Abnormal Placental Stem Cells And Their Role In Human Pregnancy Pathologies

Summary This project will explore the molecular mechanisms by which extracellular vesicles derived from normal and pathological placental mesenchymal stem cells, modulate endothelial cell function.

Project Details

The therapeutic potential of human placental mesenchymal stem cells is the subject of intense investigation in the field of regenerative medicine. However, the function of stem cells in the placenta, and their contribution to human pregnancy pathologies, is poorly understood. In many organs, including the placenta, mesenchymal stem cells are found in very close proximity to endothelial cells that comprise the vessel walls, and the two cell types interact. Mesenchymal stem cells secrete nano-sized extracellular vesicles that are are taken up by endothelial cells and they modulate endothelial function. Correct function of endothelial blood vessels is crucial in early placental development since placental pathologies (e.g. preeclampsia, fetal growth restriction, gestational diabetes) feature abnormal blood vessel development in their aetiology.
In this project we will explore the molecular mechanisms by which extracellular vesicles derived from normal and pathological placental mesenchymal stem cells, modulate endothelial cell function.

The work will involve the preparation and characterisation of stem cells and extracellular vesicles, which includes cell culturing, flow cytometry, differentiation assays, ultracentrifugation, electron microscopy, Nanosight analysis and Western analysis. The effect of extracellular vesicles on endothelial cells will be determined by an array of functional assays including xCELLigence assays (for proliferation and migration), oxidative stress assays and endothelial cell tube formation assays.