Scientists are interested in finding new technologies to study blood vessels for several reasons:
- Heart disease and clogged arteries are a major cause of disability and death due to heart attacks and strokes. Drugs to treat heart disease and high blood pressure act on the cells of blood vessels.
- Blood vessels transport drugs throughout the body, bringing the drugs to organs or tissues where they are needed.
- Drugs used to treat childhood cancers can damage the cells lining blood vessels, increasing the risk for cardiovascular disease.
- Many cancerous tumors secrete growth factors to stimulate the development of blood vessels. This process diverts nutrients and oxygen away from healthy tissues to support the abnormal, rapid growth of the cancer. In addition, the cancer can metastasize (spread) to other areas of the body through blood vessels. Patients could benefit from treatments that stop the growth of these blood vessels.
NIH-supported scientists are developing a series of human tissues and organs on chips for testing the safety and effectiveness of potential new treatments, and these systems also can help researchers study diseases. Several of these organs on chips include blood vessels to ensure that the living tissues continue to function and allow drugs to travel as they would in the human body.
Blood Vessels on a Chip
Through bioengineering — the science of creating complex, functional tissue from cells — Duke University scientists have generated human blood vessels on a chip. Not only can the bioengineered vessels deliver oxygen and nutrients into the tissue, but they also can contract and dilate just like blood vessels in the human body do to help regulate body temperature and metabolism.
The photo above shows a bioengineered blood vessel developed by the Duke University team.
The video above shows white blood cells (fluorescing red) passing through the vessel. The white blood cells (red) can attach to the blood vessel wall (blue) and travel into the tissue to fight infection, similar to what occurs in the body.
Microvessels on a Chip
In a complementary NIH-funded project, researchers at Washington University in St. Louis and the University of California, Irvine, are developing a microvasculature model that would work much like the tiny blood vessels in the body. The microvessels could be integrated with several different human organs on chips, including liver, kidney, muscle, gastrointestinal system and reproductive system to deliver oxygen and nutrients to tissues.
To create the microvasculature system, the scientists used a special technique to generate induced pluripotent stem cells (iPSCs) from adult cells. Stem cells have the remarkable potential to develop into many different cell types. Stem cells are important during early life and for embryonic growth; in adults, stem cells function in tissue repair and maintenance. iPSCs can produce an unlimited supply of donor cells capable of forming blood vessel and other types of tissues for the chip devices.
Scientists are using the microvasculature technology to study the delivery of anticancer drugs to various tissues and how tumor cells use blood circulation to move from one site to another in the body (metastasis). Researchers want to learn more about the effects of these drugs before they are used in humans; this technology potentially could make drug testing faster and more accurate.
In the left image, microvessel networks are labeled with a green fluorescent dye. In the right image, microvessels (red) are networked into human heart tissue (green).
Functional microvessels derived from induced pluripotent stem cells form networks capable of fluid flow. In this video, fluorescent purple beads show functional flow in the vessels. Colon cancer cells (green) can grow nearby, mimicking the human cancer microenvironment.
Techniques for Developing Microvessels
Another NIH-supported teams of scientists at Columbia University, Boston University, the Wyss Institute at Harvard University, the Massachusetts Institute of Technology and Yale University are using tiny systems to develop microvessels. By applying micro- and nanofabrication tools to manipulate the adhesive and mechanical environment of cells, along with traditional molecular approaches, the researchers can grow microvasculature within a lattice structure.
NIH-supported scientists have designed functional blood vessels using a degradable lattice structure. The top image shows how fluorescent fluid flows through the vessel. The bottom image shows the vessel leaking when thrombin is added, just as it would in the human body.
This video shows green fluorescent beads flowing through the microvessel.
Looking Ahead
The teams of researchers working on blood vessels and microvasculature envision using the technologies to link other tissue chip devices. The result would be a continuous network linking multiple organs. With such a system, scientists could learn about new drugs’ effects on different parts of the human body before testing them in people.
Testing drugs in human tissue may better reflect the drugs’ effectiveness and toxicities in humans. This process could enable researchers to gather data to accelerate the drug approval process and subsequently make new treatments available sooner to patients.