Molecular imaging methods for stem cell therapies

Despite improvements in prevention and treatment, cardiovascular diseases remain the most common cause of death in the industrialised world. Notwithstanding the recent discovery of resident stem cells in the adult mammalian heart, its intrinsic regeneration potential is insufficient to prevent heart failure after a major myocardial infarct. However, the principal ability of stem cells to regenerate injured organs has initiated translational research exploring the therapeutic potential of these cells to prevent heart failure. Despite promising results in pre-clinical experiments, clinical trials reported only marginal improvements. These clinical experiments indicated the safety of cell transplantation but highlighted our lack of mechanistic understanding on several levels. In order gain a better understanding of cellular repair processes, we will need to monitor administered cell populations in vivo and assess their distribution, proliferation and differentiation. This has now become possible via molecular imaging techniques. The application of molecular imaging techniques has shown that only a small fraction of delivered cells engrafts in the injured heart and up to 90% of these cells die within one week after delivery. Such a level of cell loss presents a significant limitation for potential cell therapies as a therapeutic cell concentration may not be reached, excessive cell death may lead to inflammation and decrease the likelihood for cell survival. Improving cell survival will be the first step towards the realisation of functional integration, the primary aim of cellular therapies. My aim is to find out why cells die after delivery. In particular, I would like to address how much of this cell death is due to mechanical cell damage, ischemia, loss of cell-cell / cell-matrix interactions, inflammation or growth factor deprivation. For that, a combination of reporter gene imaging and magnetic resonance imaging with contrast agents specific for inflammation and apoptosis will be used. Once we know why cells die we will be able to devise specific strategies to prevent cell death. This will allow a more meaningful assessment of the therapeutic potential of delivered stem cells and addressing the requirements for in vivo differentiation.