Gene therapy for bone repair using human cells: superior osteogenic potential of BMP-2 transduced mesenchymal stem cells derived from adipose tissue compared to bone marrow

Ex vivo regional gene therapy strategies using animal mesenchymal stem cells genetically modified to overexpress osteoinductive growth factors has been successfully used in a variety of animal models to induce both heterotopic and orthotopic bone formation. However, in order to adapt regional gene therapy for clinical applications it is essential to assess the osteogenic capacity of transduced human cells and choose the cell type that demonstrates the best clinical potential. Bone marrow stem cells (BMSC) and adipose-derived stem cells (ASC) were selected in our study for in vitro evaluation, before and after transduction with a lentiviral two-step transcriptional amplification system (TSTA) overexpressing BMP-2 (LV-TSTA-BMP-2) or GFP (LV-TSTA-GFP); cell growth, transduction efficiency, BMP-2 production and osteogenic capacity were assessed. We demonstrated that BMSC were characterized by a slower cell growth compared to ASC. FACS analysis of GFP-transduced cells confirmed successful transduction with the...