Cha Charles W, Boden Scott D
Emory Spine Center, Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, Georgia 30033, USA.
Spine (Phila Pa 1976). 2003 Aug 1;28(15 Suppl):S74-84. doi: 10.1097/01.BRS.0000076902.64395.C3.
This article reviews the potential utilization of various growth factors to enhance spinal fusion and outlines the principles of gene therapy and its application to spinal fusion surgery.
Gene therapy offers an exciting new way to potentially deliver growth factors locally in a targeted fashion with physiologic doses. In its current definition, gene therapy is defined as the use of nucleic acid transfer, either RNA or DNA, to treat or prevent a disease. The scope of gene therapy has expanded beyond its initial application as a method of replacing genetic defects, and its potential to facilitate spinal fusions is currently being evaluated.
Gene therapy strategies for spine fusion are appealing because the setting is uniquely suited for genetic manipulation. The intervention is locally applied. Only a short duration of transgene response by the cells is necessary to establish a spine fusion, and a variety of osteoinductive growth factors have been identified and are available for use. Attempts at spine fusion using gene therapy in the lower animals have been successful using both in vivo and ex vivo approaches. Before human clinical trials can be established, further testing is required in more challenging animal models of bone induction such as nonhuman primates. Should a successful clinical program of gene therapy for spine fusion be established, the use of autograft and its associated morbidities could be eliminated. In fact, gene therapy offers the potential for minimally invasive applications that could bypass the need for an open procedure altogether. It is likely that gene therapy will be a powerful therapeutic tool for the spine surgeon in the new millennium.
本文综述了各种生长因子在增强脊柱融合方面的潜在应用，并概述了基因治疗的原理及其在脊柱融合手术中的应用。
基因治疗提供了一种令人兴奋的新方法，有可能以生理剂量将生长因子靶向性地局部递送。按照其目前的定义，基因治疗被定义为使用核酸转移（RNA或DNA）来治疗或预防疾病。基因治疗的范围已超越其最初作为替代基因缺陷的方法的应用，目前正在评估其促进脊柱融合的潜力。
用于脊柱融合的基因治疗策略很有吸引力，因为这种情况特别适合进行基因操作。干预是局部应用的。细胞只需短暂的转基因反应就能建立脊柱融合，并且已经鉴定出多种骨诱导生长因子可供使用。在低等动物中使用基因治疗进行脊柱融合的尝试，无论是体内还是体外方法都已取得成功。在建立人体临床试验之前，需要在更具挑战性的骨诱导动物模型（如非人灵长类动物）中进行进一步测试。如果能建立一个成功的脊柱融合基因治疗临床方案，就可以消除自体移植及其相关的并发症。事实上，基因治疗为微创应用提供了潜力，甚至可能完全无需开放手术。基因治疗很可能会成为新千年脊柱外科医生的有力治疗工具。
