Implications of fetal stem cell trafficking in pregnancy

Fetal stem cells can be isolated from fetal blood and bone marrow as well as other fetal tissues. Fetal blood is both a source of haemopoietic stem cells, which proliferate more rapidly than those in cord blood or adult bone marrow, and a source of non-haemopoietic mesenchymal stem cells, which support haemopoiesis and can also differentiate along multiple lineages. Although the placenta was traditionally seen as a barrier separating the genetically distinct mother and fetus, it is now recognised that fetal cells pass into the maternal circulation throughout normal pregnancy. This cell traffic may help establish maternal tolerance to the fetal allograft. The principal mechanism is fetomaternal haemorrhage, as evidenced by the variety of fetal cell types, including stem cells, identified in maternal blood.

Isolation of fetal cells from the maternal circulation in pregnancy has been investigated as an alternative to existing methods of genetic prenatal diagnosis. Fetal stem cells have considerable potential for non-invasive prenatal testing, as they differ in phenotype from other cells circulating in the adult and can be amplified into large numbers for analysis after enrichment from maternal blood. Stem cells isolated from the fetus may be transplanted in utero to treat genetic disease and also show promise as targets for gene therapy, which could be applied to diseases such as osteogenesis imperfecta or muscular dystrophies.

The destination of fetal stem cells after trafficking across the placenta is the subject of much debate. While these cells may persist in blood in undetectable amounts, it is more likely that stem cells engraft in maternal tissues and persist for years after pregnancy, as has been demonstrated by finding fetal mesenchymal stem cells in post-reproductive tissues. Fetal microchimerism, which refers to low levels of fetal cells harboured by the mother, has been associated with the development of autoimmune disease in the mother and with repair of damaged tissues. However, fetal stem cells in maternal tissues could also act as a long-term reservoir of stem cells and may even explain why women live longer than men and why pregnancy protects against susceptibility to some diseases. Cellular trafficking in pregnancy has far reaching biological consequences.