Abstract 5284: In Vivo MRI Tracking of Cardiosphere-Derived Stem Cells in the Infarcted Rat Heart
Cardiosphere-derived stem cells (CDCs) offer a potential therapy for the infarcted heart, but in vivo methods to confirm their successful administration and retention are required. Here we investigated whether CDCs could be labelled with micron-sized particles of iron oxide (MPIOs) and detected in vivo within the beating, infarcted rat heart using cine-MRI.
Methods. Cardiac stem cells were spontaneously shed from explants of neonatal rat heart tissue, isolated and cultured to form cardiospheres. CDCs were expanded to passage 2, labelled with 0.9 μm fluorescent MPIOs (Bangs Labs; 2 μl/ml for 18 hours), suspended in agarose and imaged using high resolution MR microscopy. Labelled CDCs (1 x 106) were injected into the rat myocardium (n = 5), 10 minutes after coronary artery ligation. Rat hearts were imaged using in vivo cine MRI and ex vivo MR microscopy.
Results. c-kit+ve and CD90+ve CDCs endocytosed approximately 50 MPIOs/cell during overnight incubation (Figure A⇓) and retained the ability to form cardiospheres. High resolution MR microscopy of cells suspended in agarose (Figure B⇓) identified signal voids corresponding to individual MPIO-labelled CDCs. In vivo MR images acquired 2, 6 and 12 weeks after cell administration (Figure C⇓) confirmed successful cell injection and retention. At 14 weeks, signal voids were observed throughout the infarct scar using ex vivo MR microscopy (Figure D⇓).
Conclusions: CDCs labelled with MPIOs form cardiospheres and can be detected both at the single cell level using MR microscopy and in vivo after direct injection using cine-MRI. MPIO-labelling of CDCs allows injection success and CDC-retention to be monitored in the infarcted rat heart.