Hum Gene Ther. 2019 Feb 16. doi: 10.1089/hum.2018.054. [Epub ahead of print]

Lentiviral Gene Therapy For Bone Repair Using Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells.

Bougioukli S¹, Saitta B², Sugiyama O³, Tang A⁴, Elphingstone J⁵, Evseenko D⁶, Lieberman JR⁷.

Abstract

Umbilical cord blood (UCB) has been increasingly explored as an alternative source of stem cells for use in regenerative medicine due to several advantages over other stem cell sources, including the need for less stringent HLA matching. Combined with an osteoinductive signal, UCB-MSCs could revolutionize the treatment of challenging bone defects. In this study we aimed to develop an ex vivo regional gene therapy strategy using BMP-2-transduced allogeneic UCB-MSCs to promote bone repair. To this end, human UCB-MSCs were transduced with a lentiviral vector carrying the cDNA for BMP-2 (LV-BMP-2). In vitro assays to determine the UCB-MSCs osteogenic potential and BMP-2 production were followed by in vivo implantation of LV-BMP-2-transduced UCB-MSCs in a mouse hind limb muscle pouch. Non-transduced and LV-GFP-transduced UCB-MSCs were used as controls. Transduction with LV-BMP-2 was associated with abundant BMP-2 production and induction of osteogenic differentiation in vitro. Implantation of BMP-2-transduced UCB-MSCs led to robust heterotopic bone formation 4 weeks post-operatively as seen on radiographs and histology. These results, along with the fact that UCB-MSCs can be easily collected with no donor-site morbidity and low immunogenicity, suggest that UCB might be a preferable allogeneic source of MSCs to develop an ex vivo gene therapy approach to treat difficult bone repair scenarios.