Myoblast-mediated gene transfer to the joint
Myoblast-mediated gene transfer to the joint
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DOI：
10.1002/jor.1100150616
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发表时间：
1997-11-01
影响因子：
2.8
通讯作者：
Huard, J
中科院分区：
文献类型：
--
作者：
Day, CS;Kasemkijwattana, C;Huard, J
肌肉骨骼系统的一些遗传性和获得性病理情况，如关节炎和韧带、软骨和半月板的损伤，可能适合基因治疗。尽管滑膜细胞的体外基因转移已经被证明可以将抗关节炎蛋白编码的基因转移到兔膝关节，但其成功受到瞬时转基因表达的限制。在这项研究中，使用肌肉细胞作为关节的替代基因载体，在新生兔和成年严重联合免疫缺陷小鼠中进行了数据调查。我们证明，在体外使用相同的腺病毒制剂，成肌细胞比滑膜细胞更有效地被转导。在关节内注射后，工程化的肌肉细胞附着在关节的几个结构上，包括韧带、关节囊和滑膜。此外，注射后5天，新生兔关节不同部位的成肌细胞融合形成许多有丝分裂后的肌管和肌纤维。在成年小鼠的膝盖上，成肌细胞在注射后至少35天融合并表达报告基因。膝关节中有丝分裂后肌纤维的存在增加了分泌蛋白长期表达的可能性。目前，关节中的许多组织(韧带、半月板和软骨)的固有愈合能力较差，经常需要手术矫正。一种稳定的基因载体运送到关节产生的蛋白质，从而改善这些不同的肌肉骨骼状况，可能会改变这些病理的临床意义。
Several genetic and acquired pathologic conditions of the musculoskeletal system, such as arthritis and damage to ligament, cartilage, and meniscus, may be amenable to gene therapy. Even though ex vivo gene transfer with synovial cells has been shown to deliver genes encoding for anti-arthritic proteins into the rabbit knee joint, its success has been limited by a transient transgene expression. In this study, data were investigated regarding the use of muscle cells as an alternative gene-delivery vehicle to the joint in newborn rabbit and adult severe combined immunodeficiency mice. We demonstrated that myoblasts were transduced more efficiently than synovial cells with use of the same adenoviral preparation in vitro. After intra-articular injection, the engineered muscle cells adhered to several structures in the joint, including the ligament, capsule, and synovium. In addition, myoblasts fused to form many post-mitotic myotubes and myofibers at different locations of the joint of the newborn rabbit 5 days after the injection. In the knee of the adult mouse, myoblasts fused and expressed the reporter gene for at least 35 days after the injection. The presence of post-mitotic myofibers in the knee joint raises the possibility of long-term expression of the secreted protein. Currently, numerous tissues in the joint (ligament, meniscus, and cartilage) have poor intrinsic healing capacity and frequently need surgical corrections. A stable gene-delivery vehicle to the joint producing proteins that ameliorate these different musculoskeletal conditions may change the clinical implications of these pathologies.