Fetal-Maternal Microchimerism: Basis for a Potential New Therapy for Malignancy?.

Fetal-maternal microchimerism [MC] occurs during gestation or delivery, as cells traffic from the fetal circulation to the maternal circulation (and vice versa) via the placenta, and persist for decades post-partum. The reported incidence of MC is 33% in normal parous women. To explore the incidence and extent of MC among normal females and cancer patients for potential therapy, we obtained blood samples from 162 normal parous women, and 21 parous cancer patients. 30 non-parous women served as controls. The presence of male DNA was detected using two rounds of PCR with nested sets of primers specific for the Y chromosome. The sensitivity of the assay was validated at 1 male cell per 1 million female cells using DNA prepared from serial dilutions of (male) KG-1 cells in (female) K562 cells. The observed frequency of MC was dependent on the amount of DNA assayed: with 1 ug DNA [~300,000 genomes] per test, the frequency of MC was 18%. At 5 ug DNA [1.5 million genomes], this rose to 46%, and at ≥ 25 ug DNA [7.5 million genomes], 66% of normal parous women had MC. Among parous cancer patients, MC was present at 20% with 5 ug DNA, rose to 76% when ≥ 25 ug DNA or more was tested. The lower frequency of MC among cancer patients at 5 ug DNA may reflect the effects of prior chemotherapy. 2 out the 30 normal non-parous donors were chimeric; this number did not increase when more DNA was assayed. The reason for the MC among non-parous subjects is unclear. Our results indicate the MC is much more frequent among parous women than previously reported. Provided that MC confers long-lasting tolerance of fetal tissue antigens, this suggests that son-to-mother cellular therapy may be feasible for treatment of malignancy.