Assessment of cell delivery in cardiac stem cell therapy using PET-MR imaging

Objectives Adipose-derived stem cells (ASC) have promising potential in regenerative medicine and cell therapy. The objective of this study was to define effective cell-delivery methods by non-invasively monitoring the biodistribution of the implanted stem cells in a rat model of congestive heart failure (CHF) using PET and MRI.

Methods Male ASCs were first labeled with 20μg/ml SPIO nanoparticles for 48 hours and then labeled with FDG (~100 μCi/ml) using the protocol developed in our previous study. The rat model of CHF was created with occlusion of LAD in female animals. Immediately, the labeled ASCs were injected (a) into heart muscle (n = 4) or (b) left ventricle (n = 4) or (c) tail vein (n = 4). Whole-body PET and MR images were acquired using a microPET P4 and a 7-Tesla Bruker MRI. The PET images were analyzed and quantified using ASIPro software, to obtain for each organ, the percentage values of the retained cells to the amount implanted. Methods of co-registering PET-MR images were developed for accurate localization of the stem cells. Following the imaging, the animals were euthanized and their vital organs were harvested. Numbers of male stem cells in the organs were then determined using real-time polymerase chain reaction (RT-PCR).

Results Our study showed that the retention of the stem cells in the myocardium depends greatly on the cell delivery method. The preliminary results indicate that 16±5% of the injected cells were retained in the myocardium in group (a), 6± 1% in group (b), and cell retention was minimal in group (c), where 80±5% of the cells were retained in the lungs. Our RT-PCR results confirmed biodistribution of the stem cells determined with the imaging techniques (Figure 1).

Conclusions Multimodality PET-MR imaging is a reliable technique for in vivo, non invasive cell tracking studies and provides a useful tool in assessment of various cell delivery methods.

Research Support CIHR Emerging Team Grant in Regenerative Medicine and Nanomedicine, Health Sciences Department of Research, MHRC, University of Manitoba (Dr. Thorlakson Foundation) and University of Winnipeg, Winnipeg, Canada