INTRODUCTION: Disc degeneration is believed to play a major role in chronic lumbar pain patients. Recently, cell migration around stem cells niches in outer parts of the intervertebral disc(IVD) in young rabbits was reported. The aim of this study was to investigate cell migration routes and examine the presence of prechondrocytic cells in the IVD of adult, fully grown mammals.Additionally, to investigate presence of the same markers in human degenerated IVDs.
METHODS: 5‐bromo‐2‐deoxyuridine(BrdU) in vivo‐labelling was performed in 9 New Zealand white rabbits,age 9 months. BrdU incorporation was visualized by immunohistochemistry at different time points providing cell division pattern and presence of slow‐cycling cells in IVDs. Negative controls were non‐labelled rabbits(n=2).Human(n=16), porcine(n=2), lapine(n=5) IVDs were investigated by IHC for: Growth‐and‐differentiation‐factor‐5(GDF5), SOX9(chondrogenic lineage markers), SNAIL‐homolog‐1(SNAI1), SNAIL‐homolog‐2(SLUG)(migration markers) and β1‐INTEGRIN(cellular adhesion marker). Gene expression of the markers was investigated by real‐ time PCR.
RESULTS: BrdU+ cells were observed in early time points in the IVD niches, adjacent to the epiphyseal plate, at later time points mainly in outer region of the annulus fibrosus of the labelled rabbits, indicating a gradual migration of cells. The presence of SLUG, SNAI1, GDF5, SOX9 and β1‐INTEGRIN were detected in the same regions on protein‐and gene expression levels in animal and human IVD regions.
DISCUSSION: The results suggest a cellular migration route from peripheral stem cell niches toward inner parts of the IVD in mature animals in a similar pattern as observed for young, growing animals. The data supports that a remaining pool excists in IVD niches of adult mammals where prechondrocytes are recruited and support normal regeneration of the IVD and disc repair. These findings may be of importance for future development of biological treatment strategies.