Muscle-based gene therapy and tissue engineering for treatment of growth plate injuries

被引:21
作者
Lee, CW [1 ]
Martinek, V [1 ]
Usas, A [1 ]
Musgrave, D [1 ]
Pickvance, EA [1 ]
Robbins, P [1 ]
Moreland, MS [1 ]
Fu, FH [1 ]
Huard, J [1 ]
机构
[1] Childrens Hosp Pittsburgh, Rangos Res Ctr 4151, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
关键词
BMP-2; gene therapy; IGF-1; muscle; physeal defect; tissue engineering;
D O I
10.1097/00004694-200209000-00001
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
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.
引用
收藏
页码:565 / 572
页数:8
相关论文
共 40 条
[21]   MANAGEMENT OF PARTIAL GROWTH ARREST - PHYSIS, FAT, OR SILASTIC [J].
LEE, EH ;
GAO, GX ;
BOSE, K .
JOURNAL OF PEDIATRIC ORTHOPAEDICS, 1993, 13 (03) :368-372
[22]   MUSCLE REGENERATION FOLLOWING INJURY CAN BE MODIFIED IN-VIVO BY IMMUNE NEUTRALIZATION OF BASIC FIBROBLAST GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-BETA-1 OR INSULIN-LIKE GROWTH-FACTOR-I [J].
LEFAUCHEUR, JP ;
SEBILLE, A .
JOURNAL OF NEUROIMMUNOLOGY, 1995, 57 (1-2) :85-91
[23]   Regional gene therapy with a BMP-2-producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents [J].
Lieberman, JR ;
Le, LQ ;
Wu, L ;
Finerman, GAM ;
Berk, A ;
Witte, ON ;
Stevenson, O .
JOURNAL OF ORTHOPAEDIC RESEARCH, 1998, 16 (03) :330-339
[24]  
Lipp E J, 1998, Orthop Nurs, V17, P17
[25]   Cartilage-derived morphogenetic proteins - Key regulators in chondrocyte differentiation? [J].
Luyten, FP .
ACTA ORTHOPAEDICA SCANDINAVICA, 1995, 66 :51-54
[26]  
LUYTEN FP, 1992, J BIOL CHEM, V267, P3691
[27]  
MacGregor J, 1996, Can J Appl Physiol, V21, P236
[28]   Direct-, fibroblast- and myoblast-mediated gene transfer to the anterior cruciate ligament [J].
Menetrey, J ;
Kasemkijwattana, C ;
Day, CS ;
Bosch, P ;
Fu, FH ;
Moreland, MS ;
Huard, J .
TISSUE ENGINEERING, 1999, 5 (05) :435-442
[29]   Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone [J].
Musgrave, DS ;
Bosch, P ;
Ghivizzani, S ;
Robbins, PD ;
Evans, CH ;
Huard, J .
BONE, 1999, 24 (06) :541-547
[30]   Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites [J].
Nixon, AJ ;
Fortier, LA ;
Williams, J ;
Mohammed, H .
JOURNAL OF ORTHOPAEDIC RESEARCH, 1999, 17 (04) :475-487