*2.6. Potential Therapeutic Approaches*

Reprogramming of macrophages seems to be an attractive therapeutic strategy. A number of FDA approved approaches involving cellular and gene therapy are now used in clinical practice [112]. Macrophages derived from monocytes can be activated in different ways by varying combinations of external stimuli. The ex vivo reprogramming of macrophages conventionally aims to polarize them towards the anti-inflammatory phenotype in order to make the M2 polarized macrophages confront inflammation in maternal body. The idea of ex vivo reprogramming of autologous macrophages has been developed since the 1980s [113]. By now, the reprogrammed macrophages have been successfully used in a number of therapeutic cases including treatment of cancer, transplantation, and stimulation of regeneration [114–116]. Common approaches for the ex vivo macrophage polarization are stimulation of the cells with cytokine cocktails, genetic manipulation, or using specific low-molecular inhibitors of transcription factors [117,118]. iPS-ML, the macrophage-like myelomonocytic cells generated from the human induced pluripotent stem cells, are also amenable to ex vivo polarization [119]. Injection of the autologous monocyte-derived M2-polarized macrophages at a certain time of gestation (or at the stage of its planning by taking into account the risks of PE) may evolve into a new strategy for PE treatment. Such therapy seems to be promising due to reports about the absence of adverse reactions and long-term side effects after macrophages transplantation in other diseases [120,121]. A possible side effect of the proposed therapy may be the phenomenon of maternal–fetal cellular trafficking—the ability of mother and fetus cells pass the placental barrier [122]. The presence of fetal cells in the maternal circulation is known as fetal microchimerism, while the presence maternal cells in the fetal organism is known as maternal microchimerism. Indeed, in a number of works it was shown that fetuses with severe congenital diaphragmatic hernia have increased levels of maternal microchimerism [122,123]. However, this does not mean that the activated *ex vivo* auto-monocytes will necessarily penetrate the placenta. This question has not been sufficiently investigated.
