1444 Harnessing the potential of fetal microchimeric cells to improve maternal wound healing

Fetal microchimeric cells (FMC) are fetal progenitor cells transferred to the mothers during pregnancy that niche into bone marrow, where they persist during the mother’s lifetime. Upon skin injury during pregnancy, FMC are recruited to maternal wounds where they participate to wound healing. First, we evaluated FMC healing capacities in both normal and delayed wound healing during post-partum. We found that skin healing was improved in post-partum mice compared with virgin mice, and was associated with increased proliferation and angiogenesis rates, in parallel with fetal cell recruitment to the wounds. Next, we performed whole-mount immunostainings and 3D microscopy of bone marrow to visualize FMC within their niche in wounded post-partum mice. We confirmed that FMC display Sca-1-positive hematopoietic stem cell profiles, but also profiles of differentiated myeloid cells expressing CD45 and CD11b, or endothelial cells expressing CD31. In parallel, we are performing single-cell RNA sequencing of FMC isolated from bone marrow and skin in wounded and unwounded post-partum mice.. Finally, in order to better understand the possible fates of FMC and the pathways favoring specific differentiations, we sorted different bone marrow progenitor populations from wounded post-partum females and cultured them at low density in methylcellulose. About 2% of the colonies obtained after 14 days of culture of monocyte dendritic cell progenitors and granulocyte monocyte progenitors were of fetal origin. The different possible fates and the underlying mechanisms of differentiation are under investigation. Taken together, these results confirm the plasticity of FMC and their role in wound healing during post-partum. By characterizing the signaling pathways that control FMC mobilization and differentiation, we aim to exploit their potential to use them as therapeutic tools to treat delayed wound healing in parous women.