Transfer of Fetal Cells with Multilineage Potential to Maternal Tissue

Abstract

Recent studies report finding male cells, presumably of fetal origin, in up to half of healthy women who have had male pregnancies. Women with some autoimmune disorders have increased numbers of fetal microchimeric cells,as do some women with nonautoimmune disorders such as cervical cancer and hepatitis C. The investigators examined the hypothesis that, rather than causing maternal disease, fetal cells respond to injury by developing multilineage capacity in maternal organs. Male cells were sought in 10 women having male offspring who were known to have high numbers of microchimeric cells and in 11 control women without a prior male pregnancy. Male cells were identified by fluorescence in situ hybridization using X and Y chromosome-specific probes. Immunochemical studies utilized anticytokeratin as a marker of epithelial cells; anti-CD45 as a leukocyte marker; and hepar-1 as a hepatocyte marker. A total of 701 male (XY+) microchimeric cells were identified, reflecting a mean number of 227 per million maternal cells. In maternal samples of thyroid, cervix, intestine, and gallbladder, from 14% to 60% of XY+ cells expressed cytokeratin. In hematopoietic tissues such as lymph nodes and spleen, 90% of XY+ cells expressed CD45. In a single liver sample, 4% of XY+ cells expressed hepar-1. Independent observers provided concordant results when evaluating histological and immunochemical evidence of differentiation. Fetal cells present in a wide range of maternal tissues have characteristics not only of hematopoietic cells, but also epithelial and liver cells. Fetal cells transferred during pregnancy have multilineage capacity, either through cell fusion or trans-differentiation.