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

Abstract

Ischemic vascular diseases (IVDs) remain leading causes of disability and death. Although various clinical therapies have been tried, reperfusion injury is the major issue, occurring when the blood recirculates at the damaged lesion. As an alternative approach, cell-based therapy has emerged. Mesenchymal stem cells (MSCs) are attractive cellular candidate 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 efficacies 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 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 into cellular bilayer with peptide-conjugated anchor modules and by covalent conjugation between peptides and membrane-available compartments. 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. Keywords: peptide, surface modification, ex vivo cell surface engineering, stem cell, homing, targeted delivery Impact statement: Ischemic vascular diseases are global health issues. Although stem cells show promise for treatment, a low homing ability is a limitation that restricts their effectiveness. To address this drawback, modification of homing peptides onto stem cells surface can enhance cell migration, homing, and tissue restoration. This review focuses on currently developed ex vivo stem cell surface engineering techniques using peptides to enhance homing for treating ischemic vascular diseases.