A previously unknown function of blood vessels has been found. Beside supplying blood, they guide the formation of the pancreas and possibly other organs during the development of embryos, according to researchers at Harvard University.
Their experiments document a key role played by the lining of blood vessels in the formation of a pancreas and its insulin-producing cells. Although the work was done with mouse embryos, the researchers believe their discovery could lead to new treatments for diabetes in humans.
“Blood vessels, still under development themselves, send out signals that guide formation of the pancreas,” says Douglas Melton, Cabot Professor of Natural Sciences. “When we determine exactly what these signals are, we should be able to see how islet cells develop to secrete insulin. That, in turn, could open the way to finding new treatments for millions of diabetics.”
Melton also predicts that the organs of all vertebrate animals, from frogs to humans, develop in the same way. If he is right, the discovery will add to the fundamental knowledge of how humans and other backboned animals grow in the womb. It could also point the way to novel treatments for diseases of organs such as the lungs, liver, and stomach.
Details of this research, done by Melton and two postdoctoral students, Eckhard Lammert and Ondine Cleaver, are published in the Sept. 28 issue of Science.
How a pancreas forms
Melton estimates that being able to manipulate the development of insulin-producing cells could help all those with juvenile, or Type 1, diabetes and about 10 percent of people with adult-onset, or Type 2, diabetes.
It was once thought that organs develop first, then send out signals that attract blood vessels to grow into them and provide nourishment. “Our work indicates that the two develop together,” Melton explains. These vessels not only carry blood, but cells that make up their inner lining secrete proteins needed for the pancreas to form.
At this time in life, a mouse or human embryo has a long tube running from what will be a mouth to what will be an anus. Blood vessels, which consist of only a single layer of cells, come into contact with the tube and secrete an as-yet-unknown substance that leads buds to form on the tube. These buds then form so-called islet cells, a key part of the pancreas. If all goes well, islet cells produce enough insulin to handle the sugar that people eat and turn it into energy. When the islets cannot produce enough insulin, diabetes occurs.
“If you’re trying to prove that blood vessels influence this process, one way to do it is to remove blood vessels in contact with the gut,” Melton notes. Lammert and Cleaver did this in frog embryos and found that no islet cells developed.
Also, if blood vessels make islet cells, the more blood vessels added to an embryo the more islet cells should be produced. When this is done in mice, large numbers of islet cells formed not only where they are supposed to form, but insulin is produced in other areas of the gut where islet cells don’t normally exist.
Finally, gut tissue from mice that have human genes was grown in lab dishes without the benefit of contact with blood vessel cells. No insulin was produced. The researchers then added blood vessel tissue, and a pancreas began to develop. This experiment shows that it is not just blood causing the growth but cells that will later become the inside lining of blood vessels.
Looking for factor X
What exactly is the signal that blood vessel cells send to stimulate formation of a pancreas? “It probably is a protein secreted by the cells,” Melton answers. “We call it ‘factor X’ because we don’t yet know what it is. Finding out is the next challenge.”
Although his team has uncovered a previously unknown function performed by blood vessels during development, Melton refers to the discovery as “only one step in the process of forming the pancreas. We expect, however, that it will inspire other researchers to find other steps that involve not just the pancreas but organs common to all vertebrates. That, in turn, should lead to new treatments for the many diseases that affect other organs that grow from the same primitive tube, including the liver, lungs, and stomach.”