms of action by BMSCs.