Implantation of Adipose Tissue-derived Mesenchymal Stem Cells in Degenerative Intervertebral Disc of Rat: When is the Most Effective time During the Degeneration Period

Abstract

This study aimed to investigate whether stem cell transplantation in acute stage is safe, and determinedthe relationship between the treatment effects and the degree of intervertebral disc degeneration. IVD rat model wascreated 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 7day after disc degeneration), and Day 14 (cell injection at 14 day after disc degeneration). Magnetic resonance imag-ing (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 regen-eration markers, such as aggrecan, collagen II, and SOX-9, by western blotting. Day 3 and Day 7 groups showedsignificantly lesser reduction of the disc height and better restoration of the MRI signal intensity of the intervertebraldisc. In hematoxylin and eosin staining of annulus fibrosus, Day 3 and Day 7 groups showed a better grading thanDay 14 group did, according to the Nishimura and Mochida grading system. The results of the western blottingrevealed patterns similar to the radiologic findings. We revealed that transplanted ADMSCs promote the regenera-tion of the nucleus pulposus and extracellular matrix. Additionally, we demonstrated that regenerative stem cell ther-apy is more effective when applied at relatively early stages of degeneration.