This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (49)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Pregnancy and Breast Feeding  • Pathology & Laboratory Medicine  • Alert me on articles by topic

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.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Fetal cells in the maternal appendix: a marker of inflammation or fetal tissue repair?
Santos et al.
Hum Reprod 2008;0:den261v1-7.
ABSTRACT | FULL TEXT  

High frequency of fetal cells within a primitive stem cell population in maternal blood
Mikhail et al.
Hum Reprod 2008;23:928-933.
ABSTRACT | FULL TEXT  

Pregnancy Allows the Transfer and Differentiation of Fetal Lymphoid Progenitors into Functional T and B Cells in Mothers
Khosrotehrani et al.
J. Immunol. 2008;180:889-897.
ABSTRACT | FULL TEXT  

Tissue chimerism in systemic lupus erythematosus is related to injury
Kremer Hovinga et al.
Ann Rheum Dis 2007;66:1568-1573.
ABSTRACT | FULL TEXT  

Fetal Microchimerism in Women with Breast Cancer
Gadi and Nelson
Cancer Res. 2007;67:9035-9038.
ABSTRACT | FULL TEXT  

Local and Circulating Microchimerism Is Associated with Hypersensitivity Pneumonitis
Bustos et al.
Am. J. Respir. Crit. Care Med. 2007;176:90-95.
ABSTRACT | FULL TEXT  

Fetomaternal Cell Trafficking and the Stem Cell Debate: Gender Matters
Bianchi and Fisk
JAMA 2007;297:1489-1491.
FULL TEXT  

Fetal cells participate over time in the response to specific types of murine maternal hepatic injury
Khosrotehrani et al.
Hum Reprod 2007;22:654-661.
ABSTRACT | FULL TEXT  

Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells
Nguyen Huu et al.
Proc. Natl. Acad. Sci. USA 2007;104:1871-1876.
ABSTRACT | FULL TEXT  

Chimerism in systemic lupus erythematosus--three hypotheses
Kremer Hovinga et al.
Rheumatology (Oxford) 2007;46:200-208.
ABSTRACT | FULL TEXT  

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet beta cell microchimerism
Nelson et al.
Proc. Natl. Acad. Sci. USA 2007;104:1637-1642.
ABSTRACT | FULL TEXT  

Sex differences in autoimmune disease
Lockshin
Lupus 2006;15:753-756.
ABSTRACT  

Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?
Stevens
Lupus 2006;15:820-826.
ABSTRACT  

Complement-Dependent Control of Teratoma Formation by Embryonic Stem Cells
Koch et al.
J. Immunol. 2006;177:4803-4809.
ABSTRACT | FULL TEXT  

Breast milk: an unappreciated source of stem cells.
McGregor and Rogo
J Hum Lact 2006;22:270-271.
 

A natural stem cell therapy? How novel findings and biotechnology clarify the ethics of stem cell research.
Patel
J. Med. Ethics 2006;32:235-239.
ABSTRACT | FULL TEXT  

Parity and the Risk of Autoimmune Thyroid Disease: A Community-Based Study
Walsh et al.
J. Clin. Endocrinol. Metab. 2005;90:5309-5312.
ABSTRACT | FULL TEXT  

Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse
Khosrotehrani and Bianchi
J. Cell Sci. 2005;118:1559-1563.
ABSTRACT | FULL TEXT  

Skin Carcinoma Arising From Donor Cells in a Kidney Transplant Recipient
Aractingi et al.
Cancer Res. 2005;65:1755-1760.
ABSTRACT | FULL TEXT  

Thyroid Fetal Male Microchimerisms in Mothers with Thyroid Disorders: Presence of Y-Chromosomal Immunofluorescence in Thyroid-Infiltrating Lymphocytes Is More Prevalent in Hashimoto's Thyroiditis and Graves' Disease Than in Follicular Adenomas
Renne et al.
J. Clin. Endocrinol. Metab. 2004;89:5810-5814.
ABSTRACT | FULL TEXT  

Fetal Microchimeric Cells and Breast Cancer
Frank
JAMA 2004;292:1552-1552.
FULL TEXT  

Stem Cell Transfer and the Uterus: The Egg Teaches the Chicken
Polan and Yao
JAMA 2004;292:104-105.
FULL TEXT