Ultrasound-mediated transfection of endogenous stem cells for regenerative medicine

The oscillation of microbubbles has long been hypothesized to provide the opportunity to enhance gene delivery as a result of changes in membrane permeability; however, translationally-relevant therapeutic protocols have not yet been realized. We sought to develop and validate a protocol to transfect endogenous mesenchymal stem cells (MSCs) via the local injection of plasmids and microbubbles and the application of ultrasound. We apply this therapy in a pre-clinical model to solve an important clinical problem — that of healing segmental bone defects. More than two million bone-grafting procedures are performed each year using autografts or allografts and these standard of care therapies have substantial disadvantages.