Immunoselected STRO-3+mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs

Laboratory investigation

Peter Ghosh D.Sc. 1 , 2 , Robert Moore Ph.D. 3 , Barrie Vernon-Roberts F.R.C.Path. 3 , Tony Goldschlager Ph.D., F.R.A.C.S. 4 , 2 , Diane Pascoe M.B.B.S., F.R.A.N.Z.C.R. 5 , Andrew Zannettino Ph.D. 6 , Stan Gronthos Ph.D. 7 , 8 , and Silviu Itescu M.D. 1
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  • 1 Mesoblast Ltd.;
  • 4 Department of Neurosurgery, Monash Medical Centre;
  • 5 Department of Radiology, Royal Melbourne Hospital, Melbourne;
  • 2 Ritchie Centre, Monash Institute of Medical Research, Clayton, Victoria;
  • 3 Adelaide Centre for Spinal Research, SA Health;
  • 6 Department of Haematology, Centre for Cancer Biology and
  • 7 Mesenchymal Stem Cell Group, Department of Haematology, SA Pathology, Adelaide; and
  • 8 Centre for Stem Cell Research, Robinson Institute, University of Adelaide, South Australia, Australia
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Object

Chronic low-back pain of discal origin is linked strongly to disc degeneration. Current nonsurgical treatments are palliative and fail to restore the disc extracellular matrix. In this study the authors examined the capacity of ovine mesenchymal precursor cells (MPCs) to restore the extracellular matrix of degenerate discs in an ovine model.

Methods

Three adjacent lumbar discs of 24 adult male sheep were injected intradiscally with chondroitinase-ABC (cABC) to initiate disc degeneration. The remaining lumbar discs were used as normal controls. Three months after cABC injection, the L3–4 discs of all animals were injected with either a high dose (4 × 106 cells, in 12 sheep) or low dose (0.5 × 106 cells, in 12 sheep) of MPCs suspended in hyaluronic acid (HA). The adjacent L4–5 degenerate discs remained untreated; the L5–6 discs were injected with HA only. The animals were euthanized at 3 or 6 months after MPC injections (6 sheep from each group at each time point), and histological sections of the lumbar discs were prepared. Radiographs and MR images were obtained prior to cABC injection (baseline), 3 months after cABC injection (pretreatment), and just prior to necropsy (posttreatment).

Results

Injection of cABC decreased the disc height index (DHI) of target discs by 45%–50%, confirming degeneration. Some recovery in DHI was observed 6 months after treatment in all cABC-injected discs, but the DHI increased to within baseline control values only in the MPC-injected discs. This improvement was accompanied by a reduction in MRI degeneration scores. The histopathology scores observed at 3 months posttreatment for the high-dose MPC–injected discs and at 6 months posttreatment for the low-dose MPC–injected discs were significantly different from those of the noninjected and HA-injected discs (p <0.001) but not from the control disc scores.

Conclusions

On the basis of the findings of this study, the authors conclude that the injection of MPCs into degenerate intervertebral discs can contribute to the regeneration of a new extracellular matrix.

Abbreviations used in this paper:AF = anulus fibrosus; cABC = chondroitinase-ABC; DHI = disc height index; HA = hyaluronic acid (hyaluron); MPC = mesenchymal precursor cell; MSC = mesenchymal stem cell; NP = nucleus pulposus.

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Contributor Notes

Address correspondence to: Peter Ghosh, D.Sc., P.O. Box 35, Brookvale, New South Wales 2100, Australia. email: peter.ghosh@mesoblast.com.

Please include this information when citing this paper: published online March 9, 2012; DOI: 10.3171/2012.1.SPINE11852.

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