An efficient new method of making endothelial cells, which give rise to blood vessels, could prove a huge boost for tissue engineering and regenerative medicine. By first finding a way to effectively tag endothelial cells, researchers at Weill Cornell Medical College developed a simple way to increase production of these cells by more than 30-fold. The cells might one day by used to create blood vessels in engineered tissue or administered to patients directly to repair injury after heart attack or stroke, resupplying blood to damaged organs.
“[Eventually], we want to be able to inject slurries of these cells into people who have suffered heart attacks, and allow those tissues to recuperate by renewed blood flow,” says Daylon James, assistant research professor in the department of reproductive medicine at Weill Cornell Medical College, who led the research.
Our bodies house billions of endothelial cells, which line the interior of blood vessels. This vast network is responsible for maintaining vascular health, controlling blood pressure, managing clotting, and giving rise to new blood vessels. While researchers already knew how to turn embryonic stem cells into endothelial cells, the challenge has been a matter of commitment and scale. Once stem cells turn into endothelial cells, it’s difficult to make them stay that way. Getting endothelial cells to expand to numbers great enough to engineer functional artificial blood vessels has been another major roadblock.
While previous methods produced about 0.2 endothelial cells for every embryonic stem cell, James and his colleagues have found a much more efficient way to make committed endothelial cells. The new technique yields seven endothelial cells for every stem cell, according to research published in the advanced online edition of the journal Nature Biotechnology. When these differentiated cells were injected into mice, they formed tiny, capillary-like structures.
To create the new method, the team first developed a way of identifying endothelial cells among cultures of differentiating embryonic stem cells. James recognized a gene called VE-cadherin that only appears in endothelial cells, making it an ideal marker. He then genetically engineered a green fluorescent protein to turn on in embryonic stem cells only when VE-cadherin is expressed, signaling in real time that the stem cell has differentiated into an endothelial cell.