Clinical implications of maternal-fetal cellular trafficking
Introduction
Maternal-fetal cellular trafficking (MFCT) is the bidirectional passage of cells between a mother and her fetus resulting in long-lived maternal cells in the fetus1 and fetal cells in the mother.2 The diagnostic potential of detecting fetal chromosomal abnormalities in maternal serum has led to extensive study of fetal-to-maternal cell trafficking (which results in fetal microchimerism, FMc, in mothers). Although the actual function of this trafficking is unknown, it is thought that fetal cells may trigger autoimmune disease3, 4, 5, 6 or play a regenerative role in maternal tissues after injury.7, 8 Similarly, maternal-to-fetal cellular trafficking (which results in maternal microchimerism (MMc), in fetuses) may have implications for the pathogenesis of autoimmune and other diseases in children. MMc may also lead to the development of long-lived tolerance to maternal antigens. In this review, we will summarize the potential role of FMc and MMc in maternal and pediatric disorders and explore the role of MMc in the development of maternal-fetal tolerance.
Section snippets
Fetal microchimerism
One of the earliest reports of FMc was from Georg Schmorl in the late 1800's, who identified placental trophoblast cells of fetal origin in mothers who died of eclampsia.9 Since these early findings, multiple reports have documented the presence of fetal cells and cell-free fetal DNA in maternal blood during normal pregnancy.10, 11, 12 The detection of cell-free fetal DNA, in particular, has been a major focus in the study of FMc given the obvious clinical application of detecting fetal
Maternal microchimerism
The first description of MMc was in 1963, when maternal leukocytes were identified in the cord blood of newborn infants.21 With the development of more sensitive PCR based assays, investigators have since identified long-lived maternal cells in healthy adult patients.1 More recent data has demonstrated the diverse tissue distribution of maternal cells, with reports of MMc in the blood, brain, heart, intestine, lungs, liver, muscle, pancreas, skin, and spleen.22, 23, 24, 25, 26, 27, 28, 29, 30,
Alterations in microchimerism after fetal intervention
The trafficking of fetal cells or cell-free DNA into the mother has been studied after fetal intervention. Fetal intervention may lead to changes in the placenta or fetal membranes, with resultant alterations in trafficking. Laser ablation of inter-twin vessels for twin–twin transfusion syndrome (TTTS) has been associated with increased levels of circulating fetal DNA in maternal circulation for up to 48 h after the procedure. In this study, elevated levels of fetal DNA at 24 h was associated
Conclusions and future directions
The role of MFCT in maternal and fetal health remains a fascinating yet unanswered question. Insights into this biological phenomenon will prove useful for understanding the origins of autoimmune conditions, transplantation tolerance, and maternal-fetal tolerance during pregnancy. Progress in our understanding of the clinical implications of MFCT will rely on our ability to understand the mechanism leading to trafficking as well as the mechanism by which trafficked cells contribute to disease.
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