University College London (UCL) scientists report that a unique source of stem cells in blood helps to build blood vessels in the growing embryo. They say their study (“Erythro-myeloid progenitors contribute endothelial cells to blood vessels”) in Nature changes scientific understanding of how blood vessels are made and brings researchers  one step closer to using stem cells to grow new blood vessels and repair damaged ones.


“The earliest blood vessels in mammalian embryos are formed when endothelial cells differentiate from angioblasts and coalesce into tubular networks. Thereafter, the endothelium is thought to expand solely by proliferation of pre-existing endothelial cells. Here we show that a complementary source of endothelial cells is recruited into pre-existing vasculature after differentiation from the earliest precursors of erythrocytes, megakaryocytes, and macrophages, the erythro-myeloid progenitors (EMPs) that are born in the yolk sac. A first wave of EMPs contributes endothelial cells to the yolk sac endothelium, and a second wave of EMPs colonizes the embryo and contributes endothelial cells to intraembryonic endothelium in multiple organs, where they persist into adulthood,” write the investigators.


“By demonstrating that EMPs constitute a hitherto unrecognized source of endothelial cells, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing endothelial cells and the incorporation of endothelial cells derived from hematopoietic precursors.”


Growing and repairing blood vessels is a major goal in treating heart and circulatory diseases, where vessels become damaged (e.g., coronary heart disease and peripheral arterial disease).


Until now scientists thought that new blood vessels in the embryo only grew when existing endothelial cells divided. The new research shows that stem cells in the bloodstream can develop into endothelial cells and add to the vessel wall. Specifically, the study provides important new evidence that endothelial progenitor cells exist in the bloodstream of developing embryos. A next step will be to determine whether these cells can add to the lining of blood vessels throughout life, and tracking them down in humans.


The researchers used fluorescent tags to follow the fate of the EMPs. These cells were already known to develop into red blood cells and certain types of immune cells. EMP stem cells grown in a dish developed into endothelial cells as well as red blood cells and immune cells. The EMP stem cells also developed into endothelial cells in mice that were naturally growing in their mother's womb, and they continued to line blood vessels into adulthood.


Methods need to be developed in order to track these elusive cells down in humans. More research is also needed to determine if the endothelial cells that come from EMPs have their own unique function and just how they can be used in regenerative medicine.


According to Christiana Ruhrberg, Ph.D., professor of neuronal and vascular development, at the UCL Institute of Ophthalmology and senior author of the study,  “Until now, scientists thought EMPs only formed red blood and immune system cells in the fetus. To find that they also generate endothelial cells for growing new blood vessels in the fetus was unexpected and is hugely exciting.”



“Using stem cells to treat patients with heart and circulatory disease has huge potential. But taking positive findings from the lab to patients has often been very challenging,” adds Metin Avkiran, Ph.D., DSc, associate medical director at the British Heart Foundation.


“These scientists have looked at how blood vessels develop in the embryo, and their findings have shed important new light on our understanding of the origin of growing blood vessels.


“Getting these fundamentals right is essential for finding stem cell treatments which will work in patients. These findings could pave the way to new discoveries in regenerative medicine and allow scientists in the future to grow new blood vessels and repair those that are damaged in many forms of heart and circulatory disease.”








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