Theranostic effect of serial manganese‐enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma

Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn2+) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T1 shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn2+. Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl2 intraperitoneally three times a week. The control group was given MnCl2 only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl2 enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn2+. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.