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. © The American Society of Gene and Cell Therapy.