Sox9 gene transfer enhanced regenerative effect of bone marrow mesenchymal stem cells on the degenerated intervertebral disc in a rabbit model

• Published in: PloS one 2014-04, Vol.9 (4), p.e93570-e93570
• Main Authors: Sun, Wei, Zhang, Kai, Liu, Guangwang, Ding, Wei, Zhao, Changqing, Xie, Youzhuan, Yuan, Junjie, Sun, Xiaojiang, Li, Hua, Liu, Changsheng, Tang, Tingting, Zhao, Jie
• Format: Article
• Language: English
• Subjects: Animals; Autografts; Biology and life sciences; Biomedical materials; Bone marrow; Bone Marrow Cells - cytology; Bone Regeneration - genetics; Cell Differentiation - genetics; Chitosan; Chondrocytes; Collagen; Degeneration; Differentiation; Engineering and Technology; Extracellular matrix; Feasibility studies; Gels; Gene therapy; Gene transfer; Genetic aspects; Genetic Therapy; Genotype & phenotype; Histology; Hospitals; Humans; Hydrogels; Immunohistochemistry; Intervertebral Disc Degeneration - genetics; Intervertebral Disc Degeneration - pathology; Intervertebral Disc Degeneration - therapy; Intervertebral discs; Laboratories; Magnetic resonance imaging; Medicine; Medicine and Health Sciences; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchyme; Nuclei; Nuclei (cytology); Nucleus pulposus; Physical Sciences; Physiological aspects; Rabbits; Repair; Research and Analysis Methods; Sox9 protein; SOX9 Transcription Factor - genetics; Stem cell research; Stem cells; Studies; Surgery; Tissue engineering; Transplants & implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093570

The 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. Fifty 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. Sox9 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. Sox9 gene transfer could significantly enhance the repair effect of BMSCs on the degenerated discs.