title: Magnetic enhancement of cell retention, engraftment, and functional benefit after intracoronary delivery of cardiac-derived stem cells in a rat model of ischemia/reperfusion.
abstract: The efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres were injected into the left ventricular cavity of syngeneic rats during brief aortic clamping. Placement of a 1.3 Tesla magnet ~1 cm above the heart during and after cell injection enhanced cell retention at 24 h by 5.2-6.4-fold when 1, 3, or 5 × 10(5) cells were infused, without elevation of serum troponin I (sTnI) levels. Higher cell doses (1 or 2 × 10(6) cells) did raise sTnI levels, due to microvascular obstruction; in this range, magnetic enhancement did not improve cell retention. To assess efficacy, 5 × 10(5) iron-labeled, GFP-expressing cells were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left anterior coronary artery, with and without a superimposed magnet. By quantitative PCR and optical imaging, magnetic targeting increased cardiac retention of transplanted cells at 24 h, and decreased migration into the lungs. The enhanced cell engraftment persisted for at least 3 weeks, at which time left ventricular remodeling was attenuated, and therapeutic benefit (ejection fraction) was higher, in the magnetic targeting group. Histology revealed more GFP(+) cardiomyocytes, Ki67(+) cardiomyocytes and GFP(-)/ckit(+) cells, and fewer TUNEL(+) cells, in hearts from the magnetic targeting group. In a rat model of ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is safe and improves cell therapy outcomes.
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA 90048, USA. Ke.Cheng@cshs.org
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Malliaras
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.forename: Baiming
authors.initials: B
authors.lastname: Sun
authors.forename: Christiane
authors.initials: C
authors.lastname: Houde
authors.forename: Giselle
authors.initials: G
authors.lastname: Galang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smith
authors.forename: Noriko
authors.initials: N
authors.lastname: Matsushita
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000737:chemistry; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019394:Ki-67 Antigen / Q000378:metabolism; D008280:Magnetics; D008863:Microspheres; D032383:Myocytes, Cardiac / Q000166:cytology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*; D019210:Troponin I / Q000097:blood; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D019394:Ki-67 Antigen; D019210:Troponin I; D049452:Green Fluorescent Proteins; D007501:Iron; D019009:Proto-Oncogene Proteins c-kit