期刊
BIOMATERIALS
卷 35, 期 30, 页码 8528-8539出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.06.031
关键词
Cardiac stem cells; Magnetic targeting; Myocardial infarction; Ferumoxytol; MRI; Superparamagnetic iron oxide nanoparticles
资金
- American Heart Association [12BGIA12040477]
- NC State University Chancellor's Faculty Excellence Program
- The Education Department of Henan Province Science and Technology Key Project [13A320623]
- National Natural Science Foundation of China [H020381370216]
Stem cell transplantation is a promising therapeutic strategy for acute or chronic ischemic cardiomyopathy. A major limitation to efficacy in cell transplantation is the low efficiency of retention and engraftment, due at least in part to significant early wash-out of cells from coronary blood flow and heart contraction. We sought to enhance cell retention and engraftment by magnetic targeting. Human cardiosphere-derived stem cells (hCDCs) were labeled with FDA-approved ferumoxytol nanoparticles Feraheme (R) (F) in the presence of heparin (H) and protamine (P). FHP labeling is nontoxic to hCDCs. FHP-labeled rat CDCs (FHP-rCDCs) were intracoronarily infused into syngeneic rats, with and without magnetic targeting. Magnetic resonance imaging, fluorescence imaging, and quantitative PCR revealed magnetic targeting increased cardiac retention of transplanted FHP-rCDCs. Neither infusion of FHP-rCDCs nor magnetic targeting exacerbated cardiac inflammation or caused iron overload. The augmentation of acute cell retention translated into more attenuated left ventricular remodeling and greater therapeutic benefit (ejection fraction) 3 weeks after treatment. Histology revealed enhanced cell engraftment and angiogenesis in hearts from the magnetic targeting group. FHP labeling is safe to cardiac stem cells and facilitates magnetically-targeted stem cell delivery into the heart which leads to augmented cell engraftment and therapeutic benefit. (C) 2014 Elsevier Ltd. All rights reserved.
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