title: Ferritin as a reporter gene for in vivo tracking of stem cells by 1.5-T cardiac MRI in a rat model of myocardial infarction.
abstract: The methods currently utilized to track stem cells by cardiac MRI are affected by important limitations, and new solutions are needed. We tested human ferritin heavy chain (hFTH) as a reporter gene for in vivo tracking of stem cells by cardiac MRI. Swine cardiac stem/progenitor cells were transduced with a lentiviral vector to overexpress hFTH and cultured to obtain cardiospheres (Cs). Myocardial infarction was induced in rats, and, after 45 min, the animals were subjected to intramyocardial injection of ∼200 hFTH-Cs or nontransduced Cs or saline solution in the border zone. By employing clinical standard 1.5-Tesla MRI scanner and a multiecho T2* gradient echo sequence, we localized iron-accumulating tissue only in hearts treated with hFTH-Cs. This signal was detectable at 1 wk after infarction, and its size did not change significantly after 4 wk (6.33 ± 3.05 vs. 4.41 ± 4.38 mm(2)). Cs transduction did not affect their cardioreparative potential, as indicated by the significantly better preserved left ventricular global and regional function and the 36% reduction in infarct size in both groups that received Cs compared with control infarcts. Prussian blue staining confirmed the presence of differentiated, iron-accumulating cells containing mitochondria of porcine origin. Cs-derived cells displayed CD31, α-smooth muscle, and α-sarcomeric actin antigens, indicating that the differentiation into endothelial, smooth muscle and cardiac muscle lineage was not affected by ferritin overexpression. In conclusion, hFTH can be used as a MRI reporter gene to track dividing/differentiating stem cells in the beating heart, while simultaneously monitoring cardiac morpho-functional changes.
authors.affiliation: Sector of Medicine, Scuola Superiore Sant'Anna, Piazza Martiri della Liberta', 56127 Pisa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Campan
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.forename: Giovanni D
authors.initials: GD
authors.lastname: Aquaro
authors.forename: Francesca
authors.initials: F
authors.lastname: Forini
authors.forename: Marco
authors.initials: M
authors.lastname: Matteucci
authors.forename: Laura
authors.initials: L
authors.lastname: Vannucci
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiuppesi
authors.forename: Claudio
authors.initials: C
authors.lastname: Di Cristofano
authors.forename: Michela
authors.initials: M
authors.lastname: Faggioni
authors.forename: Margherita
authors.initials: M
authors.lastname: Maioli
authors.forename: Lucio
authors.initials: L
authors.lastname: Barile
authors.forename: Elisa
authors.initials: E
authors.lastname: Messina
authors.forename: Massimo
authors.initials: M
authors.lastname: Lombardi
authors.forename: Angela
authors.initials: A
authors.lastname: Pucci
authors.forename: Mauro
authors.initials: M
authors.lastname: Pistello
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001052:Apoferritins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D017930:Genes, Reporter / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013552:Swine; D014161:Transduction, Genetic
chemical_list: D000199:Actins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D001052:Apoferritins