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Kiarash Khosrotehrani, MD; Kirby L. Johnson, PhD; Dong Hyun Cha, MD; Robert N. Salomon, MD; Diana W. Bianchi, MD

JAMA. 2004;292:75-80.

Context  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.

Design, Setting, and Patients  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.

Main Outcome Measure  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 ( = 0.72).

Conclusion  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.

Author Affiliations: Departments of Pediatrics and Obstetrics and Gynecology (Drs Khosrotehrani, Johnson, Cha, and Bianchi), and Department of Pathology (Dr Salomon), Tufts-New England Medical Center, Boston, Mass.

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