Rationale: The methods so far utilized to localize implanted stem cells by cardiac magnetic resonance imaging (MRI) rely on the use of iron oxide nanoparticles. Objective: To test human ferritin heavy chain (hFTH) as a reporter gene for in vivo tracking of stem cells by cardiac MRI. Methods and Results: 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 minutes, the animals were subjected to intramyocardial injection of ~200 hFTH-Cs, or ~200 non-transduced Cs or sterile saline solution in the viable myocardium bordering the infracted area. By employing clinical standard 1.5 Tesla MRI scanner and a multiecho T2* gradient echo sequence, we could localize iron-accumulating tissue only in hearts treated with hFTH-Cs. This signal was detectable at 1 week after infarction and its size did not change significantly after 4 weeks (6.33±3.05 vs 4.41±4.38 mm2). Cell transduction did not affect their regenerative potential, as indicated by significantly better preserved left ventricular global and regional function and a smaller infarct size in both groups of animals that received Cs compared to saline. Prussian blue staining of tissue sections confirmed the presence of differentiated, iron-accumulating CD31 and α-smooth muscle positive cells containing mitochondria of porcine origin; iron accumulation was observed only in rare, scattered macrophages. Conclusions: 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.
Stem Cells Transduction With Ferritin as a Reporter Gene to Track Their Fate by 1.5 Tesla MRI, in the Beating Heart
PISTELLO, MAURO;
2009-01-01
Abstract
Rationale: The methods so far utilized to localize implanted stem cells by cardiac magnetic resonance imaging (MRI) rely on the use of iron oxide nanoparticles. Objective: To test human ferritin heavy chain (hFTH) as a reporter gene for in vivo tracking of stem cells by cardiac MRI. Methods and Results: 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 minutes, the animals were subjected to intramyocardial injection of ~200 hFTH-Cs, or ~200 non-transduced Cs or sterile saline solution in the viable myocardium bordering the infracted area. By employing clinical standard 1.5 Tesla MRI scanner and a multiecho T2* gradient echo sequence, we could localize iron-accumulating tissue only in hearts treated with hFTH-Cs. This signal was detectable at 1 week after infarction and its size did not change significantly after 4 weeks (6.33±3.05 vs 4.41±4.38 mm2). Cell transduction did not affect their regenerative potential, as indicated by significantly better preserved left ventricular global and regional function and a smaller infarct size in both groups of animals that received Cs compared to saline. Prussian blue staining of tissue sections confirmed the presence of differentiated, iron-accumulating CD31 and α-smooth muscle positive cells containing mitochondria of porcine origin; iron accumulation was observed only in rare, scattered macrophages. Conclusions: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
