Researchers have discovered the role of specialized cells surrounding small blood vessels, called perivascular cells, in the impairment of blood vessels related to chronic conditions like cancer, diabetes, and fibrosis. This discovery may lead to new treatment approaches for these diseases.
A team from Oregon Health & Science University has revealed how perivascular cells, which envelop small blood vessels, contribute to blood vessel impairment found in chronic illnesses like cancer, diabetes, and fibrosis. The results, published today in Science Advances, could significantly influence treatment methods for these conditions.
Led by Luiz Bertassoni, D.D.S., Ph.D., the founding director of the Knight Cancer Precision Biofabrication Hub and a professor at both the OHSU Knight Cancer Institute and OHSU School of Dentistry, the study finds that perivascular cells are able to detect changes in their surrounding tissues and send signals that negatively impact blood vessel function, thereby exacerbating disease progression.
Nearly ten years ago, Bertassoni and his team created a technique to 3D print blood vessels in a laboratory setting — a groundbreaking achievement that was recognized as a top scientific advancement of the year by Discover magazine. They have since been dedicated to engineering blood vessels that closely resemble those in the human body to better explore complex medical conditions.
“Historically, endothelial cells that line blood vessels have been viewed as the primary contributors to vascular diseases,” Bertassoni noted. “Our research shifts this perspective, highlighting the critical role of perivascular cells as key monitors. They sense tissue alterations and coordinate vascular reactions. This discovery paves the way for innovative treatment options.”
The lead author of the study, Cristiane Miranda Franca, D.D.S., Ph.D., is an assistant professor at the OHSU School of Dentistry, with ties to the Knight Cancer Precision Biofabrication Hub and the Cancer Early Detection Advanced Research Center, or CEDAR.
“The implications of our research are extensive,” she emphasized. “We have demonstrated for the first time how perivascular cells initiate inflammation and signal changes in blood vessels when nearby tissues are affected.”
The study utilized an advanced “blood vessel on-a-chip” model crafted by Christopher Chen, M.D., Ph.D., and his colleagues from Boston University and the Wyss Institute at Harvard. By simulating conditions like tissue stiffening and scarring — prevalent in aging, chronic conditions, and cancer — the researchers found that perivascular cells promote blood vessel leakage and distortion, amplifying inflammation and deteriorating health.
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“When we removed perivascular cells, the blood vessels appeared incapable of responding to changes in tissue,” Franca explained.
The research insights illuminate the connection between the extracellular matrix, blood vessel functionality, and disease progression. Therefore, targeting perivascular cells may introduce new therapeutic strategies aiming to restore healthy vascular function and slow the progression of diseases like fibrosis, diabetes, and cancer.
Significantly, this research also opens avenues for cancer prevention and early intervention. By recognizing and addressing alterations in these cells sooner, there is potential to inhibit tumor development before it escalates.
“With early intervention, we may be able to stop precancerous changes from evolving into full-blown cancer,” Bertassoni said. “This could transform our strategies for cancer prevention and treatment.”
Along with Bertassoni and Franca, the OHSU research team includes Maria Elisa Lima Verde, Ph.D., Alice Correa Silva-Sousa, D.D.S., Ph.D., Amin Mansoorifar, Ph.D., Avathamsa Athirasala, M.S., Ramesh Subbiah, Ph.D., Anthony Tahayeri, B.S., Mauricio Sousa, D.D.S., M.S., Ph.D., May Anny Fraga, D.D.S., M.S., Rahul Visalakshan, Ph.D., Aaron Doe, M.S., Keith Beadle, B.S., and McKenna Finley, B.A. Additionally, co-authors from other institutions include Emilios Dimitriadis, Ph.D., from the National Institute of Biomedical Imaging and Bioengineering; Jennifer Bays, Ph.D., and Marina Uroz, Ph.D., from Boston University; and Kenneth Yamada, M.D., Ph.D., from the National Institute of Dental and Craniofacial Research under the National Institutes of Health.
