title: Externally Applied Static Magnetic Field Enhances Cardiac Retention and Functional Benefit of Magnetically Iron-Labeled Adipose-Derived Stem Cells in Infarcted Hearts.
abstract: : Although adipose-derived stem cells (ASCs) hold the promise of effective therapy for myocardial infarction, low cardiac retention of implanted ASCs has hindered their therapeutic efficiency. We investigated whether an externally applied static magnetic field (SMF) enhances cardiac localization of "magnetic" cells and promotes heart function recovery when ASCs are preloaded with superparamagnetic iron oxide (SPIO) nanoparticles. The influence of SMF (0.1 Tesla) on the biological activities of SPIO-labeled ASCs (SPIOASCs) was investigated first. Fifty-six female rats with myocardial infarction underwent intramyocardial injection of cell culture medium (CCM) or maleSPIOASCs with or without the subcutaneous implantable magnet (CCM-magnet orSPIOASC-magnet). Four weeks later, endothelial differentiation, angiogenic cytokine secretion, angiogenesis, cardiomyocyte apoptosis, cell retention, and cardiac performance were examined. The 0.1-Tsela SMF did not adversely affect the viability, proliferation, angiogenic cytokine secretion, and DNA integrity ofSPIOASCs. The implantedSPIOASCs could differentiate into endothelial cell, incorporate into newly formed vessels, and secrete multiple angiogenic cytokines. Four weeks after cell transplantation, the number of cardiacSPIOASCs was significantly increased, vascular density was markedly enlarged, fewer apoptotic cardiomyocytes were present, and heart contractile function was substantially improved in theSPIOASC-magnet treated rats in comparison with theSPIOASC-treated rats. TheSPIOASCs could differentiate into endothelial cells, incorporate into vessels, promote angiogenesis, and inhibit ischemic cardiomyocyte apoptosis. An externally applied SMF offered a secure environment for biological properties ofSPIOASCs, increased the cardiac retention of implanted magneticSPIOASCs, and further enhanced heart function recovery after myocardial infarction.
  
  
  
  This pilot proof-of-concept study suggests that a 0.1-Tesla static magnetic field does not adversely affect the viability, proliferation, angiogenic cytokine secretion, or DNA integrity of the superparamagnetic iron oxide-labeled adipose-derived stem cells (SPIOASCs). Implantation of adipose-derived stem cells promotes myocardial neovascularization and inhibits ischemic cardiomyocyte apoptosis through endothelial differentiation, incorporation into vessels, and paracrine factor secretion. An externally applied static magnetic field enhanced myocardial retention of intramyocardially injected "magnetic"SPIOASCs and promoted cardiac function recovery after myocardial infarction. With further preclinical optimization, this approach may improve the outcome of current stem cell therapy for ischemic myocardial infarction.
authors.affiliation: Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China National Research Council of Canada, Winnipeg, Manitoba, Canada Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada jianwang1030@126.com ganghong.tian@nrc-cnrc.gc.ca.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Research Council of Canada, Winnipeg, Manitoba, Canada Department of Pharmacology and Therapeutics Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.affiliation: National Research Council of Canada, Winnipeg, Manitoba, Canada Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jixian
authors.initials: J
authors.lastname: Deng
authors.affiliation: National Research Council of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Lin
authors.affiliation: National Research Council of Canada, Winnipeg, Manitoba, Canada Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Department of Cardiothoracic Surgery, The Second Affiliated Hospital of University of South China, Hengyang, Hunan, People's Republic of China.
authors.forename: Dayang
authors.initials: D
authors.lastname: Zheng
authors.affiliation: National Research Council of Canada, Winnipeg, Manitoba, Canada Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Division of Cardiac Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Darren H
authors.initials: DH
authors.lastname: Freed
authors.affiliation: National Research Council of Canada, Winnipeg, Manitoba, Canada Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Cardiac Science Program, Institute of Cardiovascular Science, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Arora
authors.affiliation: National Research Council of Canada, Winnipeg, Manitoba, Canada Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada jianwang1030@126.com ganghong.tian@nrc-cnrc.gc.ca.
authors.forename: Ganghong
authors.initials: G
authors.lastname: Tian
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D004195:Disease Models, Animal; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D005434:Flow Cytometry; D060526:Magnetic Fields; D008297:Male; D053768:Metal Nanoparticles; D009203:Myocardial Infarction; D010865:Pilot Projects; D051381:Rats; D055647:Rats, Transgenic; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide
keywords: Adipose-derived stem cells; Cell retention; Myocardial infarction; Static magnetic field; Superparamagnetic iron oxide