Non-Viral Gene Delivery to Mesenchymal Stem Cells: Methods, Strategies and Application in Bone Tissue Engineering and Regeneration

Jose      L. Santos; Deepti      Pandita; Joao      Rodrigues; Ana      P. Pego; Pedro      L. Granja; Helena      Tomas

doi:10.2174/156652311794520102

Abstract

Mesenchymal stem cells (MSCs) can be isolated from several tissues in the body, have the ability to selfrenewal, show immune suppressive properties and are multipotent, being able to generate various cell types. At present, due to their intrinsic characteristics, MSCs are considered very promising in the area of tissue engineering and regenerative medicine. In this context, genetic modification can be a powerful tool to control the behavior and fate of these cells and be used in the design of new cellular therapies. Viral systems are very effective in the introduction of exogenous genes inside MSCs. However, the risks associated with their use are leading to an increasing search for non-viral approaches to attain the same purpose, even if MSCs have been shown to be more difficult to transfect in this way. In the past few years, progress was made in the development of chemical and physical methods for non-viral gene delivery. Herein, an overview of the application of those methods specifically to MSCs is given and their use in tissue engineering and regenerative medicine therapeutic strategies highlighted using the example of bone tissue. Key issues and future directions in non-viral gene delivery to MSCs are also critically addressed.

Keywords: Bone tissue engineering, bone regeneration, gene delivery, mesenchymal stem cells, nanomedicine, non-viral vectors, autoimmune diseases, cytokines, lentivirus, retrovirus, musculoskeletal diseases, nuclear membranes, lipoplexes, Lipofection, artificial chromosomes, Polyethylenimine, poly(ethylene glycol), osteogenic media, green fluorescent protein, electroporation, haemophilia, Parkinson's disease, Alzheimer's disease, spinal cord injury, calcium phosphate precipitates, vascular endothelial growth factor, Hyaluronic acid, Hydroxyapatite, Palmitic acid, Poly-L-lysine