Skeletal Biotechnology Laboratory, Hebrew University of Jerusalem-Hadassah Medical Campus, Jerusalem, Israel.
Tissue Eng Part B Rev. 2010 Feb;16(1):13-20. doi: 10.1089/ten.teb.2009.0156.
While various problems with bone healing remain, the greatest clinical change is the absence of an effective approach to manage large segmental defects in limbs and craniofacial bones caused by trauma or cancer. Thus, nontraditional forms of medicine, such as gene therapy, have been investigated as a potential solution. The use of osteogenic genes has shown great potential in bone regeneration and fracture healing. Several methods for gene delivery to the fracture site have been described. The majority of them include a cellular component as the carrying vector, an approach known as cell-mediated gene therapy. Yet, the complexity involved with cell isolation and culture emphasizes the advantages of direct gene delivery as an alternative strategy. Here we review the various approaches of direct gene delivery for bone repair, the choice of animal models, and the various outcome measures required to evaluate the efficiency and safety of each technique. Special emphasis is given to noninvasive, quantitative, in vivo monitoring of gene expression and biodistribution in live animals. Research efforts should aim at inducing a transient, localized osteogenic gene expression within a fracture site to generate an effective therapeutic approach that would eventually lead to clinical use.
虽然骨愈合方面存在各种问题，但最大的临床变化是缺乏有效的方法来治疗创伤或癌症引起的肢体和颅面骨的大节段缺损。因此，已经研究了非传统形式的医学，如基因治疗，作为一种潜在的解决方案。成骨基因在骨再生和骨折愈合中的应用显示出巨大的潜力。已经描述了几种将基因递送到骨折部位的方法。其中大多数包括细胞成分作为携带载体，这是一种称为细胞介导基因治疗的方法。然而，细胞分离和培养的复杂性强调了直接基因传递作为替代策略的优势。在这里，我们回顾了用于骨修复的直接基因传递的各种方法、动物模型的选择以及评估每种技术的效率和安全性所需的各种结果测量。特别强调了对活体动物中基因表达和生物分布的非侵入性、定量、体内监测。研究工作应旨在诱导骨折部位内短暂的局部成骨基因表达，以产生有效的治疗方法，最终将导致临床应用。
