Placental cells increase angiogenesis during skin wound healing

During pregnancy, fetal progenitor cells such as hematopoietic or mesenchymal stem cells, enter maternal circulation. We and others have shown that fetal cells may adopt various phenotypes in maternal injured tissues suggesting multipotent capacities. More recently, we reported that fetal endothelial progenitor cells could home to maternal sites of skin inflammation and formed new blood vessels. Skin wound healing is a process involving different stem cell populations. In this project, we asked whether fetal cells isolated from early placentas could improve skin wounds. Single cell suspension of 10-12 day old placentas from EGFP+ fetuses were obtained and injected subcutaneously in C57Bl/6 female mice that had a surgical wound. For each placenta, the caudal half of the corresponding fetus was as well injected as a control in a separate mouse. Similarly, we injected human first trimester placental cells in wounds performed on nude mice. Wounds that received placental cells in situ were evaluated for the presence and the phenotype of the injected cells and the number of CD31+ blood vessels under the wound and in the surrounding area. Fetal EGFP+ cells could be visualized in fibrotic skin wounds after injection. There was a significant increase in the number of blood vessels found in wounds receiving placentas (n=9) when compared to wounds injected with the fetal caudal half (n=9) or the vehicle alone (n=5) (11.4 versus 9.5 et 9.1 respectively, p= 0,02). Wounds injected with human placental cells displayed human cells that could proliferate (Ki67+), express vimentin or CD34 and were organized as blood vessels. In conclusion, we observed an increase in the number of blood vessels after injection of placental cells. This may reflect the activity of endothelial progenitor cells or be the consequence of angiogenic factors released by placental cells