New insights on conditions for new blood vessel formation

June 25, 2014 by Evan Lerner
New insights on conditions for new blood vessel formation
A new capillary sprouting off a blood vessel.

(Medical Xpress)—Angiogenesis, the sprouting of new blood vessels from pre-existing ones, is essential to the body's development. As organs grow, vascular networks must grow with them to feed new cells and remove their waste. The same process, however, also plays a critical role in the onset and progression of many cancers, as it allows the rapid growth of tumors.

With lifesaving applications possible in both inhibiting and accelerating the creation of new blood vessels, a more fundamental understanding of what regulates angiogenesis is needed. Now, researchers at the University of Pennsylvania, Boston University and Harvard University have uncovered the existence of a threshold above which fluid flowing through causes new capillaries to sprout.

This discovery could help pave the way for cancer-fighting drugs, treatments for the hardened blood vessels found in the cardiovascular disease arthrosclerosis or even growing synthetic organs in the lab.

The research was led by postdoctoral fellow Peter Galie of the Department of Bioengineering in Penn's School of Engineering and Applied Science and Christopher Chen, then a professor of bioengineering at Penn who is now at Boston University and an associate faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University. They collaborated with Duc-Huy Nguyen, Colin Choi and Daniel Cohen, all members of Chen's lab, and professor Paul Janmey, also of the Department of Bioengineering, as well as the Department of Physiology in Penn's Perelman School of Medicine.

Their study was published in the Proceedings of the National Academy of Sciences.

The team's experiments incorporated "blood-vessel-on-a-chip" devices, which use microfluidic technology to simulate processes that normally occur deep within tissues. They found that cells lining each artificial vessel sprouted to form new vessels once the force exerted by fluid flow through the vessel exceeded a certain threshold.

"These findings suggest that our can sense when blood flow exceeds their carrying capacity and respond by producing additional vessels on demand," Chen explained. "Perhaps we could one day take advantage of this response to enhance vessel regrowth where the need is critical, such as after a heart attack."

During their experiments, the researchers controlled the within the artificial vessel, and ultimately where new vessels would sprout, by changing the shape and orientation of thin needles deployed within a collagen gel containing each vessel. Using a mathematical model, they predicted the exact spots along the vessel where force exceeded the sprouting threshold, thereby pinpointing the location where new vessels would form.

Now the researchers aim to advance new experiments designed to figure out how cells sense this mechanical threshold.

"The logical next step is to determine the molecular mechanism behind this phenomenon," said Galie, "what proteins are involved and how might they be targeted in new drug therapies."

Their work was funded by the National Institutes of Health and the University of Pennsylvania's Center for Engineering Cells and Regeneration, where Chen was the founding director.

Explore further: Starving pancreatic cancer before it has a chance to feast

More information: Peter A. Galie, Duc-Huy T. Nguyen, Colin K. Choi, Daniel M. Cohen, Paul A. Janmey, and Christopher S. Chen. "Fluid shear stress threshold regulates angiogenic sprouting." PNAS 2014 ; published ahead of print May 19, 2014, DOI: 10.1073/pnas.1310842111

Related Stories

Starving pancreatic cancer before it has a chance to feast

June 23, 2014

(Medical Xpress)—Pancreatic cancer's low survival rate gives researchers from The University of Kansas Cancer Center even more reason to find a way to prevent and treat the hard-to-detect cancer. Drs. Snigdha Banerjee, ...

Experts unlock key to blood vessel repair

June 10, 2014

Scientists from the University of Leeds have found a way to restore the function of damaged blood vessel repairing cells, in a potentially important step for the future treatment of heart disease.

Recommended for you

Natural compound reduces signs of aging in healthy mice

October 27, 2016

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency ...

A metabolic switch to turn off obesity

October 27, 2016

You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 ...

Scientists develop 'world-first' 3-D mammary gland model

October 27, 2016

A team of researchers from Cardiff University and Monash Biomedicine Discovery Institute has succeeded in creating a three-dimensional mammary gland model that will pave the way for a better understanding of the mechanisms ...

Mitochondria control stem cell fate

October 27, 2016

What happens in intestinal epithelial cells during a chronic illness? Basic research conducted at the Chair of Nutrition and Immunology at the Technical University of Munich (TUM) addressed this question by generating a new ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.