Endothelial Colony Forming Cells (ECFCs) Are Significant In Placental Vessel Formation

ECFCs are circulating vasculogenic progenitor cells. Their source and function in the fetoplacental unit are unknown. We hypothesised a role for fetal derived human ECFCs in placental angiogenesis. ECFCs from human umbilical arteries and veins were counted by flow cytometry (7AAD‐/CD31+/CD45‐/KDR+/CD34+), cloned, and lentiviral‐transduced to express EGFP or LacZ for tracking. Angiogenic capacity was investigated by implantation into adult immuno‐deficient (NOD/SCID) mice. ECFCs were transplanted into NOD/SCID fetuses during pregnancy, through sonographic‐guided intra‐cardiac injection. After 3.5 days, localisation and integration of transplanted fetal ECFC were determined. ECFC numbers were higher in human umbilical arteries than veins (4.12x10‐3±4.96x10‐3 vs. 7.40x10‐4±1.44x10‐3%, p<0.01, n=12), suggesting placental uptake. Cloning confirmed a progenitor phenotype and de novo vessel formation of implants demonstrated angiogenic capacity (100%, n=22). Transplanted ECFCs migrated from murine fetuses to placentae, where they formed new vessels (100%, n=27), while HUVEC controls did not (n=4). These findings suggest placental sequestration and vessel formation of fetal ECFCs. This is the first in vivo demonstration of ECFC‐driven endothelium formation in physiological angiogenesis and highlights their role in placentation. Sponsored by The Welcome Trust, UK