Cellular and Molecular MRI of Stem Cell Viability

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DESCRIPTION (provided by applicant): An in vivo method to image the engraftment of the transplanted cells in the injured myocardium will enable precise evaluation of cell therapy. Engraftment is a complex cascade of biological processes including cell survival and functional restoration of the recipient tissue. Although MRI has become one of the predominant modalities to track ex vivo labeled cells, definitive information on cellular viability can not be assessed by MRI. In order to address this critical issue, this proposal will describe efforts to implement in vivo cellular and molecular MRI to image viability of transplanted mouse ESC (mESC) and functional restoration of the injured myocardium in murine model of myocardial infarction. To realize this goal, novel MRI methods, innovative cellular and molecular technologies, and a broad array of established methodologies will be integrated for a systematic study of 3 Specific Aims: Specific Aim 1 - In vivo cellular MRI will enable precise evaluation of the viability of transplanted mESC using novel off-resonance MRI sequence. Specific Aim 2 - In vivo molecular MRI of genetically engineered cells will detect viability of transplanted mESC using MRI reporter gene and targeted contrast agent. Specific Aim 3 - Viable mESC will enhance functional restoration of the injured myocardium. This research proposal brings together multidisciplinary investigation in cardiovascular imaging and stem cell biology. This approach has enabled a convergence of innovative approaches in MRI and stem cell biology to address a critical fundamental issue: cellular viability following stem cell transplantation into the myocardium. This proposal complements the high spatial and temporal resolution of MRI with cellular and molecular techniques to amplify the sensitivity of MRI. Upon conclusion of this research, an integrated MRI platform will allow dual evaluation of cell viability and myocardial restoration. Studies have demonstrated a critical role of the infarcted myocardium in the development of congestive heart failure (CHF). The incidence of CHF is now reaching epidemic proportions. Embryonic stem cells have demonstrated the ability to restore the injured myocardium. A non-invasive method to assess the survival of transplanted cells will address a fundamental issue in this novel therapeutic option.