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    Role of fetal microchimeric cells in maternal healing

    Maria Sbeih

     

    Friday 26th February 2021 2 pm

    Institut Cochin

    22 rue Méchain Paris 75014

    Rosalind Franklin room, second floor





    Supervisor: Sélim Aractingi

    Team: Biologie Cutanée

    Department : Développement, Reproduction, Cancer (DRC)

    Abstract:

    During gestation, fetal cells are transferred to the maternal circulation and persist in the mother for decades after delivery, by homing to the maternal bone marrow. These Fetal Microchimeric Cells (FMCs) include various types of progenitors that can migrate to an injured maternal tissue, including the skin, and participate in its repair. During my thesis, I have worked on the effect of FMCs recruited in cutaneous wounds of pregnant and post-pregnant mice. In both conditions, FMCs improved healing though stimulation of wound angiogenesis and cell proliferation. When studying their transcriptome during and after gestation, several stemness markers appeared to be expressed. We then described a specific signaling pathway regulating the traffic of an FMC subpopulation: the CCR2/CCL2 pathway. This subpopulation displays a CCR2+ myeloid progenitor phenotype and is recruited in the wounds in response to CCL2 secreted by maternal monocytes. Thus, a subcutaneous injection of CCL2 increases fetal cell recruitment and improves wound healing in pregnant and post-pregnant mice. This is due to the differentiation of FMCs into blood vessels and to their secretion of specific pro-angiogenic factors. On the other hand, intracerebral injection of CCL2 improves brain repair after induction of excitotoxic lesions in post-pregnant mice. These results pave the way for a “natural stem cell therapy” based on the stimulation of a certain signaling pathway to selectively recruit fetal progenitors in a maternal tissue injury. This therapy offers several advantages over current stem cell therapies and shows promising advances in the treatment of deficient maternal tissue repair.