In Vivo Molecular Magnetic Resonance Imaging of Human Embryonic Stem Cells in Murine Model of Myocardial Infarction
Statement of Benefit to California:
SYNOPSIS: This research proposal represents an integrated, multidisciplinary approach that combines innovative approaches in MRI and stem cell biology to address a fundamental issue in cell therapy for myocardial restoration: hESC viability following transplantation into the injured myocardium. By combining novel molecular techniques with state-of-the-art MRI technology to achieve high spatial and temporal resolution, the aim of the proposal is to develop an integrated MRI platform that will allow dual evaluation of hESC viability and myocardial restoration. This technology should ultimately be applicable to all human organs. The two aims are 1): to stably transfect hESC with an MRI reporter gene and to assess viability of the cells in vitro. 2): to transplant the transfected hESC into injured mouse myocardium to determine and correlate cell viability and functional restoration. SIGNIFICANCE AND INNOVATION: A well-thought out proposal with a good rationale for molecular imaging. The proposed experiments are explicated appropriately in the research plan. The preliminary imaging work provides proof-of-concept, and suggests that the applicant is poised to improve on current technologies. STRENGTHS: An outstanding young investigator who is part of a very strong multi-disciplinary team proposes an imaginative project with very strong preliminary data. A good understanding of the literature and the challenges involved, along with alternate plans in case the sensitivity is not high enough. A major strength of this proposal is the dual evaluation with MRI and bioluminescence to ascertain whether viable hESC will restore injured myocardium. In addition, provisions for opening the techniques to the community are a strength. WEAKNESSES: Some careless errors in referencing and in the number of animals estimated indicate that the grant was hastily and assembled which detracts somewhat from the overall strength of the proposal. DISCUSSION: This is an "MRI grant with a twist" that has the potential to produce excellent work. The images in the preliminary data are very compelling. The heart is a good choice of organ since cardiac MRI is moving forward quickly. The applicant has a good alternative plan in that they will modify the gene construct to express human CD4 if they don't get sufficient sensitivity for MRI. The proposal's strengths also include looking at both up and down regulation with their reporter, and looking at negative and positive contrast.