title: Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment into, and isolation of viable engrafted donor cells from, the heart.
abstract: Stem cells offer a promising approach to the treatment of myocardial infarction and prevention of heart failure. We have used iron labeling of bone marrow stromal cells (BMSCs) to noninvasively track cell location in the infarcted rat heart over 16 weeks using cine-magnetic resonance imaging (cine-MRI) and to isolate the BMSCs from the grafted hearts using the magnetic properties of the donor cells. BMSCs were isolated from rat bone marrow, characterized by flow cytometry, transduced with lentiviral vectors expressing green fluorescent protein (GFP), and labeled with iron particles. BMSCs were injected into the infarct periphery immediately following coronary artery ligation, and rat hearts were imaged at 1, 4, 10, and 16 weeks postinfarction. Signal voids caused by the iron particles in the BMSCs were detected in all rats at all time points. In mildly infarcted hearts, the volume of the signal void decreased over the 16 weeks, whereas the signal void volume did not decrease significantly in severely infarcted hearts. High-resolution three-dimensional magnetic resonance (MR) microscopy identified hypointense regions at the same position as in vivo. Donor cells containing iron particles and expressing GFP were identified in MR-targeted heart sections after magnetic cell separation from digested hearts. In conclusion, MRI can be used to track cells labeled with iron particles in damaged tissue for at least 16 weeks after injection and to guide tissue sectioning by accurately identifying regions of cell engraftment. The magnetic properties of the iron-labeled donor cells can be used for their isolation from host tissue to enable further characterization.
authors.affiliation: Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford, UK, OX1 3PT.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stuckey
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Carr
authors.forename: Enca
authors.initials: E
authors.lastname: Martin-Rendon
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Tyler
authors.forename: Corinne
authors.initials: C
authors.lastname: Willmott
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cassidy
authors.forename: Sarah J M
authors.initials: SJ
authors.lastname: Hale
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Schneider
authors.forename: Louise
authors.initials: L
authors.lastname: Tatton
authors.forename: Sian E
authors.initials: SE
authors.lastname: Harding
authors.forename: George K
authors.initials: GK
authors.lastname: Radda
authors.forename: Suzanne
authors.initials: S
authors.lastname: Watt
authors.forename: Kiernan
authors.initials: K
authors.lastname: Clarke
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology*; D007501:Iron / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D019028:Magnetic Resonance Imaging, Cine; D009203:Myocardial Infarction / Q000175:diagnosis / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D049452:Green Fluorescent Proteins; D007501:Iron