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Magnetic resonance imaging of targeted catheter-based implantation of myogenic precursor cells into infarcted left ventricular myocardium

J.érôme Garot, MD, PhD^*,,1,*, Thierry Unterseeh, MD^*,,1, Emmanuel Teiger, MD, PhD, Stéphane Champagne, MD^*,, B.énédicte Chazaud, PhD, Romain Gherardi, MD, PhD, Luc Hittinger, MD, PhD^*,, Pascal Guéret, MD, FACC and Alain Rahmouni, MD^||

^* INSERM U 400, Créteil, France
Fédération de Cardiologie, Créteil, France
Explorations Fonctionnelles and INSERM U492, Créteil, France
INSERM E00-11, Créteil, France
^|| Département de Radiologie, Henri Mondor University Hospital, AP-HP, Créteil, France

View larger version (39K): [in a new window]   Figure 1 (A) Short-term toxicity of nanoparticles of iron oxide (Endorem) towards myogenic precursor cells (MPC) was evaluated immediately after incubation with various Endorem concentrations (0 to 4 mg iron/106 cells) and during different incubation times (4 to 36 h). Cell viability was determined with the WST-1 Roche Diagnostics proliferation kit (Manheim, Germany). The optical density represents mitochondrial enzymatic activity that is proportional to the number of viable cells. There was no evidence of short-term toxicity of Endorem towards MPC. (B) Long-term toxicity of Endorem towards MPC that were incubated with 4 mg iron/106 cells during 24 h. Cell viability was evaluated at 3- to 20-day cultures using the WST-1 kit. Results are expressed as mean optical density ± SD of two experiments performed in triplicate. Compared with control (white bars), there was no evidence of long-term toxicity of Endorem (gray bars) towards MPC in culture. OD = optical density.

View larger version (71K): [in a new window]   Figure 2 (A) Left ventricular (LV) voltage map in a healthy animal in which three percutaneous catheter-based injections of iron-loaded myogenic precursor cells (MPC) were performed at the LV apex (black dots). (B) Corresponding magnetic resonance imaging 90 min after MPC implantation (long axis and apical short axis black-blood T2-weighted turbo spin echo imaging) showing the three sites of injection (arrows) on the four-chamber view into normal myocardium with good anatomical agreement (two sites of injection were intersected on the two-chamber view, arrows). (C) Corresponding hematoxylin (upper panel) and Perls stain (lower panel) of implanted iron-loaded MPC into healthy apical LV myocardium (x100).

View larger version (69K): [in a new window]   Figure 3 (A) Left ventricular voltage map in an infarct animal in which three percutaneous catheter-based injections of iron-loaded myogenic precursor cells (MPC) were performed into locally damaged myocardium (one in the center and two at the periphery, black dots). (B) Corresponding magnetic resonance imaging 90 min after MPC implantation (long axis black-blood T2 turbo spin echo imaging, upper panel; inversion-recovery true-fisp in the same view, lower panel) showing three sites of injection (arrows) into hyperenhanced damaged tissue with nice anatomical agreement. (C) Corresponding hematoxylin (upper panel) and Perls stain (lower panel) of implanted iron-loaded MPC (arrows) into ischemic myocardium (x100).