椎间盘退变生物治疗进展

The recent advances in biological therapy for intervertebral disc degeneration

临床上椎间盘退行性疾病在保守治疗基础上,大多数需要通过外科干预达到长期缓解局部疼痛的目的.但由于椎间盘生物力学上的特殊地位,使得如何在保持椎间盘完整性的基础上,促进椎间盘细胞外基质再生的生物治疗方法成为椎间盘退变预防和治疗的研究热点.椎间盘髓核基质数量和成分的改变被认为是椎间盘退变的一个重要原因,目前许多学者试图通过引入各种外源性生长因子、种子细胞、基因以及基因转染的细胞,以期增加髓核细胞外基质含量,恢复II型胶原和蛋白多糖比例,逆转或延缓椎间盘退变的发展进程.

With the continuous exploration of basic research for the pathogeny of intervertebral disc degenerative disease, the causes of intervertebral disc degeneration （the anabolic imbalance initiated by cells, extracellular matrix, growth factors and inflammatory factors） have gradually become explicit. Combining with the ceaseless extending of tissue engineering in the field of orthopedics, more and more clinical and basic researchers attempt to treat the discogenic disease through the exogenous interference in the process of intervertebral disc degeneration, including molecular therapy, cell therapy and gene therapy. In molecular therapy, stimulating endogenous cell activity and delaying the process of intervertebral disc degeneration, researchers attempt to increase the anabolic growth factors through reducing the inflammatory factors such as TNF-a, IL-8 and so on. Exogenous growth factors BMP7, BMP2 and BM14 （GDF5） have also been proved to have the effects of restraining intervertebral disc degeneration. In cell therapy, the researches are mainly on the introduction of exogenous cells and the expansion and replantation of autologous nucleus pulposus cells in vitro. A randomized controlled trial in clinic preliminarily confirms that the transplantation of autologous nucleus pulposus cells plays a role in maintaining the water content in the discs and the matrix content of nucleus pulposus. Gene therapy overcomes the side effects of the exogenous application of the growth factors and inhibition of inflammatory factors, but it has such defects as short-term effects, instability and so on. It gradually becomes the hot point, to which the researchers pay close attention. However, gene therapy should be performed under strict safety guarantee. The successful construction of a novel regulatory system structured by adenos viruses provides a powerful guarantee for the safety of gene therapy. As the carriers of cells, factors and genes, scaffold materials are indispensable in biological therapy. However, the pathogenic mechanism of the intervertebral disc degeneration has not been completely clear, which makes the biological therapy lack of a definite object. Then how to break through the bottlenecks of the biological therapy depends on the further confirmation of the mechanism of the intervertebral disc degeneration. It is also the field that should be focused on and explored by researchers.