Exosome derived from mesenchymal stem cells mediates hypoxia-specific BMP2 gene delivery and enhances bone regeneration

Gene therapy based on non-viral vector has been used to promote the repair of bone damage. However, low transfection efficiency and uncontrollable expression greatly hinder its clinical translation. Exosomes (Exos) have been extensively studied as a promising non-viral delivery carrier recently, while its delivery efficiency for large nucleic acids is low. Here, a novel gene vector was developed by layer-by-layer self-assembly method using polyethyleneimine (PEI) and Exos derived from mesenchymal stem cells (MSCs) to deliver large plasmids efficiently. Moreover, a hypoxia-specific expression plasmid was constructed by combining hypoxia promoter RTP801 and microRNA 877 (miR877) sponge. Experimental results showed that the gene delivery vector based on Exos exhibited high transfection efficiency and low cytotoxicity to MSCs. The hypoxia-specific expression plasmid significantly increased bone morphogenetic protein 2 (BMP2) expression in hypoxic condition and promoted neoangiogenesis. This study may provide a novel method to improve the repair efficiency in bone tissue engineering.