Researchers at Oregon Health and 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. The findings, published today in Scientific advancescould change the way these diseases are treated.
The study, led by Luiz Bertassoni, DDS, Ph.D., founding director of the Knight Cancer Precision Biofabrication Hub and professor at the OHSU Knight Cancer Institute and the OHSU School of Dentistry, shows that perivascular cells detect changes in nearby tissues and send signals that alter the function of blood vessels, worsening the progression of the disease.
Nearly a decade ago, Bertassoni and his team developed a method to 3D print blood vessels in the lab, a breakthrough recognized as one of the year’s top scientific discoveries by Discover magazine. Since then, they have focused on designing blood vessels that better mimic those of the human body to study more complex diseases.
“Historically, endothelial cells that line blood vessels have been considered the main contributors to vascular disease,” Bertassoni said. “Our findings represent a paradigm shift, showing how perivascular cells instead act as important sentinels. They detect tissue changes and coordinate vascular responses. This opens the door to completely new treatment strategies.”
Cristiane Miranda Franca, DDS, Ph.D., lead author of the study, is an assistant professor in the OHSU School of Dentistry and has appointments at the OHSU Knight Precision Cancer Biomanufacturing Center and the Early Detection Advanced Research Center Knight Cancer Institute, or CEDAR. .
“The applications of this research are broad,” he said. “We have shown for the first time how perivascular cells trigger inflammation and signal changes in blood vessels when surrounding tissues are disturbed.”
The study used an innovative “blood vessels on a chip” model developed by Christopher Chen, M.D., Ph.D., and his team at Boston University and the Wyss Institute at Harvard, who are collaborating on this project. By replicating conditions such as tissue hardening and scarring, common in aging, chronic diseases and cancer, researchers found that perivascular cells cause leaks and distortions of blood vessels, worsening inflammation and disease.
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“When we removed the perivascular cells, the blood vessels essentially did not respond to the changes in the tissues,” Franca said.
The findings 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 reducing the progression of various diseases such as fibrosis, diabetes and cancer.
Importantly, the research also holds promise for cancer prevention and early intervention. Early detection and treatment of changes in these cells could help stop tumors before they grow.
“If we intervene early, we could prevent precancerous lesions from progressing into full-blown cancer,” Bertassoni said. “This could revolutionize the way we approach cancer prevention and treatment.”
In addition to Bertassoni and Franca, OHSU co-authors include Maria Elisa Lima Verde, Ph.D., Alice Correa Silva-Sousa, DDS, Ph.D., Amin Mansoorifar, Ph.D., Avathamsa Athirasala, MS, Ramesh Subbiah , Ph.D., Anthony Tahayeri, BS, Mauricio Sousa, DDS, MS, Ph.D., May Anny Fraga, DDS, MS, Rahul Visalakshan, Ph.D., Aaron Doe, M.S., Keith Beadle, B.S., and McKenna Finley, B.A. Co-authors also include Emilios Dimitriadis, Ph.D., of the National Institute of Biomedical Imaging and Bioengineering; Jennifer Bays, Ph.D., and Marina Uroz, Ph.D., of Boston University; and Kenneth Yamada, M.D., Ph.D., of the National Institute of Dental and Craniofacial Research of the National Institutes of Health.