Smooth muscle cells, but not myocytes, of host origin in transplanted human hearts

Abstract

Background: There is increasing evidence to support a role for stem cells in the regeneration and repair of the human cardiovascular system. However, significant controversy still remains about the extent of chimerism present in blood vessels and myocytes of transplanted human hearts.

Methods and results: We investigated the contribution of infiltrating host cells to human cardiac allografts by evaluating the origin of vascular smooth muscle cells and cardiac myocytes in hearts after orthotopic cardiac transplantation. Smooth muscle cells were identified in pathological human coronary artery specimens with antibodies against smooth muscle alpha-actin. DNA in situ hybridization for the human Y chromosome was then performed on the same samples to identify cells of male origin. Both myocytes and vascular smooth muscle cells were examined for the presence of the Y chromosome in sex-mismatched specimens. In positive control samples, 34.7% of nuclei contained a detectable Y chromosome; in sex-mismatched samples, 2.6% of the smooth muscle cells examined were of host origin. The Y chromosome in myocyte nuclei in male positive controls was detected; however, despite examination of >6000 myocyte nuclei in sex-mismatched specimens, we were unable to detect any nuclei with the clear presence of the Y chromosome.

Conclusions: Vascular smooth muscle cells of infiltrating host cell origin can be found in human cardiac allografts. However, unlike prior reports, we found no evidence that chimerism is present in cardiac myocytes.