Cartilage and bone regeneration using gene-enhanced tissue engineering.
Joint cartilage injury remains a major problem in orthopaedics with more than 500,000 cartilage repair procedures performed yearly in the United States at a cost of hundreds of millions of dollars. No consistently reliable means to regenerate joint cartilage currently exists. The technologies of gene therapy and tissue engineering were combined using a retroviral vector to stably introduce the human bone morphogenic protein-7 complementary deoxyribonucleic acid into periosteal-derived rabbit mesenchymal stem cells. Bone morphogenic protein-7 secreting gene modified cells subsequently were expanded in monolayer culture, seeded onto polyglycolic acid grafts, implanted into a rabbit knee osteochondral defect model, and evaluated for bone and cartilage repair after 4, 8, and 12 weeks. The grafts containing bone morphogenic protein-7 gene modified cells consistently showed complete or near complete bone and articular cartilage regeneration at 8 and 12 weeks whereas the grafts from the control groups had poor repair as judged by macroscopic, histologic, and immunohistologic criteria. This is the first report of articular cartilage regeneration using a combined gene therapy and tissue engineering approach.
Mason
J M
JM
Department of Research, North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA.
Breitbart
A S
AS
Barcia
M
M
Porti
D
D
Pergolizzi
R G
RG
Grande
D A
DA
D000818:Animals; D001672:Biocompatible Materials; D001698:Biomedical Engineering; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D001861:Bone Regeneration; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D018929:Cell Culture Techniques; D020219:Chondrogenesis; D003094:Collagen / Q000096:biosynthesis; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation; D007719:Knee Joint; D008297:Male; D010521:Periosteum; D011100:Polyglycolic Acid; D011817:Rabbits; D012190:Retroviridae; D016212:Transforming Growth Factor beta / Q000235:genetics
C525819:BMP7 protein, human; D001672:Biocompatible Materials; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D011100:Polyglycolic Acid; D003094:Collagen