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

Abstract

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. 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. 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. 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.