Muscle-based gene therapy and tissue engineering for treatment of growth plate injuries.
Growth plate injuries may lead to a progressive angular deformity or longitudinal growth disturbance. The authors investigated the feasibility of gene therapy and tissue engineering based on autologous muscle-and adenoviral-mediated gene transfer of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) to treat tibial physeal defects in rabbits. The medial half of the left proximal tibial growth plate was completely excised in 44 6-week-old New Zealand white rabbits. Four experimental groups were created: no treatment (I), autologous muscle interposition (II), autologous muscle interposition injected with adIGF-1 (III), and autologous muscle interposition injected with adBMP-2 (IV). Radiographic and histologic assessments were obtained postoperatively. Significant tibial shortening and a compact osseous bridge were observed in groups I and IV. Growth plates remained open in groups II and III. This experiment demonstrates that IGF-1 had a supportive effect on physeal chondrocytes, while BMP-2 caused increased osteogenic activity in the injured growth plates.
Lee
Chang Woo
CW
Department of Orthopaedic Surgery, Musculoskeletal Research Center,Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania 15213, USA.
Martinek
Vladimir
V
Usas
Arvydas
A
Musgrave
Doug
D
Pickvance
E A
EA
Robbins
Paul
P
Moreland
Morey S
MS
Fu
Freddie H
FH
Huard
Johnny
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D018014:Gene Transfer Techniques; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D011817:Rabbits; D000072042:Salter-Harris Fractures; D013977:Tibia / Q000293:injuries*; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I