Premium
Myoblast‐mediated gene transfer to the joint
Author(s) -
Day Charles S.,
Kasemkijwattana Channarong,
Menetrey Jacques,
Floyd S. Steven,
Booth David,
Moreland Morey S.,
Fu Freddie H.,
Huard Johnny
Publication year - 1997
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100150616
Subject(s) - gene delivery , myogenesis , myocyte , joint capsule , genetic enhancement , cartilage , meniscus , knee joint , microbiology and biotechnology , ex vivo , transgene , pathology , biology , medicine , in vivo , gene , anatomy , surgery , genetics , physics , incidence (geometry) , optics
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.