Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart

Background - We have investigated the usefulness of a model of cardiac development in a large mammal, sheep, for studies of engraftment of human stem cells in the heart. Methods and Results - Adult and fetal human mesenchymal stem cells were injected intraperitoneally into sheep fetuses in utero. Hearts at late fetal development were analyzed for engraftment of human cells. The majority of the engrafted cells of human origin formed segments of Purkinje fibers containing exclusively human cells. There were no differences in engraftment of human mesenchymal stem cells from adult bone marrow, fetal brain, and fetal liver. On average, 43.2% of the total Purkinje fibers in random areas (n = 11) of both ventricles were of human origin. In contrast, approximate to 0.01% of cardiomyocytes were of human origin. Conclusions - Human mesenchymal stem cells preferentially engraft at high levels in the ventricular conduction system during fetal development in sheep. These findings raise the possibility that stem cells contribute to normal development of the fetal heart.