Co-electrospray of mesemchymal stem cells and gene with non-viral vector in hydrogel microspheres for enhanced stem cell-based therapy

Abstract

Stem cell-based therapies are promising for treating human tissue loss. Mesenchymal stem cells (MSCs) are increasingly used. After delivery to target, MSCs need to have a suitable environment for differentiation and their fate should be appropriately directed. One approach is to modify MSCs first via gene delivery and then encapsulate genetically engineered MSCs in a carrier for subsequent use, e.g., in tissue engineering. In this study, a one-step co-electrospray process was established for simultaneously encapsulating MSCs and gene with a vector in hydrogel microspheres, providing an environment for localized and high-efficiency gene delivery. Poly(ethylenimine)-poly(sorbate) (PEI-PS) conjugate was synthesized as vector and plasmid DNA encoding enhanced green fluorescence protein (pEGFP) was model gene. PEI-PS/pEGFP complexes at 5:1~15:1 were prepared. Co-electrospray of MSCs and PEI-PS/pEGFP complexes was conducted via coaxial electrospray: inner capillary of coaxial spinneret was fed by a MSC suspension with PEI-PS/pEGFP complexes and outer capillary was fed by a Na-alginate aqueous solution, which led to formation of hydrogel microspheres with PEI-PS/pEGFP complexes and MSCs in the liquid core. Various experiments were conducted subsequently. The gene transfection efficiency was found to be enhanced inside the microsphere environment.