Abstract
Gene transfer to mesenchymal stem cells (MSCs) has arisen as a powerful approach to increase the therapeutic potential of this effective cell population. Over recent years, niosomes have emerged as self-assembled carriers with promising performance for gene delivery. The aim of our work was to develop effective niosomes-based DNA delivery platforms for targeting MSCs. Niosomes based on 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA; 0, 7 or 15%) as cationic lipid, cholesterol as helper lipid, and polysorbate 60 as non-ionic surfactant, were prepared using a reverse phase evaporation technique. Niosomes dispersions (filtered or not) and their corresponding nioplexes with a lacZ plasmid were characterized in terms of size, charge, protection, and complexation abilities. DOTMA concentration had a large influence on the physicochemical properties of resulting nioplexes. Transfection efficiency and cytotoxic profiles were assessed in two immortalized cell lines of MSCs. Niosomes formulated with 15% DOTMA provided the highest values of β-galactosidase activity, being similar to those achieved with Lipofectamine®, but showed less cytotoxicity. Filtration of niosomes dispersions before adding to the cells resulted in a loss of their biological activities. Storage of niosomes formulations (for 30 days at room temperature) caused minor modification of their physicochemical properties but also attenuated the transfection capability of the nioplexes. Differently, addition of the lysosomotropic agent sucrose into the culture medium during transfection or to the formulation itself improved the transfection performance of non-filtered niosomes. Indeed, steam heat-sterilized niosomes prepared in sucrose medium demonstrated transfection capability.
Highlights
Mesenchymal stem cells (MSCs) constitute a pivotal cell population for cell therapy in regenerative medicine
These properties point out MSCs as an excellent target for gene therapy approaches as a way to reinforce their therapeutic potential for tissue repair [3]
di-O-octadecenyl-3-trimethylammonium propane (DOTMA) was included at three levels: 0, 7 and 15 mol% in order to elucidate the effect of the cationic charges on the transfection efficiency
Summary
Mesenchymal stem cells (MSCs) constitute a pivotal cell population for cell therapy in regenerative medicine. Key attributes of MSCs as their capacity to differentiate into various lineages, feasibility of isolation and expansion in vitro, homing and immunomodulatory properties, make them an appealing cell source for tissue repair [1,2]. These properties point out MSCs as an excellent target for gene therapy approaches as a way to reinforce their therapeutic potential for tissue repair [3]. Notwithstanding, gene transfer efficacy via nonviral vectors is still lower when compared with that of their viral counterparts [9,10].
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