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Muscle-Based Gene Therapy and Tissue Engineering for Treatment of Growth Plate Injuries

Lee, Chang Woo M.D.*; Martinek, Vladimir M.D.*; Usas, Arvydas M.D.*; Musgrave, Doug M.D.*; Pickvance, E. A. M.D.*; Robbins, Paul Ph.D.†; Moreland, Morey S. M.D.*; Fu, Freddie H. M.D.*; Huard, Johnny Ph.D.*†

Trauma

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.

Study conducted at Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

From the *Department of Orthopaedic Surgery, Musculoskeletal Research Center, and the †Department of Molecular Genetics and Biochemistry, Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

Address correspondence and reprint requests to Johnny Huard, Ph.D., Children's Hospital of Pittsburgh, 4151 Rangos Research Center, 3705 Fifth Avenue, Pittsburgh, PA 15213, U.S.A. (e-mail: jhuard@pitt.edu).

The first two authors, Drs. Chang Woo Lee and Vladimir Martinek, have contributed equally to this work.

This work was supported by grants to Dr. Johnny Huard from the National Institutes of Health (NIH, #1P60 AR44811–01) and the Pittsburgh Tissue Engineering Initiative (PTEI). This work was also supported by the William F. and Jean W. Donaldson Chair at Children's Hospital of Pittsburgh.

© 2002 Lippincott Williams & Wilkins, Inc.