STEM CELL IMAGING

Molecular imaging of the myocardium to facilitate cardiac stem cell therapy

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 Obiettivo del progetto (Objective)

'In clinical trials, functional benefits of cell therapy for repair of the damaged heart have been moderate and variable. Frequently, only a small fraction of transplanted cells engrafts in injured myocardium. This limits therapeutic efficacy and may explain variability of results. There is a need for improved understanding of therapeutic mechanisms and for improved selection of candidates. Specific noninvasive imaging techniques, which go beyond assessment of structure and function of the heart, are promising new means for improving cell therapy. In this proposal, we aim at developing image-based strategies to facilitate stem cell engraftment. The myocardial microenvironment is considered to be a critical contributor to engraftment. It constitutes a suitable target for molecular imaging. Our central hypothesis is that molecular-targeted radionuclide imaging prior to cell delivery can characterize an optimal biologic environment which is supportive of cell engraftment after delivery, and thus predictive of successful myocardial regeneration. This hypothesis will be tested in 3 specific aims, using an array of noninvasive imaging techniques to characterize myocardial biology, to track stem cells and to determine functional and structural effects of cell delivery. Aim 1 will define the role of tissue perfusion and viability for successful engraftment of bone-marrow derived stem cells. Aim 2 will investigate the role of neurohumoral activation after ischemic damage for successful cardiac stem cell engraftment. And in aim 3, knowledge derived in a rat model in aims 1 and 2 will be translated to a large animal model and clinical camera systems. These studies will provide unique new insights into myocardial regeneration. They will also deliver imaging techniques for assistance in therapeutic decision making. The ultimate goal of the project is to optimize cell therapeutic benefit based on imaging of individual disease biology.'

Introduzione (Teaser)

An EU-funded project in Germany is looking at muscle regeneration following injury. Using advanced microscopy methods, scientists hope to determine the optimal conditions required for successful cell therapy.

Descrizione progetto (Article)

A heart attack also known as myocardial infarction causes tissue necrosis due to prolonged ischaemia. New therapeutic approaches utilise cells to regenerate injured myocardium, however, with variable results. Only a small proportion of the administered cells actually engraft in the tissue, emphasising the need for a better understanding of the overall process.

Seeking to address this issue, the EU-funded 'Molecular imaging of the myocardium to facilitate cardiac stem cell therapy' (STEM CELL IMAGING) project set out to develop a molecular imaging platform for non-invasive monitoring of the mechanisms involved in myocardial repair. The idea is to visualise cell trafficking after therapy and to characterise the microenvironmental conditions required for optimal cell engraftment.

The project activities will focus on cellular metabolism, inflammation and tissue perfusion as prerequisites for cell therapy. To facilitate high-resolution imaging, researchers have installed PET-CT and SPECT-CT scanners which they hope to implement in clinical applications as well.

For evaluating the extent of inflammation they have used specific reagents immediately after myocardial cell injury and characterised the inflammatory events in the infarct region. By targeting specific molecules present on immune cells but absent from normal myocardium, scientists aim to devise a strategy for predicting cell recruitment and subsequent tissue regeneration.

The STEM CELL IMAGING consortium activities will provide unique insights into the process of myocardial regeneration. The new imaging techniques are expected to assist therapeutic decision making in the clinic and ultimately maximise therapeutic benefit on an individual basis.