Blood vessels run through the entire body and transport nutrients and oxygen through the circulating blood. During vascularization, cells first form local lumens, which then fuse to form a continuous tubular network. The connections between the individual cells must be well sealed and stable to ensure vascular integrity and prevent leakage, and the formation of blood vessels is a complex process involving the interaction of proteins and mechanical forces.
Researchers at Oregon Health & Science University have discovered how specialized cells surrounding small blood vessels, known as perivascular cells, contribute to blood vessel dysfunction in chronic diseases such as cancer, diabetes and fibrosis (tissue alteration caused by abnormal connective tissue proliferation). The results published in Science Advances could change the treatment of these diseases.
How Perivascular Cells TriggerInflammation and Signal Changes in Blood Vessels
The study, led by Luiz Bertassoni, D.D.S., Ph.D., founding director of the Knight Cancer Precision Biofabrication Hub and professor at the OHSU Knight Cancer Institute and OHSU School of Dentistry, shows that perivascular cells sense changes in neighboring tissues and send signals that disrupt blood vessel function and exacerbate disease progression. Nearly a decade ago, Bertassoni and his team developed a method to 3D print blood vessels in the lab – a breakthrough that was recognized by Discover magazine as one of the most important scientific discoveries of the year.
Since then, they have focused on developing blood vessels that better mimic those in the human body to study more complex diseases. “In the past, endothelial cells, which line blood vessels, were thought to be the main cause of vascular disease,” says Bertassoni. The results represent a paradigm shift and show that perivascular cells instead act as important guardians.
They recognize changes in the tissue and coordinate vascular reactions. This opens the door to completely new treatment strategies. The potential applications of this research are manifold. The scientists have shown for the first time how perivascular cells trigger inflammation and signal changes in the blood vessels when the surrounding tissue is altered.
Discovery Could Lead to New Prevention and Treatment Strategies for Cancer, Diabetes, Fibrosis and other Diseases
The study used an innovative “blood-vessel-on-a-chip” model developed by Dr. Christopher Chen and his team at Boston University and the Wyss Institute at Harvard, who are collaborating on the project. By mimicking conditions such as tissue stiffening and scarring – common in aging, chronic disease and cancer – the researchers discovered that perivascular cells promote leakiness and distortion of blood vessels and exacerbate inflammation and disease. When the researchers removed perivascular cells, the blood vessels were essentially unresponsive to tissue changes.
The results shed light on the relationship between the extracellular matrix, blood vessel function and disease progression. Perivascular cells could become targets for therapies aimed at restoring normal vascular function and slowing the progression of various diseases such as fibrosis, diabetes and cancer. Importantly, the research also offers promising opportunities for cancer prevention and early intervention. Early detection and treatment of changes in these cells could help stop tumors before they grow.