Positive-contrast cellular MRI of embryonic stem cells for tissue regeneration using a highly efficient T1 MRI contrast agent.

ABSTRACT

PURPOSE: To investigate the feasibility of high-sensitivity cellular MRI of embryonic stem (ES) cells using a novel cell permeable and cell retentive T1 contrast agent. MATERIALS AND METHODS: Mouse ES cells were labeled with a novel manganese porphyrin contrast agent, MnAMP, at 0.1 mM over 2 to 24 h and retained in contrast-free medium for up to 24 h postlabeling. MRI was performed on a 3 Tesla clinical scanner; T1 and T2 relaxation times were measured. Quantification of manganese content was performed using atomic absorption spectroscopy. Viability and proliferation assays were done for the longest labeling interval. Differentiation capacity was assessed using the hanging drop method to direct differentiation toward cardiomyocytes. RESULTS: MnAMP-labeled ES cells exhibited over a fourfold decrease in T1 compared with unlabeled cells, and maintained up to a threefold decrease 24 h postlabeling. Viability and proliferation were not affected. Most importantly, labeled ES cells differentiated into functional cardiomyocytes that exhibited normal contractility patterns. CONCLUSION: MnAMP-based cellular MRI is a very high sensitivity T1 approach for cellular imaging. It has the potential for noninvasive in vivo monitoring of stem cell therapy in cardiac regeneration and other tissue engineering and regenerative medicine applications. J. Magn. Reson. Imaging 2016;441456-1463.