Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model.
Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model.
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DOI：
10.22203/ecm.v025a17
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发表时间：
2013-04-16
影响因子：
3.1
通讯作者：
Cucchiarini M
中科院分区：
文献类型：
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作者：
Madry H;Kaul G;Zurakowski D;Vunjak-Novakovic G;Cucchiarini M
组织工程结合基因治疗是促进关节软骨修复的一种很有前途的方法。在这里，我们测试了一个假设，即软骨细胞过度表达人胰岛素样生长因子I （IGF-I）基因的工程软骨可以增强骨软骨缺陷的修复，其方式取决于培养时间。将转基因软骨细胞置于可生物降解的聚乙醇酸支架上，在动态流动旋转生物反应器中培养10或28 d。将所得软骨构建物植入兔膝关节骨软骨缺损。体内植入28周后，在接受lacZ构建的缺陷修复组织中检测到对ß-gal的免疫反应性。与对照（lacZ）构建体相比，基于igf - i过表达软骨细胞的工程软骨构建体显著改善骨软骨修复。此外，体外培养28 d的IGF-I构建体与体外培养10 d的类似构建体相比，显著促进骨软骨修复-à-vis，导致缺损附近软骨的骨关节炎变化显著减少。因此，在组织工程构建体中，将人类IGF-I的空间定义过表达与长时间的生物反应器培养相结合，可以增强关节软骨的修复，并减少缺损附近软骨的骨关节炎变化。这种基因增强的组织工程提供了一种多功能的工具来评估体内潜在的治疗基因，并提高我们对关节软骨缺损修复组织发育的理解。通过使用该模型进行进一步探索获得的见解可能会为急性软骨缺损提供更有效的治疗选择。
Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.