The bone marrow contains a special type of progenitor cells that can migrate to the peripheral circulation and develop and grow into endothelial cells. These are thus called endothelial progenitor cells (EPCs).
Main functions of EPCs
The main functions of EPCs are to play a role in endothelial repair and neovascularization of ischemic organs.
Recent studies have shown that these EPCs can induce and regulate the processes of vasculogenesis and angiogenesis in areas with reduced oxygen supply and can also stimulate endothelium formation in injured blood vessels.
Characteristics of EPCs
The EPCs in general are characterized by the expression of 3 markers:-
Vascular endothelial growth factor receptor-2 (VEGF R-2) also called kinase insert domain receptor (KDR) or Flk-1
While differentiating and maturing the EPCs lose CD133 and start to express:–
CD31 or platelet endothelial cell adhesion molecule-1
vascular endothelial cadherin and
von Willebrand factor
Mature endothelial cells thus show VEGFR-2, VE-cadherin, and von Willebrand factor. They also contain NO synthase, and, on stimulation, E-selectin.
Differentiation and maturity of the EPCs
The release of EPCs from the bone marrow into the blood is regulated by a variety of growth factors, enzymes, ligands, and surface receptors. The step usually begins with activation of matrix metalloproteinase-9 that in turn promotes the transformation of membrane-bound Kit ligand to a soluble Kit ligand.
Although the exact mechanism is unclear, the loss of the CD133 and subsequent expression of von Willebrand factor in conjunction with the appearance of other endothelial characteristics seems to be the trigger in stimulating the differentiation of the EPCs into the endothelial cells.
Isolation and culture of EPCs
EPCs are obtained from the bone marrow as well as blood. They are also obtained from fetal liver or umbilical cord blood.
They are usually isolated using adherence culture of total peripheral blood mononuclear cells. Another alternative is the use of magnetic microbeads, coated with anti-CD133 or anti-CD34 antibodies.
Once isolated, they can be cultured in medium with specific growth factors like VEGF, epidermal growth factor or bovine brain extract.
It takes the EPCs around 3 to 4 weeks to develop monolayers with endothelial appearance. They can also form capillary tubes in basement matrix gel, alone or with CD34-negative cells.
EPCs from AMSBIO
AMSBIO supplies Endothelial Progenitor Cells (EPC). These are similar to embryonic angioblasts and share features like:-
They are human primary cells
These are progenitor cells that have not been differentiated
They can differentiate into specific subtypes of endothelial cells forming veins, aortic or microvascular tissues
Their gene expression is similar to endothelial cells from tumors and they can specifically migrate to human tumors
The quantity and functions of the EPCs are altered when in human blood in presence of several diseases.
Potential applications of EPCs
There are several emerging applications of EPCs. Some of these include:-
Cancer drug discovery – EPCs can be used to study angiogenesis, impaired angiogenesis and angiogenesis inhibition, human ovarian cancer cell proliferation, and aggressive angiogenesis during tumor re-growth. They are particularly useful in breast cancer, lung cancer, lymphomas, inoperative hepatocellular cancers etc.
Cancer drug delivery systems
Repair of injured vessel wall
Neovascularization or regeneration of ischemic tissue
Coating of vascular grafts
Presence of diabetes mellitus, cerebrovascular disease, arthritis, pulmonary hypertension and ischemia.
Blood vessel disorders like coronary artery disease and acute myocardial infarction
Use in skin wound healing a skin regeneration
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