Federico Quaini, M.D., Konrad Urbanek, M.D., Antonio P. Beltrami, M.D., Nicoletta Finato, M.D., Carlo A. Beltrami, M.D., Bernardo Nadal-Ginard, M.D., Ph.D., Jan Kajstura, Ph.D., Annarosa Leri, M.D., and Piero Anversa, M.D.
Background Cases in which a male patient receives a heart froma female donor provide an unusual opportunity to test whetherprimitive cells translocate from the recipient to the graftand whether cells with the phenotypic characteristics of thoseof the recipient ultimately reside in the donor heart. The Ychromosome can be used to detect migrated undifferentiated cellsexpressing stem-cell antigens and to discriminate between primitivecells derived from the recipient and those derived from thedonor.
Methods We examined samples from the atria of the recipientand the atria and ventricles of the graft by fluorescence insitu hybridization to determine whether Y chromosomes were presentin eight hearts from female donors implanted into male patients.Primitive cells bearing Y chromosomes that expressed c-kit,MDR1, and Sca-1 were also investigated.
Results Myocytes, coronary arterioles, and capillaries thathad a Y chromosome made up 7 to 10 percent of those in the donorhearts and were highly proliferative. As compared with the ventriclesof control hearts, the ventricles of the transplanted heartshad markedly increased numbers of cells that were positive forc-kit, MDR1, or Sca-1. The number of primitive cells was higherin the atria of the hosts and the atria of the donor heartsthan in the ventricles of the donor hearts, and 12 to 16 percentof these cells contained a Y chromosome. Undifferentiated cellswere negative for markers of bone marrow origin. Progenitorcells expressing MEF2, GATA-4, and nestin (which identify thecells as myocytes) and Flk1 (which identifies the cells as endothelialcells) were identified.
Conclusions Our results show a high level of cardiac chimerismcaused by the migration of primitive cells from the recipientto the grafted heart. Putative stem cells and progenitor cellswere identified in control myocardium and in increased numbersin transplanted hearts.
Source Information
From the Department of Medicine, New York Medical College, Valhalla (F.Q., K.U., A.P.B., B.N.-G., J.K., A.L., P.A.); and the Department of Pathology, University of Udine, Udine, Italy (N.F., C.A.B.).
Address reprint requests to Dr. Anversa at the Department of Medicine, Vosburgh Pavilion, New York Medical College, Valhalla, NY 10595, or at piero_anversa{at}nymc.edu.
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Fernandez-Aviles, F., San Roman, J. A., Garcia-Frade, J., Fernandez, M. E., Penarrubia, M. J., de la Fuente, L., Gomez-Bueno, M., Cantalapiedra, A., Fernandez, J., Gutierrez, O., Sanchez, P. L., Hernandez, C., Sanz, R., Garcia-Sancho, J., Sanchez, A.
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