Biodistribution of Lentiviral Transduced Adipose-Derived Stem Cells for “Ex-vivo” Regional Gene Therapy for Bone Repair

Abstract Ex-vivo gene therapy has been shown to be an effective method for treating bone defects in preclinical models. As gene therapy is explored as a potential treatment option in humans, an assessment of the safety profile becomes an important next step. The purpose of this study was to evaluate the biodistribution of viral particles at the defect site and various internal organs in a rat femoral defect model after implantation of human ASCs transduced with lentivirus (LV) with two-step transcriptional activation (TSTA) of bone morphogenetic protein 2 (LV-TSTA-BMP-2). Animals were sacrificed at 4-, 14-, 56-, and 84-days post implantation. Treatment groups included 1) standard dose LV-TSTA-BMP-2 2) high dose LV-TSTA-BMP-2, 3) standard dose LV-TSTA-GFP 4) high dose LV-TSTA-GFP and 5) standard dose nontransduced cells. The viral load was assessed at each timepoint in the defect in ten organs and the defect site. Histology of all organs, ipsilateral tibia, and femur were evaluated at each timepoint. There were nearly undetectable levels of LV-TSTA-BMP-2 transduced cells at the defect site at 84 days and no pathologic changes in any organ at all timepoints. Humana ASCs transduced with LV-TSTA may be a safe and effective treatment option when adopted for us in patients.