Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy

Publication date: Available online 18 October 2017
Source:The Spine Journal
Author(s): Chris D. Daly, Peter Ghosh, Andrew C.W. Zannettino, Tanya Badal, Ronald Shimmon, Graham Jenkin, David Oehme, Kanika Jain, Idrees Sher, Angela Vais, Camilla Cohen, Ronil V. Chandra, Tony Goldschlager
Background ContextNeural compression associated with lumbar disc herniation is usually managed surgically by microdiscectomy. However, 10 – 20% patients re-present with debilitating back pain and approximately 15% require further surgery.PurposeUsing an ovine model of microdiscectomy, the present study investigated the relative potential of pentosan polysulfate primed mesenchymal progenitor cells (pMPCs) or MPC alone implanted into the lesion site, to facilitate disc recovery.Study DesignAn ovine model of lumbar microdiscectomy was used to compare the relative outcomes of administering MPCs or pMPC to the injury site post-surgery.MethodsAt baseline 3T MRI of 18 adult ewes was undertaken followed by annular microdiscectomy at two lumbar disc levels. Sheep were randomized into 3 groups (n = 6). The injured controls received no further treatment. Defects of the treated groups were implanted with a collagen sponge and MPC (5x10⁵ cells) or pMPC (5x10⁵ cells). After six months. 3T MRI, and standard radiography was performed. Spinal columns were dissected, individual lumbar discs sectioned horizontally and Nucleus Pulposus (NP) and Annulus Fibrosus (AF) regions assessed morphological and histologically. The NP and AF tissues were dissected into six regions and analysed biochemically for their proteoglycans (PGs), collagen and DNA content.ResultsBoth the MPC and pMPC injected groups exhibited less reduction in disc height (p<0.05) and lower Pfirrmann grades (p≤0.001) compared to the untreated injury controls, but morphological scores for the pMPC injected discs were lower (p<0.05). The PG content of the AF injury site region (AF1) of pMPC discs was higher than MPC and injury control AF1 (p < 0.05). At the AF1 and contralateral AF2 regions the DNA content of pMPC discs was significantly lower than injured control discs and MPC injected discs. Histological and birefringent microscopy revealed increased structural organization and reduced degeneration in pMPC discs, compared to MPC and the injured controls.ConclusionsIn an ovine model six months after administration of pMPCs to the injury site disc PG content and matrix organization was improved relative to controls suggesting its potential as a post-surgical adjunct for limiting progression of disc degeneration after microdiscectomy.



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