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Biomaterials. 2014 Oct;35(30):8528-39. doi: 10.1016/j.biomaterials.2014.06.031. Epub 2014 Jul 16.

Magnetic targeting of cardiosphere-derived stem cells with ferumoxytol nanoparticles for treating rats with myocardial infarction.

Author information

1
Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, NC, USA.
2
Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
3
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
4
Department of Biology, North Carolina State University, NC, USA.
5
Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, NC, USA; The Cyrus Tang Hematology Center, Soochow University, Suzhou, China. Electronic address: ke_cheng@ncsu.edu.

Abstract

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(®) (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.

KEYWORDS:

Cardiac stem cells; Ferumoxytol; MRI; Magnetic targeting; Myocardial infarction; Superparamagnetic iron oxide nanoparticles

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