Human Bone Marrow versus Adipose-Derived Stem Cells: Influence of Donor Characteristics on Expandability and Implications for Osteogenic Ex Vivo BMP-2 Regional Gene Therapy

Abstract

Novel treatment strategies for segmental bone loss in orthopaedic surgery remain under investigation. Regional gene therapy that involves transduction of mesenchymal stem cells with a lentiviral vector that expresses BMP-2 has gained particular interest as this strategy provides osteogenic and osteoinductive factors for bone growth. In particular, transduced adipose-derived stems cells (ASCs) and bone marrow-derived stem cells (BMSCs) have emerged as the leading candidates for the treatment of segmental defects in preclinical models. The aim of the present study was to evaluate the influence of demographic information on in vitro growth characteristics and bone morphogenetic protein-2 production following lentiviral transduction in a large cohort of human donors. We further sought to assess the effects of ASC harvest site on cell yield and growth characteristics. We evaluated a total of 187 human donors (124 adipose harvests and 63 bone marrow aspirates) in our cohort. We found that across all donors, ASCs demonstrated favorable growth characteristics and could be cultured in vitro more reliably than BMSCs regardless of patient-related factors. Furthermore, we noted that following lentiviral transduction, ASCs produced significantly higher levels of BMP-2 compared to BMSCs. Lastly, despite higher initial cell yields from lipoaspirate, posttransduction BMP-2 production was less than that of infrapatellar fat pad samples. These results support the continued investigation of ASCs as a cellular delivery vehicle for regional gene therapy to deliver osteoinductive proteins to specific anatomic bone repair sites.