title: "Same day" ex-vivo regional gene therapy: a novel strategy to enhance bone repair.
abstract: Ex-vivo regional gene therapy with bone marrow cells (BMCs) overexpressing bone morphogenetic protein-2 (BMP-2) has demonstrated efficacy in healing critical sized bone defects in preclinical studies. The purpose of this preclinical study was to compare the osteoinductive potential of a novel "same day" ex-vivo regional gene therapy versus a traditional two-step approach, which involves culture expansion of the donor cells before implantation. In the "same day" strategy buffy coat cells were harvested from the rat bone marrow, transduced with a lentiviral vector-expressing BMP-2 for 1 hour and implanted into a rat femoral defect in the same sitting. There was no significant difference (P = 0.22) with respect to the radiographic healing rates between the femoral defects treated with the "same day" strategy (13/13; 100%) versus the traditional two-step approach (11/14; 78%). However, the femoral defects treated with the "same day" strategy induced earlier radiographic bone healing (P = 0.004) and higher bone volume (BV) [micro-computed tomography (micro-CT); P < 0.001]. The "same day" strategy represents a significant advance in the field of ex-vivo regional gene therapy because it offers a solution to limitations associated with the culture expansion process required in the traditional ex vivo approach. This strategy should be cost-effective when adapted for human use.
authors.affiliation: New England Musculoskeletal Institute, Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, Connecticut 06030-5456, USA.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Virk
authors.forename: Osamu
authors.initials: O
authors.lastname: Sugiyama
authors.forename: Sang H
authors.initials: SH
authors.lastname: Park
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
authors.forename: Jay R
authors.initials: JR
authors.lastname: Lieberman
mesh_terms: D000818:Animals; D001846:Bone Development; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D001861:Bone Regeneration / Q000235:genetics*; D016025:Bone Transplantation / Q000379:methods; D002478:Cells, Cultured / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D017102:Fracture Healing / Q000235:genetics*; D050723:Fractures, Bone / Q000378:metabolism / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D016086:Lentivirus / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D014161:Transduction, Genetic
chemical_list: D055396:Bone Morphogenetic Protein 2