Cardiac differentiation of mesenchymal stem cells in sex mis-matched transplanted hearts: self-repair or just a visit?
Authors: Heinrich Sauer, Jürgen Hescheler, Maria Wartenberg
Journal: Cardiovascular Research (2002)

See article by Bayes-Genis et al. [10] ( pages 404 -410)donors and vice versa, provide the opportunity to investiin this issue.gate whether stem cells or tissue-specific precursor cells translocate from the recipient to the graft.Cell migration Currently, a paradigm shift from the widely accepted from the allograft to the recipient results in systemic dogma of the heart being incapable of self-repair is chimerism, whereas cell migration from the host to the occurring.This is mostly owing to recent revolutionary transplanted organ results in chimerism of the organ [11].observations that host-derived stem cells, presumably Allografted female hearts into human male recipients are mesenchymal stem cells derived from the bone marrow, commonly analyzed for cardiac chimerism by determining can be recruited to, encraft within the myocardium and Y chromosome-positive cells from the recipient present in may participate in the regeneration of heart function [1][2][3].the donor heart.The investigation of cardiac chimerism is The apparent plasticity of adult stem cells has prompted elegantly performed by fluorescence in situ hybridization the possibility that bone marrow-derived mesenchymal using Y chromosome-specific hybridization probes correcells could be isolated from patients, sub-cultivated in vitro lated with immunohistochemistry of cardiac specific and reintroduced after occurrence of heart disease.Bone markers.marrow cells and cardiomyocytes are both arising from the The degree of cardiac chimerism is currently a matter of early mesoderm.However, the cardiomyocyte progenitors intensive discussion [12].Bayes-Genis et al. found 1-2% are developed from the lateral plate mesoderm under the mature cardiomyocytes from the host in biopsy specimen.inducing influence of differentiation factors secreted by the This observation is in line with most previous studies adjacent endoderm, whereas the bone marrow is derived which demonstrated that cardiomyocyte chimerism within from the somitic dorsal mesoderm.Despite these differ-an allografted human heart occurs at very low levels, i.e., ences in origin, several studies performed on rodents [3-0.02-1%[13,14].Only the study of Quiani et al.[11] 6], pigs [7] as well as on humans [8,9] have conclusively reported that approximately 30% of transplanted myocardemonstrated that mesenchymal stem cells own the dium is regenerated within 4 to 28 days after allotranspotency to differentiate to a cardiomyocyte phenotype in plantation by stem cell-derived cardiomyocytes originating the adult heart.With the study of Bayes-Genis et al. in this from the recipient.Several reasons may account for the issue [10], further evidence is provided that stem cells, observed differences: human cardiac allografts are infilpresumably mesenchymal stem cells derived from the bone trated with a population of host-derived leukocytes, i.e., marrow, respond to cardiac tissue signals with differentia-macrophages and T lymphocytes within hours of engrafttion towards the cardiac lineage and integration in the ment, which, naturally, results in the occurrence of Y cardiac tissue microarchitecture.In the study of Bayes-chromosomes in the transplanted female cardiac tissue.Y Genis et al. cardiomyocytes originating from recipients of chromosome-positive cardiac cells could have arisen from transplanted hearts were found in sex-mismatch cardiac the small amount of host atrial myocardium typically allografts.Sex-mismatched cardiac transplantation, i.e., retained after cardiac transplantation.A further point that cases in which male patients receive hearts from female should not be underestimated is the possibility of fetal microchimerism, which means that fetal cells pass into the maternal circulation and can survive in the mother for