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

Abstract

Poor cell homing limits the efficacy of cardiac cellular therapy. The homing peptide, cysteinearginine-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 SIGNIFICANCE STATEMENTPoor cell homing limits the efficacy of cardiac cellular therapy. Fibrin expression after myocardial injury renders fibrin, an ideal target for the delivery of stem cells. In this study, the authors developed fibrin-targeting stem cells for the repair of myocardial injury using cysteine-arginineglutamic acid-lysine-alanine (CREKA) as the targeting moiety. CREKA-modified mesenchymal stem cells (MSCs) exhibited potent fibrin-targeting ability both in vitro and in vivo, highlighting the utility of active fibrin targeting in cardiac cellular therapy.

Targeted neutrophil-mimetic liposomes promote cardiac repair by adsorbing proinflammatory cytokines and regulating the immune microenvironment

“…The biodistribution of Neu-LPs was assessed according to a previous article [ 33 ]. One day after reperfusion, PBS, LPs, or Neu-LPs (0.5 mg/mL, 200 μL) were intravenously injected into MI/R model mice.…”

Recent advances of CREKA peptide-based nanoplatforms in biomedical applications

“…In another study, a stem cell-CREKA-fibrin targeting system was developed for the treatment of myocardial ischemia-reperfusion (MI/R) injury in rats [ 74 ]. Previous studies have found that poor cell homing is a major barrier limiting the efficacy of cardiac cellular therapy.…”

Antithrombotic Therapy by Regulating the ROS‐Mediated Thrombosis Microenvironment and Specific Nonpharmaceutical Thrombolysis Using Prussian Blue Nanodroplets

“…In recent years, CREKA, a peptide that has been the topic of numerous studies, has been applied to specifically bind to fibrin in thrombi and microthrombi in tumor blood vessel walls and has shown promising thrombi and microthrombi targeting effects. [44][45][46] In blood clots in vitro (Figure S13, Supporting Information), less red fluorescence was observed in the PB-PFP@P group. However, the PB-PFP@PC group showed more red fluorescence, which verified the good targeting ability of PB-PFP@PC to target thrombi through the CREKA peptide.…”