Fetomaternal microchimerism

Abstract

The transfer of fetal cells into mothers during pregnancy and their organ specific integration is a well recognized phenomenon in placental vertebrates. Recently, it has been reported that some fetal cells found in the mothers have progenitor cell-like features such as multilineage differentiation potential and as a consequence they were termed pregnancy associated progenitor cells (PAPC). The multilineage differentiation potential suggested some level of cellular plasticity, which these cells share with other stem or progenitor cells. In this context, we have shown that PAPCs indeed express neural stem cell and markers for developing neurons in the brain and that PAPCs morphologically mature into neurons over time. The stem/progenitor properties of PAPCs raises the hope that they might be valuable for studying the functional integration of foreign cells into preexisting tissues and organs, for example in cellular therapies. The functional integration of transplanted cells and their connectivity to the host circuitry is still a major bottleneck in cellular therapies particularly for the brain. The animal models of fetomaternal microchimerism might provide valuable insights into the mechanism how cells survive, migrate, integrate and differentiate in a foreign environment of a host. This review discusses some of the recent findings in the field of fetomaternal microchimerism. It also tries to identify some major gaps of knowledge and raises some questions resulting from the recent advances. Studying fetomaternal microchimerism and the properties of PAPCs in greater detail might pave the way to advance cell based regenerative medicine as well as transplantation medicine.

Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage

“…The progress of knowledge allowed disproving some of the theories regarding the placental barrier, insufficient maturity of fetal antigens or a weakening of the immune response during pregnancy. Nowadays it is known that during pregnancy the direct contact occurs between the fetal and maternal cells, and fully mature antigens of the major histocompatibility complex present on placental or fetal cells penetrate into the maternal circulation, where they have the potential ability to induce a strong immune response leading to rejection of the foreign allogeneic tissue [ 15 , 16 ]. Furthermore, the immune system in pregnancy is not in a state of inertia, as recognition of fetal antigens by maternal immune competent cells leads to the development of the cascade of immunological events [ 17 ].…”

Transfer and Integration of Breast Milk Stem Cells to the Brain of Suckling Pups

“…The latter has been known for long and shown to involve many organ and tissues from the bone marrow to the heart 28 , 29 , 41 though no report on the brain involvement has been published so far, which adds to the novelty of our findings. Fetal cells can also pass through the placenta and lead to fetal microchimerism 42 , which is out of scope of this paper.…”

Cell fusion in the brain: two cells forward, one cell back

“…The novel observation of this study was that two Purkinje cells were found with more than a diploid sex chromosome composition (both a XXY and XXX phenotype was found), raising the tentative prospect that BM-derived cells donate genetic material to Purkinje cells through fusion events between these two distinct cell types. (Note: when interpreting the presence of Y chromosome-positive cells in the females after male BM transplantation, the possible confounding factor regarding feto-maternal chimerism and the transfer of cells from the male foetus to its mother must be considered [ 41 ]. The child-bearing status of the female subjects was not reported in these studies, therefore the observation of Y chromosomes in the brain being a result of feto-maternal chimerism cannot be ruled out.)…”