Exogenously regulated stem cell-mediated gene therapy for bone regeneration

Regulated expression of transgene production and function is of great impor tance for gene therapy. Such regulation can potentially be used to monitor and control complex biological processes. We report here a regulated stem c ell-based system for controlling bone regeneration, utilizing genetically e ngineered mesenchymal stem cells (MSCs) harboring a tetracycline-regulated expression vector encoding the osteogenic growth factor human BMP-2. We sho w that doxycycline (a tetracycline analogue) is able to control hBMP-2 expr ession and thus control MSC osteogenic differentiation both in vitro and in vivo. Following in vivo transplantation of genetically engineered MSCs, do xycycline administration controlled both bone formation and bone regenerati on. Moreover, our findings showed increased angiogenesis accompanied by bon e formation whenever genetically engineered MSCs were induced to express hB MP-2 in vivo. Thus, our results demonstrate that regulated gene expression in mesenchymal stem cells can be used as a means to control bone healing.