Use of muscle cells to mediate gene transfer to the bone defect.
Segmental bone defects and nonunions are relatively common problems facing all orthopaedic surgeons. Osteogenic proteins, i.e., BMP-2, can promote bone healing in segmental bone defects. However, a large quantity of the human recombinant protein is needed to enhance the bone healing potential. Cell mediated gene therapy in the bone defect can allow a sustained expression of the osteogenic proteins and further enhance bone healing. Muscle cells can be easily isolated and cultivated, and they are known to be an efficient gene delivery vehicle to muscle and nonmuscle tissues. Furthermore, they are capable of transforming into osteoblasts when stimulated by BMP-2. Thus, the utilization of muscle cells as the gene delivery vehicle to a bone defect would be an important step in establishing a less invasive treatment for non-unions and segmental bone defects. Muscle cells were transduced when the adenoviral-lacZ vector and injected into the bone defect and the muscles surrounding the defect. Expression of the marker gene was visualized 7 days after the injection, both macroscopically and microscopically, using lacZ histochemistry. The lacZ expressing cells in the defect tissue were also stained for desmin, a muscle specific marker, indicating the presence of muscle cells that have fused into myofibers in this nonmuscle bone defect area. With successful myoblast mediated gene delivery into the segmental bone defect, future experiments would focus on delivering viral vectors expressing osteogenic proteins to eventually improve bone healing postinjury.
Day
C S
CS
Department of Orthopaedic Surgery, Musculoskeletal Research Center, Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Bosch
P
P
Kasemkijwattana
C
C
Menetrey
J
J
Moreland
M S
MS
Fu
F H
FH
Ziran
B
B
Huard
J
J
D000818:Animals; D002460:Cell Line; D016267:External Fixators; D017102:Fracture Healing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology*; D011817:Rabbits; D013978:Tibial Fractures / Q000601:surgery / Q000628:therapy*; D001616:beta-Galactosidase / Q000235:genetics
D001616:beta-Galactosidase