A team of bioengineers at the University of Washington has developed the first structure for growing small human blood vessels in the laboratory. The vessels behave remarkably like those in a living human and offer a better and much more modular approach to studying blood-related diseases, testing drugs and, one day, growing human tissues for transplant.
The past year alone has brought remarkable advances in blood vessel regrowth in the human body, ranging from regenerating bandages that can speed up angiogenesis (the growth of new blood vessels from pre-existing ones) to new ways of fighting myocardial ischemia disease.
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The University of Washington breakthrough, however, marks the first time that blood vessels are grown in the lab, allowing researchers to study much more extensively how conditions such as thrombosis and angiogenesis - but also cancer and the later stages of malaria - affect the circulatory system.
The microvessels behave remarkably like they would in the human body, sprouting new branches when in contact with stromal cells, reacting appropriately to clotting agents, and transporting blood even through sharp corners.
Researchers made a functional microvessel that spells the letters "UW." The white bar measures 100 micrometers, about the width of a human hair (Image: Y. Zheng, University of Washington)
Prof. Ying Zheng, who led the research, built the structure out of collagen, the most abundant protein in the body. She created tiny channels and injected them with human endothelial cells, which line the inside of human blood vessels. Over the course of two weeks, the endothelial cells grew throughout the structure, forming tubes through the mold's channels, just as they would in the human body. Then, brain cells were then injected in the collagen gel.
"The brain cells were injected into the gel to study how they interact with the innermost vessel cell - endothelial cells," Zheng told Gizmag. "Most of blood vessels are composed of endothelial cells and perivascular cells, and surrounding them there are stromal cells. The brain cells injected in the gel acted as perivascular cells that they coated around the endothelium, to stabilize the vessel barrier; they also acted as stromal cells to stimulate the endothelium to sprout new branches, extending the network."
The greatest advantage to this approach is that scientists can now effectively dissect what happens at the interface between the blood and the tissue, looking at how blood-related diseases progress and designing efficient strategies to contrast them.
"With this system we can isolate each component or we can put them together to look at a complex problem. We can isolate the biophysical, biochemical or cellular components. How do endothelial cells respond to blood flow or to different chemicals, how do they interact with their surroundings, and how do these interactions affect the vessels' barrier function? We have a lot of degrees of freedom," says Zheng.
The system could also be an accurate model for how tumors progress within the body. Cancer, in fact, secretes chemicals that cause nearby blood vessels to bulge and then sprout. Tumor cells then penetrate the bloodstream and colonize new parts of the body.
This mechanism can be modeled accurately by Zheng's system. When the researchers injected a signaling protein for vessel growth that's overabundant in cancer and other diseases, new blood vessels sprouted from the originals, and the new vessels exhibited similar characteristics to those in human cancers.
The short video below shows blood being pumped through one of the engineered vessels. This system has been injected with a compound associated with clotting, and clots were shown to form in these vessels just as they do in the human body. The blood was driven by an external gravity pump.
The researchers are now using the system to further explore the blood vessel interactions that cause inflammation and clotting, but even more exciting applications are on the horizon. "This vascular structure could serve as the infrastructure to support the human transplantable tissues. This is something we are working towards in the very near future," says Zheng.
The findings are published online on this week's edition of the journal Proceedings of the National Academy of Sciences.
Source: University of WashingtonView gallery - 3 images