Microchimeric fetal cells play a role in maternal wound healing after pregnancy
Uzma Mahmood and Keelin O’Donoghue
Fetal cells persist in mothers for decades after delivery: in a phenomenon called fetal microchimerism. While persistent fetal cells were first implicated in autoimmune disease, parallel studies in animal and human pregnancy now suggest that microchimeric fetal cells play a role in the response to tissue injury. The aim of this study was to investigate the impact of fetal microchimeric cells in the adult wound, using caesarean section (CS) as a model of wound healing in pregnancy. XY-FISH (fluorescence in situ hybridization) and immunostaining was used in multiple tissue sections from CS skin biopsies from 70 women, to locate, quantitate and characterize microchimeric male presumed-fetal cells. Y-FISH and Nested PCR was used to confirm XY-FISH results. XY-FISH demonstrated the presence of isolated 0–9 male fetal cells per section in the epidermis of the healed CS scars from only those women who had their first male child by CS. Both Y-FISH and Y-PCR confirmed the presence of fetal cells in CS scars. Combined FISH and immunostaining showed all male fetal cells present were keratinocytes, as they expressed cytokeratin, and were almost exclusively located in epidermis. Microchimeric fetal cells also expressed Collagen I, III, and TGF-β3 in healed maternal scars. Identification of male–presumed fetal cells in healed maternal CS scars after pregnancy suggests that, possibly in response to signals produced by maternal skin injury at CS, fetal cells migrate to the site of damage to become involved in maternal tissue repair, or proliferate locally.
Analysis of maternal microchimerism in rhesus monkeys (Macaca mulatta) using real-time quantitative PCR amplification of MHC polymorphisms
Sonia Bakkour, Chris AR Baker, Alice F Tarantal, Li Wen, Michael P Busch, Tzong-Hae Lee and Joseph M McCune
Although pregnancy-associated microchimerism is known to exist in humans, its clinical significance remains unclear. Fetal microchimerism has been documented in rhesus monkeys, but the trafficking and persistence of maternal cells in the monkey fetus and infant have not been fully explored. To investigate the frequency of maternal microchimerism in the rhesus monkey (Macaca mulatta), a real-time polymerase chain reaction (PCR) strategy was developed and validated to target polymorphic major histocompatibility complex (MHC) gene sequences. Informative PCR assays were identified for 19 of 25 dams and their respective offspring. Analyses were performed on tissues (thymus, liver, spleen, lymph nodes, and bone marrow) and peripheral blood mononuclear cells (PBMCs) collected prenatally and postnatally in a subset of animals. Seven of 19 monkeys had detectable maternal microchimerism in at least one compartment (range: 0.001–1.9% chimeric cells). In tissues, maternal microchimerism was found in 2 of 7 fetuses and 3 of 12 juveniles (1–1.5 years of age), and most of the animals that were positive had microchimeric cells in more than one tissue. Maternal microchimerism was detected in PBMCs from all (4 of 4) fetuses. These observations suggest that maternal microchimerism occurs in the rhesus monkey fetus and can be detected in tissues in a subset of offspring after birth.
Maternal microchimerism in biliary atresia: Are maternal cells effector cells, targets, or just bystanders?
The etiology of biliary atresia (BA) is unknown; however, the liver histology is similar to that observed in immune-mediated hepatic disorders. Liver fibrosis in BA progresses even after bile drainage has been achieved by the Kasai operation. Maternal microchimerism has been purported to play a part in the pathogenesis of BA as well as certain autoimmune diseases. However, the role of maternal cells has not yet been determined in BA. Specifically, it is unknown whether these maternal cells function as maternal effector T lymphocytes, or targets or bystanders. We currently hypothesize that the first hit is due to GvHD interaction by engrafted maternal effector T lymphocytes. Furthermore, we suggest that the secondary effects that are manifested by progressive cirrhosis are caused either by maternal chimeric effector T lymphocytes (e.g., GvHD interaction) or targets (e.g., HvGD interaction). Based on our hypothesis, mixed lymphocyte reactions between patients and their mothers might shed light on the etiopathogenesis and prognostic indicators.