Mechanisms of stem cell effects: Insights from MRI

Early results from stem cell trials to treat myocardial infarction have shown promise. Several types of stem cells have moved through phase I trials to demonstrate safety and some at the same time have shown significant potential for myocardial regeneration and functional recovery. The means by which stem cells contribute to improving myocardial function, however, remains unknown. Challenges in labeling stem cells for tracking and fate determination after cell transplantation have precluded establishing whether transplanted stem cell engraftment, expansion after en-graftment, endogenous stem cell activation or a combination of these mechanisms contribute to improved function. Cardiac magnetic resonance imaging (cMRI), due to its inherent capabilities, has emerged as the imaging modality of choice to provide important insights into remodeling of myocardium after stem cell transplantation and its consequences on cardiac function. Of cMRI capabilities, excellent spatial resolution is instrumental in assessment of global and regional function and feasibility of scar quantification sets it apart from other imaging modalities and facilitates critical analysis. These capabilities permit the identification of dysfunctional myocardium and scar and changes in these regions over time. The effect of stem cell therapeutics on dysfunctional myocardium and scar can then be highlighted in longitudinal assessment in clinical trials. This has been demonstrated in the inaugural Phase I SCIPIO trial where patients received autologous C-kit ^Pos cardiac stem cell (CSC) transplantation. Although the global function improved significantly with CSC transplantation, regional/segmental analysis provided crucial insights into the effects of CSCs on the most dysfunctional myocardial segments. Magnetic resonance imaging is also a contending and complementing modality in molecular imaging essential for mechanistic studies.