title: Magnetic targeting of cardiosphere-derived stem cells with ferumoxytol nanoparticles for treating rats with myocardial infarction.
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.
authors.affiliation: 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.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Vandergriff
authors.affiliation: Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: Taylor M
authors.initials: TM
authors.lastname: Hensley
authors.affiliation: 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.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Henry
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Shen
authors.affiliation: Department of Biology, North Carolina State University, NC, USA.
authors.forename: Shirena
authors.initials: S
authors.lastname: Anthony
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D052203:Ferrosoferric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D020342:Finite Element Analysis; D006334:Heart Function Tests; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D019190:Iron Overload / Q000473:pathology; D060328:Magnetic Phenomena; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D053758:Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology*
chemical_list: D011479:Protamines; D006493:Heparin; D052203:Ferrosoferric Oxide
keywords: Cardiac stem cells; Ferumoxytol; MRI; Magnetic targeting; Myocardial infarction; Superparamagnetic iron oxide nanoparticles