Mesenchymal stem cell (MSC) implantation has been shown previously to arrest disc degeneration. This study aims to assess the effect of severity of disc degeneration on the ability of MSCs to arrest the degeneration. Disc degeneration was induced in New Zealand white rabbits at lumbar levels by annular puncture. The degeneration was allowed to progress for 1 month (early group) or 7 months (late group), followed by intradiscal injection of autologous MSCs. For disc levels that received MSCs treatment, 1 x 10(5) BrdU-labeled MSCs were injected per disc level. For the early group, MSC-injection had no significant effects on disc height or the progression of disc degeneration. For the late group, although the MSC-injected discs displayed lower disc heights than the control discs, they were significantly less degenerated together with near normal level of proteoglycan in localized areas. This is the first pilot study to demonstrate that severity of degeneration can influence the therapeutic effect of MSCs. Future studies of cell-based intervertebral disc regeneration should be carefully controlled in the context of stage of disc degeneration.