Neo-angiogenesis of hMSCs transfected with both peptide and genes loaded/coated PLGA nanoparticles

摘要

In angiogenesis, several kinds of specific factors are involved in the vessel formation. For the formation of new vessel structures, we fabricated a specific vehicle carrying co-factors of the peptide and gene that was internalized into human mesenchymal stem cells (hMSCs). The peptde loaded and gene coated non-toxic PLGA nanoparticles (NPs) allowed to be easily entered into hMSCs without cytotoxicity. The negatively charged outer surface of PLGA NPs can be easily complexed with highly positive charged polyethylenimine (PEI) for delivering the genes into cells. This changed surface with PEI of PLGA NPs can be coated with angiogenesis-related plasmid DNA (pDNA) which carrying the negative charges. Also, PLGA NPs can be loaded angiogenesis-related drug of apeline peptide in the core of them. The physical characteristics of PLGA NPs loaded and coated with peptide and genes were determined by the size distribution, gel retardation, and morphologies of them. The PLGA NPs containing apelin peptide and complexing VEGF165 pDNA transfected into hMSCs have been affected to differentiate into endothelial cells and finally formed vascular formation in Matrigel gels in vitro test. Both peptides and genes entered into the internal site of hMSCs using PLGA NPs accelerated the neo-vascularization formation in a limb ischemia animal model. Specific peptide and gene transfected MSCs were switched into endothelial cells and finally formed vessel formation in an animal model.