title: Gene therapy approaches to regenerating bone.
abstract: Bone formation and regeneration therapies continue to require optimization and improvement because many skeletal disorders remain undertreated. Clinical solutions to nonunion fractures and osteoporotic vertebral compression fractures, for example, remain suboptimal and better therapeutic approaches must be created. The widespread use of recombinant human bone morphogenetic proteins (rhBMPs) for spine fusion was recently questioned by a series of reports in a special issue of The Spine Journal, which elucidated the side effects and complications of direct rhBMP treatments. Gene therapy - both direct (in vivo) and cell-mediated (ex vivo) - has long been studied extensively to provide much needed improvements in bone regeneration. In this article, we review recent advances in gene therapy research whose aims are in vivo or ex vivo bone regeneration or formation. We examine appropriate vectors, safety issues, and rates of bone formation. The use of animal models and their relevance for translation of research results to the clinical setting are also discussed in order to provide the reader with a critical view. Finally, we elucidate the main challenges and hurdles faced by gene therapy aimed at bone regeneration as well as expected future trends in this field.
authors.affiliation: Skeletal Biotech Laboratory, The Hebrew University, Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem, Israel. nadavk@ekmd.huji.ac.il
authors.forename: Nadav
authors.initials: N
authors.lastname: Kimelman Bleich
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.forename: Jay R
authors.initials: JR
authors.lastname: Lieberman
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000473:pathology / Q000628:therapy*; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001861:Bone Regeneration / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013123:Spinal Fusion / Q000379:methods; D023822:Tissue Engineering / Q000379:methods
chemical_list: D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins