Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, People's Republic of China.
Department of Cardiology, Rizhao Heart Hospital, Rizhao, Shandong, People's Republic of China.
Stem Cells. 2019 May;37(5):663-676. doi: 10.1002/stem.2983. Epub 2019 Mar 12.
Poor cell homing limits the efficacy of cardiac cellular therapy. The homing peptide, cysteine-arginine-glutamic acid-lysine-alanine (CREKA), targets fibrin effectively which is involved in the repair process of tissue injury. Here, we assessed if CREKA-modified stem cells had enhanced fibrin-mediated homing ability resulting in better functional recovery and structural preservation in a rat myocardial injury model. CREKA-modified mesenchymal stem cells (CREKA-MSCs) were obtained via membrane fusion with CREKA-modified liposomes. The fibrin targeting ability of CREKA-MSCs was examined both in vitro and in vivo. Under both static and flow conditions in vitro, CREKA significantly enhanced MSCs binding ability to fibrin clots (2.6- and 2.3-fold, respectively). CREKA-MSCs showed 6.5-fold higher accumulation than unmodified MSCs in injured rat myocardium one day after administration, resulting in better structural preservation and functional recovery. Fibrin is, therefore, a novel target for enhancing homing of transplanted cells to injured myocardium, and the delivery system of fibrin-targeting is on behalf of a universalizable platform technology for regenerative medicine. Stem Cells 2019;37:663-676.
细胞归巢能力差限制了心脏细胞治疗的效果。归巢肽（半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸，CREKA）能有效靶向纤维蛋白，纤维蛋白参与组织损伤的修复过程。在此，我们评估了 CREKA 修饰的干细胞是否具有增强的纤维蛋白介导的归巢能力，从而在大鼠心肌损伤模型中实现更好的功能恢复和结构保存。通过 CREKA 修饰的脂质体与间充质干细胞的膜融合获得 CREKA 修饰的间充质干细胞（CREKA-MSCs）。在体外和体内检测了 CREKA-MSCs 的纤维蛋白靶向能力。在体外的静态和流动条件下，CREKA 分别显著增强了 MSCs 与纤维蛋白凝块的结合能力（分别为 2.6 倍和 2.3 倍）。与未修饰的 MSCs 相比，在给药后 1 天，CREKA-MSCs 在受损的大鼠心肌中的积累增加了 6.5 倍，导致更好的结构保存和功能恢复。因此，纤维蛋白是增强移植细胞归巢到受损心肌的新靶点，而纤维蛋白靶向的递药系统代表了一种可推广的再生医学通用平台技术。《干细胞》2019；37:663-676。
