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Implantation of juvenile human chondrocytes demonstrates no adverse effect on spinal nerve tissue in rats

Abstract

Purpose

Degenerative disc disease (DDD) is a common disabling condition for millions of individuals. Injection of xenogenic juvenile chondrocytes (XJC) into the disc space has been shown to have a therapeutic potential for disc repair. In the current study, XJC were injected extra-discally on neural structures in an in vivo rat hemilaminectomy model to compare the histological and behavioral effects on XJC and fibrin glue carrier.

Methods

Twenty-four rats were assigned to four groups: cells plus carrier, carrier alone, sham hemi-laminectomy, and a positive control (nerve root ligation). A right-sided hemilaminectomy was performed and the study material was placed on and around the exposed L4 nerve root and the spinal cord. Pre- and postoperatively mechanical allodynia was tested on the ipsilateral hind paw using the von Frey up-down method. The lumbar spines were harvested after 6 and 12 weeks for nerve histology and TNF-α quantification.

Results

After a brief period of hyperalgesia, the von Frey data indicate there are no adverse effects of placing XJC on spinal nerve roots in rats. However ligation of nerve root showed significant allodynia compared to the other groups. These behavioral data were supported by histological analyses.

Conclusions

While these results need to be confirmed over a larger period of time, they suggest that XJC transplantation into the disc space shows no adverse effect on nerve tissue.

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Acknowledgments

We would like to thank Prof. Allan I. Basbaum, PhD, FRS and Andrew H. Ahn, MD, PhD from the Department of Anatomy at the University of California, San Francisco for their excellent teaching and training in using the von Frey technique and H. Davis Adkisson, PhD for his critical review and advice.

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Correspondence to Fabrice A. Külling.

Ethics declarations

The Institutional Animal Care Use Committee (IACUC) approved all protocols outlined (AN 07843-01 IACUC).

Conflict of interest

JCL was a consultant for ISTO, all other authors declare to have no conflict of interest.

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Külling, F.A., Liu, J.J., Liebenberg, E. et al. Implantation of juvenile human chondrocytes demonstrates no adverse effect on spinal nerve tissue in rats. Eur Spine J 25, 2958–2966 (2016). https://doi.org/10.1007/s00586-016-4558-5

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  • DOI: https://doi.org/10.1007/s00586-016-4558-5

Keywords

  • Degenerative disc disease
  • Xenogenic juvenile chondrocytes
  • Disc regeneration