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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. S tem  C ells   2019;37:663–676

Modification with CREKA Improves Cell Retention in a Rat Model of Myocardial Ischemia Reperfusion