title: Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI.
abstract: Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 +/- 1.5 to 4.9 +/- 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 +/- 2.1 to 4.39 +/- 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 +/- 5.2% preinjection to 34.5 +/- 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 +/- 4.7 to 31.9 +/- 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.
authors.affiliation: Division of Cardiology, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Toronto, Ontario, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Graham
authors.forename: Warren D
authors.initials: WD
authors.lastname: Foltz
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Vaags
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ward
authors.forename: Yuesong
authors.initials: Y
authors.lastname: Yang
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.forename: Ram
authors.initials: R
authors.lastname: Vijayaraghavan
authors.forename: Jay S
authors.initials: JS
authors.lastname: Detsky
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Hough
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: Graham A
authors.initials: GA
authors.lastname: Wright
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Dick
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D003287:Contrast Media; D004195:Disease Models, Animal; D052203:Ferrosoferric Oxide; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D007267:Injections; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000637:transplantation*; D020127:Recovery of Function; D012235:Rhodamines; D033581:Stem Cell Transplantation; D013318:Stroke Volume; D013552:Swine; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: C116572:(((4-chloromethyl)benzoyl)amino)-tetramethylrhodamine; D003287:Contrast Media; D005456:Fluorescent Dyes; D012235:Rhodamines; D016650:Fluorescein-5-isothiocyanate; D052203:Ferrosoferric Oxide