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.
Department of Orthopaedic Surgery, Musculoskeletal Research Center,Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania 15213, USA.
Chang Woo
CW
Lee
Vladimir
V
Martinek
Arvydas
A
Usas
Doug
D
Musgrave
E A
EA
Pickvance
Paul
P
Robbins
Morey S
MS
Moreland
Freddie H
FH
Fu
Johnny
J
Huard
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