Summary Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.

Recently, it has been demonstrated that oxygen-weighted images of whole blood can be obtained with steady-state methods. In this article, based on computational and experimental models, we investigate the potential for employing this technique to monitor oxygen changes in microcirculation. Results show that oxygen-sensitive images of rabbit kidney and muscle may be obtained at high signal-to-noise ratio within a few seconds. The results also show that in steady-state free precession imaging, in addition to the exchange mechanism that generates oxygen contrast in blood, there are additional mechanisms that provide oxygen-sensitive contrast in microcirculation. Magn Reson Med 55:1372-1380, 2006.