Enhanced bone morphogenic protein adenoviral gene delivery to bone marrow stromal cells using magnetic nanoparticle

ABSTRACT

OBJECTIVES: This study investigated the question of whether adenoviral magnetofection can be a suitable method for increasing the efficacy of gene delivery into bone marrow stromal cell (BMSC) and for generation of a high level of bone morphogenic protein (BMP) secretion at a minimized viral titer. MATERIALS AND METHODS: Primary BMSCs were isolated from C57BL6 mice and transduced with adenoviral vectors encoding beta galactosidase or BMP2 and BMP7. The level of BMP secretion, activity of osteoblast differentiation, and cell viability of magnetofection were measured and compared with those of the control group. RESULTS: The expression level of beta galactosidase showed that the cell transduction efficiency of AdLacZ increased according to the increased amount of magnetic nanoparticles. No change in cell viability was observed after magnetofection with 2 microL of magnetic nanoparticle. Secretion of BMP2 or BMP7 was accelerated after transduction of AdBMP2 and 7 with magnetofection. AdBMP2 adenoviral magnetofection resulted in up to 7.2-fold higher secretion of BMP2, compared with conventional AdBMP2-transduced BMSCs. Magnetofection also induced a dramatic increase in secretion of BMP7 by up to 10-fold compared to the control. Use of only 1 multiplicity of infection (moi) of magnetofection with adenoviral transduction of AdBMP2 or AdBMP7 resulted in significantly higher transgene expression compared to 20 moi of conventional adenoviral transduction. CONCLUSION: Magnetic particle-mediated gene transudation is a highly efficient method of gene delivery to BMSCs. Magnetofection can lower the amount of viral particles while improving the efficacy of gene delivery.