Key result
Human ferritin heavy chain-transduced cardiospheres were successfully tracked in vivo by 1.5-T cardiac MRI up to 4 weeks, preserving cardioreparative potential (36% reduction in infarct size).
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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.
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Campan et al. (2011) studied Myocardial infarction. Human ferritin heavy chain (hFTH)-transduced cardiospheres vs. Nontransduced cardiospheres or saline solution was evaluated on In vivo tracking of stem cells by cardiac MRI and infarct size reduction. Human ferritin heavy chain-transduced cardiospheres were successfully tracked in vivo by 1.5-T cardiac MRI up to 4 weeks, preserving cardioreparative potential (36% reduction in infarct size).
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