Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2) in vivo
Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2) in vivo
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DOI：
10.1002/jgm.819
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Madry, H
中科院分区：
文献类型：
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作者：
Kaul, G;Cucchiarini, M;Madry, H
背景关节软骨缺损是骨科尚未解决的问题。在本研究中，我们验证了通过微囊化转基因关节软骨细胞移植人成纤维细胞生长因子-2(FGF-2)促进体内软骨缺损区软骨形成的假说。将制得的LacZ或FGF2微球应用于兔膝关节软骨缺损的修复。结果在体外，成纤维细胞生长因子-2能够分泌出具有生物活性的成纤维细胞生长因子-2，使成纤维细胞生长因子-2微球内的细胞数量显著增加。在体内，成纤维细胞生长因子-2持续表达至少3周，而不会导致治疗组间关节液中成纤维细胞生长因子-2浓度的差异。组织学分析显示，在任何时间点，滑膜均未受到不良病理影响。成纤维细胞生长因子-2基因转移增强了11型胶原的表达和软骨形成的个体参数，如新组织的细胞形态和结构。整体关节软骨修复在活体两个时间点均有明显改善。结论局部过表达的成纤维细胞生长因子2可通过促进软骨形成促进软骨缺损的修复，而对滑膜无不良影响。这些结果可能会导致安全的基于基因的治疗人类关节软骨缺陷的发展。版权所有(C)2005 John Wiley&Sons，Ltd.
Background Defects of articular cartilage are an unsolved problem in orthopaedics. In the present study, we tested the hypothesis that gene transfer of human fibroblast growth factor 2 (FGF-2) via transplantation of encapsulated genetically modified articular chondrocytes stimulates chondrogenesis in cartilage defects in vivo.Methods Lapine articular chondrocytes overexpressing a lacZ or a human FGF-2 gene sequence were encapsulated in alginate and further characterized. The resulting lacZ or FGF-2 spheres were applied to cartilage defects in the knee joints of rabbits. In vivo, cartilage repair was assessed qualitatively and quantitatively at 3 and 14 weeks after implantation.Results In vitro, bioactive FGF-2 was secreted, leading to a significant increase in the cell numbers in FGF-2 spheres. In vivo, FGF-2 continued to be expressed for at least 3 weeks without leading to differences in FGF-2 concentrations in the synovial fluid between treatment groups. Histological analysis revealed no adverse pathologic effects on the synovial membrane at any time point. FGF-2 gene transfer enhanced type 11 collagen expression and individual parameters of chondrogenesis, such as the cell morphology and architecture of the new tissue. Overall articular cartilage repair was significantly improved at both time points in vivo.Conclusions The data suggest that localized overexpression of FGF-2 enhances the repair of cartilage defects via stimulation of chondrogenesis, without adverse effects on the synovial membrane. These results may lead to the development of safe gene-based therapies for human articular cartilage defects. Copyright (c) 2005 John Wiley & Sons, Ltd.