Caption: Schematic of the fluid-filled space supported by a network of collagen bundles lined on one side with cells. Credit: Illustration by Jill Gregory and courtesy of Mount Sinai Health System


PHILADELPHIA – A system of interconnected, fluid-filled compartments lies below the skin’s surface, lining the digestive tract, lungs and urinary systems, and around arteries, veins, and the space between muscles, according to a research team from the Perelman School of Medicine at the University of Pennsylvania, Mount Sinai Beth Israel Medical Center, and the New York University School of Medicine. This system is a previously unknown feature of human anatomy and is described in Scientific Reports this week. The researchers believe these spaces are an extension of the interstitial space between organs, supported by a strong and flexible network of collagen and elastin, two connective tissue proteins.

Co-first author Rebecca Wells, MD, a professor of Gastroenterology, Bioengineering, and Pathology and Laboratory Medicine at Penn, determined that this interstitium is composed of these two proteins by examining human bile ducts.

The team suggests that this discovery has implications for the function of most organs and may play a role in the mechanism of many major diseases. In addition, they postulate that this network of fluid-filled spaces is important in understanding how cancer cells spread.

“It’s always been known that a so-called interstitial space feeds the lymphatic system, but it’s been defined as the space in between cells,” Wells said. “Our finding dramatically extends the concept of that space to include regions between and along tissues, as well as between cells. The fluid as well as the network-like organization of the collagen, in place of what was thought to be a dense wall of collagen, were a surprise.”

The team surmises that the fluid serves as a shock absorber because the places where it is found are all subject to movement of some kind, including peristalsis in the gut, pulsations of arteries, and contractions of bile ducts.

“The space is almost certainly present in all animals with a lymphatic system,” Wells said. She and colleagues are working on identifying the cells that adhere to the collagen bundles as these cells may be important for understanding some forms of fibrosis.

This work was funded in part by the National Institutes of Health (DK081523) and the NSF Center for Engineering MechanoBiology.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $496 million awarded in the 2020 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 44,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2020, Penn Medicine provided more than $563 million to benefit our community.

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