Effect of mesenchymal stem cells on myocardial perfusion and function in a rat model of chronic infarction

Background: Despite encouraging preliminar y results of cell-based therapies in patients with ischemic hear t disease there is still a need to develop animal models where abnormalities of myocardial perfusion and left ventricular function can be quantified precisely and followed on a long term basis. Pinhole gated SPECT allows rapid, reproducible and repeatable measurements of myocardial perfusion and function in rats. Aim: To evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on myocardial perfusion and function in a rat model of chronic infarction. Methods: 111Indium-oxine labeled autologous BMSCs were injected within the infarct area in 11 male Wistar rats 3 months after the surgical ligature of the left anterior descending coronar y ar ter y. One animal died during the transplantation. The distribution of the implanted cells was determined by dual isotope (111InThe distribution of the implanted cells was determined by dual isotope (111In and 99mTc-sestamibi) pinhole SPECT performed 2 days later. Myocardial perfusion and left ventricular function were calculated by 99mTc-sestamibi pinhole gated SPECT obtained before, and 1 and 3 months after cell transplantation. Polar maps of myocardial perfusion were generated. Perfusion abnormalities with values below 2 SD of a normal database were defined as infarct areas. Left ventricular volumes and ejection fraction were quantified from the gated data using an automatic program (Univ. of Michigan). Results: Transplanted cells were clearly visualized within the infarct area in all animals. Perfusion defect size ranged from 3 to 47% of the left ventricular surface before transplantation. Perfusion normalized in 1 animal, improved in 3 and was unchanged or deteriorated in the remaining 7 animals. No significant changes in left ventricular volumes and ejection fraction were observed except in the animal in whom perfusion was normalized. Conclusion: Pinhole (gated) SPECT is useful to assess the intra-myocardial distribution of transplanted cells and to monitor the effects of cell-based therapies in rats.