**7. MSCs in intervertebral disc degeneration**

Intervertebral disc degenerative is a serious worldwide problem for the aging population. The apoptosis of nucleus pulposus cells could be the main cause of intervertebral disc degeneration, with a variety of manifestations, that is, reduced number of the cells, the changes of the mechanical structure, down-regulated synthesis of matrix components (such as proteoglycan), nucleus pulposus dehydration, and increased metabolic waste [56, 57]. Many treatment options have been proposed, including physical therapy, pain medication, epidural steroid drug injection, disc radiating, myeloid nucleation, intervertebral fusion, and intervertebral disc displacement. However, these therapeutic approaches aim only to relieve the symptoms of disc degeneration, not treat its underlying cause. MSCs transplantation provides a new therapeutic strategy for promoting proteoglycan synthesis, decelerating the course of disc degeneration, and stimulating disc regeneration.

For example, Sobajima et al. reported that BMSCs was injected into the lumbar intervertebral disc of the New Zealand white rabbit, and found that the transplanted BMSCs survived and migrated to the fibrous ring after 24 weeks [58]. Hee et al. confirmed that BMSCs implantation and axial distraction may have a synergistic effect in reversing degenerative disc disease in the rabbit model [59]. Some scholars have discovered that drug stimulation can regulate the differentiation of nucleus pulposus MSCs into nucleus pulposus cell by promoting expression of hypoxia-inducible factor to repair and reconstruct degenerated intervertebral disc [60].

In a recent study, under fluoroscopic guidance, the BMCs were injected into the nucleus pulposus of 26 patients' with chronic (>6 months) discogenic low back pain [61]. These authors found the evidence of safety and feasibility in the non-surgical treatment of discogenic pain using autologous BMCs with durable pain relief (71% VAS reduction) and Oswestry Disability Index improvements (>64%) through 2 years.

Overall, the BMSCs as a treatment of degenerated intervertebral disc is successful both in an animal model and in clinical studies; however, there are no long-term follow-up results and the number of reports and the number of cases are still relatively low. Another concern is that, at least in theory, BMSCs may cause osteophyte formation in the vertebral isthmus when it is released from the nucleus. Further clinical trials are needed to clarify these concerns.
