Endothelial stem cells (ESCs) are one of three types of stem cells found in bone marrow. They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types. ESCs have the characteristic properties of a stem cell: self-renewal and differentiation. These parent stem cells, ESCs, give rise to progenitor cells, which are intermediate stem cells that lose potency. Progenitor stem cells are committed to differentiating along a particular cell developmental pathway. ESCs will eventually produce endothelial cells (ECs), which create the thin-walled endothelium that lines the inner surface of blood vessels and lymphatic vessels.
ECs were first thought to arise from extraembryonic tissues because blood vessels were observed in the avian and mammalian embryos. However, after histological analysis, it was seen that ECs were in the embryo. This meant that blood vessels come from an intraembryonic source, the mesoderm.
Self-renewal and differentiation
Stem cells have the unique ability make identical copies of themselves. This property maintains unspecialized and undifferentiated cells within the body. Differentiation is the process by which a cell becomes more specialized. For stem cells, this usually occurs through several stages, where a cell proliferates giving rise to daughter cells that are further specialized. For example, an endothelial progenitor cell (EPC) is more specialized than an ESC, and an EC is more specialized than an EPC. The further specialized a cell is, the more differentiated it is and as a result it is considered to be more committed to a certain cellular lineage.
Blood vessel formation
Blood vessels are made of a thin layer of ECs. As part of the circulatory system, blood vessels play a critical role in transporting blood throughout the body. Consequently, ECs have unique functions such as fluid filtration, homeostasis and hormone trafficking. ECs are the most differentiated form of an ESC. Formation of new blood vessels occurs by two different processes: vasculogenesis and angiogenesis. The former requires differentiation of endothelial cells from hemangioblasts and then the further organization into a primary capillary network. The latter occurs when new vessels are built from preexisting blood vessels.
The vascular system is made up of two parts: 1) Blood vasculature 2) Lymphatic vessels
Both parts consist of ECs that show differential expression of various genes. A study showed that ectopic expression of Prox-1 in blood vascular ECs (BECs) induced one-third of LEC specific gene expression. Prox-1is a homeobox transcription factor found in lymphatic ECs (LECs). For example, specific mRNAs such as VEGFR-3 and p57Kip2 were expressed by the BEC that was induced to express Prox-1.
Lymphatic-specific vascular endothelial growth factors VEGF-C and VEGF-D function as ligands for the vascular endothelial growth factor receptor 3 (VEGFR-3). The ligand-receptor interaction is essential for normal development of lymphatic tissues.
Tal1 gene is specifically found in the vascular endothelium and developing brain. This gene encodes the basic helix-loop-helix structure and functions as a transcription factor. Embryos lacking Tal1 fail to develop past embryonic day 9.5. However, the study found that Tal1 is actually required for vascular remodeling of the capillary network, rather than early endothelial development itself.
Fetal liver kinase-1 (Flk-1) is a cell surface receptor protein that is commonly used as a marker for ESCs and EPCs.
CD34 is another marker that can be found on the surface of ESCs and EPCs. It is characteristic of hematopoietic stem cells, as well as muscle stem cells.