Transfer of fetal cells with multilineage potential to maternal tissue.
BACKGROUND
During pregnancy, fetal CD34+ cells enter the maternal circulation, persist for decades, and create a state of physiologic microchimerism. Many studies have confirmed the residual presence of fetal cells in maternal blood and tissues following pregnancy. Fetal cells may respond to maternal injury by developing multilineage capacity in maternal organs.


OBJECTIVE
To verify that fetal microchimeric cells express markers of epithelial, leukocyte, and hepatocyte differentiation within maternal organs.


METHODS
Archived paraffin-embedded tissue section specimens from 10 women who had male offspring and were previously found to have high numbers of microchimeric cells, and 11 control women who had no prior male pregnancies. Male cells were identified by fluorescence in situ hybridization, using X and Y chromosome-specific probes, followed by histologic and immunochemical studies using anticytokeratin (AE1/AE3) as a marker of epithelial cells, anti-CD45 as a leukocyte marker, and heppar-1 as a hepatocyte marker.


METHODS
Percentage of microchimeric cells expressing nonhematopoietic markers.


RESULTS
A total of 701 male (XY+) microchimeric cells were identified (mean [SD], 227 [128] XY+ cells per million maternal cells). In maternal epithelial tissues (thyroid, cervix, intestine, and gallbladder), 14% to 60% of XY+ cells expressed cytokeratin. Conversely, in hematopoietic tissues, such as lymph nodes and spleen, 90% of XY+ cells expressed CD45. In 1 liver sample, 4% of XY+ cells expressed heppar-1. Histologic and immunochemical evidence of differentiation, as assessed by independent observers, was highly concordant (kappa = 0.72).


CONCLUSIONS
The detection of microchimeric male cells, bearing epithelial, leukocyte, or hepatocyte markers, in a variety of maternal tissue specimens suggests the presence of fetal cells that may have multilineage capacity.
Khosrotehrani
Kiarash
K
Department of Pediatrics, Tufts-New England Medical Center, Boston, Mass 02111, USA.
Johnson
Kirby L
KL
Cha
Dong Hyun
DH
Salomon
Robert N
RN
Bianchi
Diana W
DW
D000328:Adult; D000368:Aged; D001457:Anion Exchange Protein 1, Erythrocyte; D002454:Cell Differentiation; D002678:Chimera / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005333:Fetus / Q000166:cytology*; D005704:Gallbladder / Q000166:cytology; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007422:Intestines / Q000166:cytology; D017493:Leukocyte Common Antigens; D007962:Leukocytes / Q000166:cytology*; D008099:Liver / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D011247:Pregnancy; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D013961:Thyroid Gland / Q000166:cytology
D001457:Anion Exchange Protein 1, Erythrocyte; D017493:Leukocyte Common Antigens