Contribution of fetal microchimeric cells to maternal wound healing in sickle cell ulcers

Abstract

Leg ulcers are a major complication of sickle cell disease (SCD) that can cause severe complications. They are particularly challenging to treat and therapeutic innovation is needed. We previously showed that SCD ulcers display a delayed wound healing due to decreased angiogenesis. During pregnancy, fetal microchimeric cells (FMC) transferred to the mothers are recruited to maternal wounds and improve angiogenesis. After delivery, FMC persist in maternal bone marrow for decades. Here, we questioned whether fetal cells could also improve SCD ulcers in the post-partum setting. We found that skin healing was similarly improved in post-partum mice and in pregnant mice, through increased proliferation and angiogenesis. In a SCD mouse model that recapitulates SCD refractory ulcers, we showed that post-partum SCD mice healed more quickly as compared to virgin ones. This was associated with the recruitment of fetal cells in maternal wounds where they harbored markers of leukocytes and endothelial cells. In a retrospective cohort of SCD patients, we demonstrated using several parameters that ever parous SCD women had a decreased burden related to leg ulcers compared to nulliparous women. Taken together, these results indicate that healing capacities of FMC are maintained long after delivery and may be targeted to promote wound healing in post-partum SCD patients.