Endothelial cells derived from primate embryonic stem cells

Patent Number: 7,176,023

It is known that endothelial cell dysfunction is one of the major causes of morbidity and mortality in the Western world. For example, if endothelium could properly respond to the hypoxic conditions associated with cardiac angina and form new blood vessels, then heart disease would take such a heavy toll on today’s society. This is just a limited example, atherosclerosis, various tissue ischemias, as well as generalized organ failures have all been associated directly or indirectly with endothelial dysfunction.

In the current patent, the inventors demonstrate the ability to generate “new” endothelium from embryonic stem cells. This patent, which is owned by the same institution that owns the first issued ES patents, WARF, covers specific culture conditions for differentiation of ES cells into endothelium.

The patent teaches the culture of ES cells (human or primate) in various concentrations of VEGF, IGF, EGF, and bFGF in order to obtain some cells with endothelial morphology. Once these cells are obtained, they are further cultured in order to generate a population of endothelial cells that are over 90% pure. The morphology of the endothelial cells derived using this method is claimed to be elongated or stellate shaped, this the inventors contrast with the morphology of the ES cells, which are non-elongated. Various characteristics of the generated endothelial cells are described by the inventors in the patent. These include: vWF+, Alpha v Beta 3+, CD146+, VE cadherin-, CD31- ability to bind UEA-1 (a special lectin), ability to uptake acetylated LDL, ability to form pipe-like structures when placed in Metrigel, and ability to induce vascularization of a tumor in a SCID mouse.

These features of course pose certain questions, such as, why do they not express CD31, which to our knowledge is usually expressed on endothelium? Additionally, if the cells can vascularize a tumor, maybe these cells have certain carcinogenic potential?

View this patent on the USPTO website.