Masuda Koichi, An Howard S
Department of Orthopedic Surgery, Rush Medical College at Rush University Medical Center, Chicago, Illinois, USA.
Eur Spine J. 2006 Aug;15 Suppl 3(Suppl 3):S422-32. doi: 10.1007/s00586-006-0149-1. Epub 2006 Jul 25.
Clinically, a large number of patients have persistent low back pain attributable to intervertebral disc (IVD) degeneration. After the concept of biologically regenerating the degenerated IVD using growth factor injection was first proposed in early 1990, the advancement of molecular technology to produce recombinant proteins, including growth factors, on an industrial scale accelerated research in this field. The purpose of this review is to summarize the most recent findings of the in vitro and in vivo effects of growth factors on the IVD and, further, to discuss the limitations of growth factor therapy and its clinical implications. In vitro data showed that stimulation of matrix synthesis by growth factors alters the balance of homeostasis by shifting cellular metabolism to the anabolic state. In vivo data using small animals has shown the possibility of using growth factors as a "structural modifying therapy". Based on in vitro and in vivo data previously reported, the clinical application of growth factors by direct injection of protein into the nucleus pulposus or anulus fibrosus was shown to be feasible as a new therapeutic intervention for treatment of disc degeneration. Stimulation of the biological repair process will create a new category of therapy to treat disc degeneration, where no active treatment currently exists, between conservative therapies and more aggressive therapies such as fusion or disc replacement. However, it should be noted that there are several important factors to be taken into consideration. In a relatively advanced degenerative condition, the supply of nutrients is disturbed and stimulation of cellular activity by growth factors may result in an increased demand for nutrients, eventually inducing an adverse event. Further investigations of the optimal environment for growth factor stimulation should be pursued. Growth factor therapy, which has experimental evidence supporting it to be a "structural modifying therapy", may not be a "symptom modifying therapy" that is able to resolve the symptoms associated with pathologic changes. Therefore, further studies on the effect of growth factor therapy on pain are essential to shed light on its therapeutic usefulness for degenerative disc disease.
临床上，大量患者患有因椎间盘（IVD）退变导致的持续性腰痛。1990年初首次提出使用生长因子注射对退变的IVD进行生物再生的概念后，能够大规模生产包括生长因子在内的重组蛋白的分子技术的进步加速了该领域的研究。这篇综述的目的是总结生长因子对IVD的体外和体内作用的最新研究结果，并进一步讨论生长因子治疗的局限性及其临床意义。体外数据表明，生长因子刺激基质合成会通过将细胞代谢转变为合成代谢状态来改变内环境稳态的平衡。使用小动物的体内数据表明了将生长因子用作“结构修饰疗法”的可能性。根据先前报道的体外和体内数据，通过将蛋白质直接注射到髓核或纤维环中来临床应用生长因子被证明是一种可行的新治疗干预措施，用于治疗椎间盘退变。刺激生物修复过程将创造出一种新的治疗椎间盘退变的疗法，在保守疗法和诸如融合或椎间盘置换等更积极的疗法之间，目前尚无有效的治疗方法。然而，应该注意的是，有几个重要因素需要考虑。在相对晚期的退变情况下，营养供应受到干扰，生长因子刺激细胞活性可能会导致对营养的需求增加，最终引发不良事件。应进一步研究生长因子刺激的最佳环境。有实验证据支持生长因子治疗是一种“结构修饰疗法”，但它可能不是一种能够解决与病理变化相关症状的“症状修饰疗法”。因此，进一步研究生长因子治疗对疼痛的影响对于阐明其对退行性椎间盘疾病的治疗效用至关重要。
