Implantation of adipose tissue-derived mesenchymal stem cells in degenerative intervertebral disc of rat: When is the most effective time during the degeneration period

This study aimed to investigate whether stem cell transplantation in acute stage is safe, and determined the relationship between the treatment effects and the degree of intervertebral disc degeneration. IVD rat model was created by needle aspiration. Thirty rats were divided into 5 groups as follow: normal (disc without injury), sham (only disc injury without injection), Day 3 (cell injection at 3 day after disc degeneration), Day 7 (cell injection at 7 day after disc degeneration), and Day 14 (cell injection at 14 day after disc degeneration). Magnetic resonance imaging (MRI) and histological evaluation were performed 4 times, 2 weeks after the degeneration was induced and 2, 4, and 6 weeks after cell transplantation at the level of 3 discs. We also evaluated the expression of the disc regeneration markers, such as aggrecan, collagen II, and SOX-9, by western blotting. Day 3 and Day 7 groups showed significantly lesser reduction of the disc height and better restoration of the MRI signal intensity of the intervertebral disc. In hematoxylin and eosin staining of annulus fibrosus, Day 3 and Day 7 groups showed a better grading than Day 14 group did, according to the Nishimura and Mochida grading system. The results of the western blotting revealed patterns similar to the radiologic findings. We revealed that transplanted ADMSCs promote the regeneration of the nucleus pulposus and extracellular matrix. Additionally, we demonstrated that regenerative stem cell therapy is more effective when applied at relatively early stages of degeneration.