Towards Creating Blood Vessels

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Researchers then looked for molecular triggers that ramp up endothelial differentiation and production. Shahin Rafii, a professor of medicine at Weill Cornell Medical College, and a Howard Hughes Medical Institute investigator, carefully selected various drugs and small molecules, and tested their effects in cultures of embryonic stem cells. Rafii found one candidate in particular that significantly boosted the yield of differentiated, committed endothelial cells.

This molecule, which goes by the technical label SB431542, is known to inhibit TGF-beta, a protein involved in cell differentiation and proliferation. Researchers found they were able to get the highest yield of endothelial cells when they first allowed TGF-beta to act uninterrupted, then introduced the inhibitor molecule to turn off TGF-beta at just the right time. Properly timed exposure to the TGF-beta inhibitor boosted production of endothelial cells 36-fold.

That increase could have real clinical significance, says Joseph Wu, assistant professor of medicine and radiology at Stanford University School of Medicine. "This new protocol is a significant advance, and a very good amplification process, because in order to translate therapy to humans and animals, you have to scale up the numbers," says Wu, who was not involved in the research. Heart grafts to treat cardiovascular disease, for example, would likely require 20 million to 50 million cells, he says.

The researchers now plan to determine whether the cells can actually restore blood flow to damaged tissue by injecting them into injured animals. The group is also working to grow engineered endothelial cells into functional blood vessels in vitro, on three-dimensional scaffolds that simulate the real conditions in the body. Sina Rabbany, a bioengineering professor at Hofstra University, is designing polymeric scaffolds, and growing endothelial cells on grafts of smooth muscle cells.

"Almost every body part requires a vascular supply, and endothelial cells are the building blocks of that supply," says Rabbany. "So now that we can make these cells, how can we make them grow in a 3-D setting and make conduits that carry blood, and can provide oxygen and nutrients to other cells? [Because] whether you want to grow a pancreas for diabetes, or help treat Parkinson's disease, every cell in the human body is next to an endothelial cell."