Acceleration of articular cartilage repair by combined gene transfer of human insulin-like growth factor I and fibroblast growth factor-2 in vivo
Acceleration of articular cartilage repair by combined gene transfer of human insulin-like growth factor I and fibroblast growth factor-2 in vivo
复制标题
DOI：
10.1007/s00402-010-1130-3
复制
发表时间：
2010-10-01
影响因子：
2.3
通讯作者：
Cucchiarini, Magali
中科院分区：
文献类型：
--
作者：
Madry, Henning;Orth, Patrick;Cucchiarini, Magali
提高填充深层骨软骨缺损的新组织的生物化学和结构质量对于增强关节软骨修复至关重要。我们开发了一种新的分子疗法，以增加关节软骨修复的基础上的联合策略，刺激软骨形成的共同转染的人胰岛素样生长因子I（IGF-I）和成纤维细胞生长因子2（FGF-2）在异种移植模型。coli lacZ基因（lacZ植入物）、人IGF-I基因（IGF-I植入物）或人IGF-I和FGF-2基因（IGF-I/FGF-2植入物）。在体外监测转基因的表达模式21天。将LacZ、IGF-I和IGF-I/FGF-2植入兔股骨髁沟骨软骨缺损处。3周时，对关节软骨修复的质量进行定性和定量评价。结果体外实验显示，IGF-I和IGF-I/FGF-2植入物分泌的相应重组蛋白水平均增加。在体内，共转染的IGF-I/FGF-2植入物的移植增加了修复组织的DNA含量，结论IGF-1和FGF-2联合基因转染促进了软骨下骨的形成，并改善了关节软骨的修复，其程度大于单独使用IGF-1或与lacZ植入物相比。2对软骨缺损的治疗可能比单独应用IGF-I更有益。
Introduction Improving the biochemical and structural qualities of the new tissue that fills deep osteochondral defects is critical to enhance articular cartilage repair. We developed a novel molecular therapy to increase articular cartilage repair based on a combined strategy to stimulate chondrogenesis by co-transfection of the human insulin-like growth factor I (IGF-I) and fibroblast growth factor 2 (FGF-2) in a xenogenic transplantation model.Materials and methods NIH 3T3 cells were transfected with expression plasmid vectors containing a cDNA for the E. coli lacZ gene (lacZ implants), the human IGF-I gene (IGF-I implants) or both the human IGF-I and FGF-2 genes (IGF-I/FGF-2 implants). The expression patterns of the transgenes were monitored in vitro for 21 days. LacZ, IGF-I and IGF-I/FGF-2 implants were transplanted into osteochondral defects in the trochlear groove of rabbits. At 3 weeks, the quality of articular cartilage repair was evaluated qualitatively and quantitatively.Results Both IGF-I and IGF-I/FGF-2 implants secreted increased levels of the corresponding recombinant proteins in vitro. In vivo, transplantation of the co-transfected IGF-I/FGF-2 implants increased the DNA content of the repair tissue, accelerated the formation of the subchondral bone and improved articular cartilage repair in a magnitude that was larger than with IGF-I alone or when compared to lacZ implants.Conclusion These results suggest that gene delivery of a combination of IGF-I and FGF-2 to cartilage defects may be more beneficial than application of IGF-I alone.