326 Healing properties of fetal cells beyond pregnancy

Abstract

Chronic leg ulcers are a severe and disabling condition that still constitute a significant global health issue and for which there has been no therapeutic innovation during the last decades. Sickle cell disease (SCD) leads to prolonged and refractory human ulcers. Fetal microchimeric cells (FMCs) are transferred to mothers during pregnancy and niche into maternal bone marrow where they persist for decades. We have shown that during pregnancy, they are recruited to maternal wounds and improve wound healing. In this work, we sought to evaluate whether the healing capacities of FMCs were sustained after pregnancy in both normal and delayed wound healing in a sickle cell mice model (SAD). We found that healing kinetics were similarly improved in pregnant and post-partum wild-type mice, through increased cell proliferation and angiogenesis. Post-partum SAD mice also showed an accelerated healing compared to virgin mice, associated with the recruitment of FMCs to the wound and increased neovascularization. We then analyzed clinical parameters in both nulliparous or ever-parous women suffering from sickle cell disease and leg ulcers. The analysis of multiple parameters such as number of leg ulcers episodes, hospital admission, infection rate, pain severity and skin graft requirements showed an overall better prognosis in ever-parous SCD women as compared to nulliparous women. Taken together, these results indicate that healing capacities of FMCs are maintained long after delivery. This supports a potential therapeutic use of FMCs to treat delayed wound healing in post-partum women.