Allogeneic Articular Chondrocyte Transplantation Downregulates Interleukin 8 Gene Expression in the Degenerating Rabbit Intervertebral Disk In Vivo

Am J Phys Med Rehabil. 2015 Jul;94(7):530-8. doi: 10.1097/PHM.0000000000000194.

Abstract

Objective: The aim of this study was to investigate whether repopulating the degenerating intervertebral disk (IVD) with articular chondrocytes will decrease inflammation in the degenerating rabbit IVD.

Design: This was a biologic study in a rabbit IVD-injury model in vivo. Dual cell tracking methods (infrared dye labeling and adenovirus transduction) were used to demonstrate the viability of allogeneic articular chondrocytes injected into degenerating rabbit IVDs. Interleukin 8 gene expression was determined via real-time polymerase chain reaction. Infiltrating inflammatory cells (macrophages, T cells, or neutrophils) were examined with immunohistochemistry. The IVDs were also examined by routine histology.

Results: Articular chondrocytes labeled with infrared dye were detected in the degenerating IVDs at both 2 and 8 wks after injection. At the 2-wk time point, interleukin 8 gene expression was comparable in IVDs injected with chondrocytes and in intact disks as control (P = 0.647), whereas its expression in IVDs injected with saline increased 50-fold (P = 0.028). Transgene expression of red fluorescent protein, β-galactosidase, and human bone morphogenetic protein 7 diminished at 8 wks after injection. IVDs injected with chondrocytes overexpressing human bone morphogenetic protein 7 did not show lower interleukin 8 gene expression or improved histology. Macrophages were consistently detected by immunohistochemistry in the cartilage formed around the needle insertion sites in both the saline and chondrocyte groups, whereas neither T cells nor neutrophils were detected.

Conclusions: Allogeneic rabbit articular chondrocyte survived in the degenerating rabbit IVDs for at least 8 wks. Cell treatment resulted in reduced IVD inflammation but did not significantly improve IVD structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Animals
  • Bone Morphogenetic Protein 7 / genetics*
  • Cell Transplantation / methods
  • Chondrocytes / transplantation*
  • Disease Models, Animal
  • Down-Regulation
  • Gene Expression Regulation*
  • Graft Rejection
  • Graft Survival
  • Humans
  • Interleukin-8 / genetics*
  • Intervertebral Disc Degeneration / genetics*
  • Intervertebral Disc Degeneration / surgery*
  • Rabbits
  • Random Allocation
  • Real-Time Polymerase Chain Reaction / methods
  • Sensitivity and Specificity

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Interleukin-8