Therapeutic Delivery of Stromal Cell-Derived Factor-1 for Injury Repair

Abstract

Stromal cell-derived growth factor-1 (SDF1) is a chemokine that is over-expressed at sites of injury and is believed to play an important role in wound repair. At the cellular level, SDF1 regulates the mobilization and trafficking of endothelial progenitors that originate in the bone marrow and functionally contribute to neovascularization and angiogenesis in the wound. Consequently, SDF1 is a potentially interesting therapeutic with the potential to enhance these processes in acute and chronic injuries that otherwise tend to heal poorly, such as spinal cord injury, stroke, myocardial infarction, diabetic skin wounds and acute burns. However, the therapeutic usefulness of SDF1, as many other similar peptide-based growth factors and chemokines, is severely limited due to its short in vivo half-life, as it is rapidly degraded by proteases, which are typically very abundant at the wound site. Several studies have reported methodologies to increase SDF1 in vivo stability by mutating the protease cleavage sites of the molecule. Another approach has been to incorporate the chemokine into biomaterials that shield it from degradation. Yet another approach would be to develop a system that is inherently stable and could be combined with these aforementioned strategies. For example, self-assembled nanoparticles could shield SDF1 (or one of its forms engineered to be more resistant to proteolysis) from proteolysis and then be incorporated into suitable biomaterials. Nanotechnology-based delivery systems have however been used to a very limited extent for SDF1. This paper aims to provide a summary of the various stabilization and delivery methods available for SDF1, some of which have been already used, as well as others that have been used with other bioactive peptides, but would be potentially applicable to SDF1.