Park Hee Won, Lee Chae Eun, Kim Sungjun, Jeong Woo-Jin, Kim Kyobum
Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Republic of Korea.
Department of Biological Engineering, Inha University, Incheon, Republic of Korea.
Tissue Eng Part B Rev. 2024 Jun;30(3):327-339. doi: 10.1089/ten.TEB.2023.0210. Epub 2023 Nov 15.
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, 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 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, 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.
缺血性血管疾病仍然是导致残疾和死亡的主要原因。尽管已经尝试了各种临床治疗方法，但再灌注损伤是一个主要问题，当血液在受损病变处重新循环时就会发生。作为一种替代方法，基于细胞的疗法已经出现。间充质干细胞（MSCs）因其治疗能力，包括分化、安全性、血管生成和组织修复，而成为有吸引力的细胞候选物。然而，受体/配体水平较低限制了干细胞的靶向迁移。因此，提高移植的间充质干细胞向受损内皮细胞的归巢效率很重要。在各种间充质干细胞调节方法中，细胞表面工程可以通过用替代受体/配体修饰间充质干细胞表面来有效提高归巢效率，从而促进与内皮细胞的细胞间相互作用。特别是，将肽外源修饰到干细胞表面可以提供适当的功能信号部分，以实现足够的间充质干细胞归巢。基于其类似蛋白质的功能、分子设计中的高模块化以及对靶受体的高特异性亲和力和多价性，肽可以成为具有代表性的可呈递到表面的部分。此外，肽具有温和的合成过程，能够精确控制氨基酸组成和序列。这种干细胞表面工程主要可以通过细胞双层与肽缀合的锚定模块的疏水相互作用以及肽与膜中可用区域之间的共价缀合来实现。为此，本综述概述了目前可用的基于肽的干细胞表面工程策略，这些策略通过促进与内皮细胞的相互作用来提高间充质干细胞的归巢效率。使用基于肽的生物共轭物的干细胞表面工程技术有可能在解决当前血管疾病治疗技术局限性的同时，彻底改变这些治疗方法。
