Ex Vivo Peptide Decoration Strategies on Stem Cell Surfaces for Augmenting Endothelium Interaction

Ischemic vascular diseases remain leading causes of disability and death. Although various clinical therapies have been tried, reperfusion injury is a major issue, occurring when blood recirculates at the damaged lesion. As an alternative approach, cell-based therapy has emerged. Mesenchymal stem cells (MSCs) are attractive cellular candidates due to their therapeutic capacities, including differentiation, safety, angiogenesis, and tissue repair. However, low levels of receptors/ligands limit targeted migration of stem cells. Thus, it is important to improve homing efficacy of transplanted MSCs toward damaged endothelium. Among various MSC modulations, ex vivo cell surface engineering could effectively augment homing efficiency by decorating MSC surfaces with alternative receptors/ligands, thereby facilitating intercellular interactions with the endothelium. Especially, exogenous decoration of peptides onto stem cell surfaces could provide appropriate functional signaling moieties to achieve sufficient MSC homing. Based on their protein-like functionalities, high modularity in molecular design, and high specific affinities and multivalency to target receptors, peptides could be representative surface-presentable moieties. Moreover, peptides feature a mild synthetic process, enabling precise control of amino acid composition and sequence. Such ex vivo stem cell surface engineering could be achieved primarily by hydrophobic interactions of the cellular bilayer with peptide-conjugated anchor modules and by covalent conjugation between peptides and available compartments in membranes. To this end, this review provides an overview of currently available peptide-mediated, ex vivo stem cell surface engineering strategies for enhancing MSC homing efficiency by facilitating interactions with endothelial cells. Stem cell surface engineering techniques using peptide-based bioconjugates have the potential to revolutionize current vascular disease treatments while addressing their technical limitations.