Some discoveries change the way we view the human body.
In 2021, researchers described what they saw when they had examined skin-biopsy samples that included tattoos: The ink particles had traveled deeper than anticipated, through interstitial spaces into the tissue underneath the skin, or the fascia.
“That wasn’t supposed to happen,” Neil Theise, a professor of pathology at New York University and a senior author of the paper reporting the results, told me.
The existence of an apparent conduit between skin and the fascia beneath it — two tissue layers not known to connect with each other in this way — broke accepted anatomic boundaries.
The researchers also found that the same was true for other previously unknown microscopic connections between organs in the abdomen.
That interstitial spaces exist in and under the skin and between and around the body’s organs had been observed going back more than a century, but they were assumed to exist in isolation from one another, like a patchwork quilt.
Theise and his colleagues published their first observations of these spaces in 2018. Their findings in the 2021 tattoo-ink study implied that the body’s interstitial spaces were parts of a vast interconnected whole — what scientists now call the interstitium.
“This is clearly a third bodily system for the circulation of fluids,” in addition to the cardiovascular and lymphatic systems, says Rebecca Wells, a professor of medicine at the University of Pennsylvania and a senior author of the study. The human body suddenly looked less like a patchwork quilt and more like a knitted blanket.
The implications of a new circulatory system — for our health, and for our understanding of our own bodies — are potentially enormous.
By Avraham Z. Cooper Illustrations by Jérôme Berthier May 11, 2026
For 400 years, anatomists have understood there to be two systems in the body that function as transportation networks for cells, electrolytes, nutrients and hormones: the lymphatic system and the cardiovascular system.
The lymphatic system, which removes excess fluid from tissues, was observed as early as 1622 by the Italian physician Gaspare Aselli when he vivisected a dog.
The workings of the cardiovascular system, in which the heart pumps blood through arteries, capillaries and veins, were first described in 1628 by the English physician and anatomist William Harvey.
We have also known, starting with its description more than a century ago by an American anatomist and pathologist named Franklin Mall, that a fibrous connective tissue enwraps and undergirds the internal structures in the human body: organs, nerves, blood vessels, bone, muscle.
This ubiquitous fibrous tissue, the fascia, functions in the body the way studs frame the rooms in a house. But these studs and the interstitial spaces inside them weren’t thought to be interconnected within and between organs — to form an interstitium network — until Theise and Wells’s study was published.
To get a sense of the inside of the interstitium, Wells suggests picturing a sheet of chicken wire embedded in a gel.
The chicken wire represents collagen, a type of protein. Inside the interstitium, bundles of collagen interlock with one another, providing strength and structure.
The spongelike gel, able to absorb and store water, is made from hyaluronic acid and fills the spaces between the collagen bundles.
Fluid, cells and other molecules slowly flow through this gel.
In this new view of the body’s interstitial spaces, these microscopic areas connect to one another within a larger web, through which fluid moves before re-entering the lymphatic and cardiovascular systems,
like groundwater flowing through the Earth’s crust before returning to the surface in springs and rivers.
Theise, Wells and colleagues were praised by their scientific peers for their findings. “This work was really comprehensive,” says David Merrick, an assistant professor of medicine at the University of Pennsylvania. But the idea of there being a circulatory system involving the body’s connective tissues was not unfamiliar to some medical systems.
“This knowledge is actually quite ancient,” says Leah Welsh, an osteopathic physician and an assistant professor of family and community medicine at Ohio State. “It’s something that other systems of medicine have been offering for a long time, but they didn’t have microscopes.”
As Theise told an interviewer from “Radiolab” in 2023, an expert in traditional Chinese medicine approached him at a conference in China where he was speaking on the interstitium and said, “We’ve been talking about it for 4,000 years.”
One of the most intriguing areas of current research is whether there is a connection between the interstitium and the ancient Chinese practice of acupuncture.
Acupuncture is used to treat conditions as varied as chronic pain, migraines, seasonal allergies and nausea caused by chemotherapy, but some of its actions have never been completely explained. The discovery of the interstitium may help us understand in modern biomedical terms how acupuncture works.
The principles of the practice invoke two circulating elements: chi and blood.
Traditional Chinese medicine describes chi as flowing along one of 12 main tracks, called meridians.
Acupuncturists insert small needles into specific points on the body to enhance the flow of chi.
In a 2002 study, Helene Langevin and Jason Yandow mapped the locations of acupuncture points in the arms to the fascia between and around muscles.
These acupuncture points have since been found to lie within the same areas of connective tissue where fluid flows through the interstitium.
A 2019 paper by researchers in China, led by Dr. Hongyi Li, explains how they injected chemical tracers into acupuncture points in the hands and feet of cadavers and used chest compressions to push fluid through the bodies.
Fluorescent photography enabled them to see the tracers traveling toward the heart within interstitial spaces of the arms and legs. Li and colleagues clearly recognized, just as Wells and Theise did, that they had glimpsed evidence of an interstitial circulation system.
If acupuncture points seem to reside within the interstitium, could the meridians run through the interstitium as well?
In 2021, a group of researchers conducted a similar experiment in China on living subjects, injecting dye into acupuncture points in the forearms of 15 volunteers.
In almost all of them, the dye slowly migrated upward along a route corresponding to the pericardium meridian, which passes through the wrist and along the inner arm.
(Pericardium is the same meridian stimulated by anti-nausea wrist acupressure devices popular on cruise ships.)
“This pathway doesn’t go in the veins, it doesn’t go superficially,” says Andrew Ahn, the study’s senior author and an assistant professor at Harvard Medical School. It goes instead, he told me, into the interstitium between the muscles: “When I saw that, I said: ‘We’re onto something. This truly has to do with acupuncture.’”
“I actually do think that the interstitium could be the link between Eastern and Western medicine,” Wells told me. “But you have to show scientifically that that’s the case.”
Much more research is needed to begin to understand the full implications of the discovery of an interconnected interstitium, but there are some promising leads.
Research in animals led by Merrick suggests that when a person gains weight, specialized cells in the interstitium around body fat can be called upon to make healthy fat cells, which are a key factor in fending off Type 2 diabetes.
Tipping these specialized cells toward the production of more healthy fat could offer a target for potential diabetes therapies.
Wells, who is a gastroenterologist, says that interstitial links may help explain why some patients with inflammatory bowel diseases, particularly ulcerative colitis, develop an autoimmune disease that affects the bile ducts.
It has been theorized that in inflammatory bowel disease immune cells, gut bacteria or bacterial fragments that migrate from the intestines to the liver end up reaching the bile ducts through the interstitium.
An interconnected interstitium also seems to play a critical role in cancer metastasis. It is well established that cancer cells can spread to the rest of the body by hijacking the lymphatic system.
But evidence suggests that tumor cells may reach the lymphatic system by first navigating through the fluid flowing through the interstitium, like fish swimming downstream.
Numerous cancer types have been seen spreading through the interstitium, breaking down hyaluronic acid as they spread. These include breast, lung, colon, pancreatic and skin cancers, among others, according to Theise.
A drug called narmafotinib, which disrupts how tumor cells invade and move through the interstitium, has shown promise in early clinical trials for treating pancreatic cancer, when combined with chemotherapy.
The discovery of a third circulatory system could transform our understanding of how the human body works. And it may also change how we view our own bodies in relation to other biological systems.
Wells points out that hydra — tiny freshwater invertebrates — have fluid-filled connective tissue called mesoglea that, like the interstitium, contain collagen and a gel-like substance similar to hyaluronic acid.
Plants seem to possess their own version of an interstitium, too. It’s called the apoplast, a type of interstitial space that transports water and nutrients outside cell membranes.
These and other examples suggest that fluid moving through interstitial spaces might have represented the first circulatory systems to develop in the earliest forms of complex multicellular plant and animal life, hundreds of millions of years ago.
This relatively recent discovery may have opened up new research frontiers that connect to some of the most ancient life-forms on our planet.
Avraham Z. Cooper, a pulmonary and critical care physician, is an associate professor of medicine at Ohio State University.
Jérôme Berthier is a visual artist and illustrator living in Vancouver, Canada, and the author of the comic “Myth.”