Abstract
ObjectiveThe effect of Sox9 on the differentiation of bone marrow mesenchymal stem cells (BMSCs) to nucleus pulposus (NP)-like (chondrocyte-like) cells in vitro has been demonstrated. The objective of this study is to investigate the efficacy and feasibility of Sox9-transduced BMSCs to repair the degenerated intervertebral disc in a rabbit model.Materials and MethodsFifty skeletally mature New Zealand white rabbits were used. In the treatment groups, NP tissue was aspirated from the L2-L3, L3-L4, and L4-L5 discs in accordance with a previously validated rabbit model of intervertebral disc degeneration and then treated with thermogelling chitosan (C/Gp), GFP-transduced autologous BMSCs with C/Gp or Sox9-transduced autologous BMSCs with C/Gp. The role of Sox9 in the chondrogenic differentiation of BMSCs embedded in C/Gp gels in vitro and the repair effect of Sox9-transduced BMSCs on degenerated discs were evaluated by real-time PCR, conventional and quantitative MRI, macroscopic appearance, histology and immunohistochemistry.ResultsSox9 could induce the chondrogenic differentiation of BMSCs in C/Gp gels and BMSCs could survive in vivo for at least 12 weeks. A higher T2-weighted signal intensity and T2 value, better preserved NP structure and greater amount of extracellular matrix were observed in discs treated with Sox9-transduced BMSCs compared with those without transduction.ConclusionSox9 gene transfer could significantly enhance the repair effect of BMSCs on the degenerated discs.
Highlights
Degenerative disc disease (DDD) is considered one of the major causes of low back pain [1]
Sox9 could induce the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in C/Gp gels and BMSCs could survive in vivo for at least 12 weeks
It gradually decreased over time, the expression of Sox9 was higher in Sox9-transduced BMSCs than in green fluorescent protein (GFP)-transduced BMSCs at all time points (Fig. 1B)
Summary
Degenerative disc disease (DDD) is considered one of the major causes of low back pain [1]. Intervertebral disc degeneration (IVDD) is characterised by a decrease in the function and number of viable cells in the disc, accompanied by a reduction in the synthesis of extracellular matrix (ECM) components such as aggrecan and type II collagen [2]. Cell-based tissue engineering, which aims to restore IVD structure and function, represents a promising approach to IVD repair or regeneration. The harvest of NP cells from normal discs could induce degeneration in the donor disc [4], whereas cells derived from degenerative discs show an altered phenotype, increased senescence [5] and decreased expression of matrix components [2]. As NP cells possess a chondrocyte-like phenotype [6], bone marrow mesenchymal stem cells (BMSCs), which are capable of differentiating into a chondrocyte-like phenotype when appropriately stimulated [7,8], have shown promise as a suitable cell source to be widely used for IVD regeneration [9,10,11]
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