Phillips Jennifer E, Gersbach Charles A, García Andrés J
Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Biomaterials. 2007 Jan;28(2):211-29. doi: 10.1016/j.biomaterials.2006.07.032. Epub 2006 Aug 22.
Gene therapy has emerged as a promising strategy for the repair and regeneration of damaged musculoskeletal tissues. Application of this paradigm to bone healing has shown enhanced efficacy in preclinical animal studies compared to conventional bone grafting approaches. This review discusses current and emerging virus-based genetic engineering strategies for the delivery of therapeutic molecules which promote skeletal regeneration. Viral gene delivery vectors are discussed in the context of bone repair in order to illustrate the challenges and applications of these methods with tissue-specific examples. Moreover the concepts discussed can be broadly applied to promote healing in a wide range of tissues. We also present important considerations involved in the application of these gene therapy techniques to a variety of osteogenic (e.g. bone marrow-derived cells) and non-osteogenic (e.g. fibroblasts and skeletal myoblasts) cell types. Criteria for the selection of regenerative molecules with soluble versus intracellular modes of action and emerging combinatorial approaches are also discussed. Overall, gene transfer technologies have the potential to overcome limitations associated with existing bone grafting approaches and may enable investigators to design therapies which more closely mimic the complex spatial and temporal cascade of proteins involved in endogenous bone development and repair.
基因治疗已成为修复和再生受损肌肉骨骼组织的一种有前景的策略。与传统骨移植方法相比，将这种模式应用于骨愈合在临床前动物研究中已显示出更高的疗效。本综述讨论了当前以及新兴的基于病毒的基因工程策略，用于递送促进骨骼再生的治疗性分子。在骨修复的背景下讨论病毒基因递送载体，以便通过组织特异性实例说明这些方法的挑战和应用。此外，所讨论的概念可广泛应用于促进多种组织的愈合。我们还介绍了将这些基因治疗技术应用于多种成骨细胞类型（如骨髓来源的细胞）和非成骨细胞类型（如成纤维细胞和骨骼肌成肌细胞）时涉及的重要考虑因素。还讨论了选择具有可溶性与细胞内作用模式的再生分子的标准以及新兴的联合方法。总体而言，基因转移技术有可能克服与现有骨移植方法相关的局限性，并可能使研究人员能够设计出更紧密模拟参与内源性骨发育和修复的复杂蛋白质时空级联反应的疗法。
