Quantification of MRI signal of transgenic grafts overexpressing ferritin in murine myocardial infarcts

Abstract

The noninvasive detection of transplanted cells in damaged organs and the longitudinal follow-up of cell fate and graft size are important for the evaluation of cell therapy. We have shown previously that the overexpression of the natural iron storage protein, ferritin, permits the detection of engrafted cells in mouse heart by MRI, but further imaging optimization is required. Here, we report a systematic evaluation of ferritin-based stem cell imaging in infarcted mouse hearts in vivo using three cardiac-gated pulse sequences in a 3-T scanner: black-blood proton-density-weighted turbo spin echo (PD TSE BB), bright-blood T(2) -weighted gradient echo (GRE) and black-blood T(2) -weighted GRE with improved motion-sensitized-driven equilibrium (iMSDE) preparation. Transgenic C2C12 myoblast grafts overexpressing ferritin did not change MRI contrast in the PD TSE BB images, but showed a 20% reduction in signal intensity ratio in black-blood T(2) -weighted iMSDE (p < 0.05) and a 30% reduction in bright-blood T(2) -weighted GRE (p < 0.0001). Graft size measurements by T(2) iMSDE and T(2) GRE were highly correlated with histological assessments (r = 0.79 and r = 0.89, respectively). Unlabeled wild-type C2C12 cells transplanted to mouse heart did not change the MRI signal intensity, although endogenous hemosiderin was seen in some infarcts. These data support the use of ferritin to track the survival, growth and migration of stem cells transplanted into the injured heart.