Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts.
BACKGROUND
Mesenchymal precursor cells are able to respond to tissue signals and differentiate into a phenotype characteristic of mature cells of that tissue. We sought to investigate whether adult human cardiomyocytes can be derived from recipient precursor cells in sex-mismatched cardiac allografts.


METHODS
We studied four male patients who received hearts from female donors, and four female patients who received an allograft from a male donor. Four sex-matched transplant patients, two of each sex served as controls. Combined fluorescence in situ hybridization with probes specific for X- and Y-chromosomes and immunohistochemistry with alpha-actin was used to identify cardiac muscle cells 4 and 12 months after transplantation. Slides were examined with a fluorescence microscope to detect the presence of male cells with one X and one Y signal in the nucleus, and female cells containing two X signals.


RESULTS
Mature cardiomyocytes from the host (1-2%) were found in five endomyocardial biopsy specimens at 4 months, and in three specimens at 12 months. In addition, recipient cells negative for cytoplasmic alpha-actin were also identified (1-21% per slide). The number of infiltrating recipient cells was not associated with the degree of rejection of the sample or with the number of prior rejection episodes. Echocardiographic evaluation showed no improvement in cardiac performance in hearts from patients with more than 10% chimeric recipient cells.


CONCLUSIONS
Our data confirm the existence of mature cardiomyocytes derived from host cells, likely mesenchymal precursors, in the adult cardiac allograft in vivo.
Bayes-Genis
Antoni
A
Servei de Cardiologia, Hospital de la Santa Creu i Sant Pau, C/San Antonio Ma Claret 167, 08025, Barcelona, Spain.
Salido
Marta
M
Solé Ristol
Francesc
F
Puig
Mireia
M
Brossa
Vicens
V
Campreciós
Marta
M
Corominas
Josep M
JM
Mariñoso
Ma Luísa
ML
Baró
Teresa
T
Vela
Ma Carmen
MC
Serrano
Sergi
S
Padró
Josep M
JM
Bayes de Luna
Antoni
A
Cinca
Juan
J
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000473:pathology* / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008648:Mesoderm / Q000166:cytology; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000166:cytology*; D012737:Sex Factors; D013234:Stem Cells / Q000166:cytology; D018183:Transplantation Chimera / Q000033:anatomy & histology* / Q000502:physiology; D016277:Ventricular Function, Left
D000199:Actins