Meet Your Interstitium, a Newfound "Organ" - S... https://www.scientificamerican.com/article/meet...

THE BODY

Meet Your Interstitium, a

Newfound "Organ"
These fluid-filled spaces were found in the body’s connective tissue

By Rachael Rettner, LiveScience on March 27, 2018

Credit: Getty Images

With all that’s known about human anatomy, you wouldn’t

expect doctors to discover a new body part in this day and age.
But now, researchers say they’ve done just that: They’ve found
a network of fluid-filled spaces in tissue that hadn’t been seen
before.

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These fluid-filled spaces were discovered in connective tissues

all over the body, including below the skin’s surface; lining
the digestive tract, lungs and urinary systems; and surrounding
muscles, according to a new study detailing the findings,
published today (March 27) in the journal Scientific Reports.

Previously, researchers had thought these tissue layers were a

dense “wall” of collagen—a strong structural protein found in
connective tissue. But the new finding reveals that, rather than
a "wall,” this tissue is more like an “open, fluid-filled highway,”
said co-senior study author Dr. Neil Theise, a professor of
pathology at New York University Langone School of Medicine.
The tissue contains interconnected, fluid-filled spaces that are
supported by a lattice of thick collagen “bundles,” Theise said.

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The researchers said these fluid-filled spaces had been missed

for decades because they don’t show up on the
standard microscopic slidesthat researchers use to peer into the

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cellular world. When scientists prepare tissue samples for these

slides, they treat the samples with chemicals, cut them into thin
slices and dye them to highlight key features. But this fixing
process drains away fluid and causes the newfound fluid-filled
spaces to collapse.

Rather than using such slides, the researchers discovered these

fluid-filled spaces by using a new imaging technique that allows
them to examine living tissues on a microscopic level.

The researchers are calling this network of fluid-filled spaces an

organ—the interstitium. However, this is an unofficial
distinction; for a body part to officially become an organ, a
consensus would need to develop around the idea as more
researchers study it, Theise told Live Science. The presence of
these fluid-filled spaces should also be confirmed by other
groups, he added.

Official designation aside, the findings may have implications

for a variety of fields of medicine, including cancer research,
Theise said. For example, the findings appear to explain why
cancer tumors that invade this layer of tissue can spread to the
lymph nodes. According to the researchers, this occurs because
these fluid-filled spaces are a source of a fluid called lymph and
drain into the lymphatic system. (Lymph is a fluid that contains
infection-fighting white blood cells.)

A NEW ORGAN?

The human body is about 60 percent water. About two-thirds of

that water is found inside cells, but the other third is outside
cells and is known as “interstitial” fluid. Although researchers

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already knew that there is fluid between individual cells, the

idea of a larger, connected interstitium—in which there are
fluid-filled spaces within tissues—had been described only
vaguely in the literature, Theise said. The new study, he said,
expands the concept of the interstitium by showing these
structured, fluid-filled spaces within tissues, and is the first to
define the interstitium as an organ in and of itself.

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The new work is based on the use of a relatively new technology

called a “probe-based confocal laser endomicroscopy” or pCLE.
This tool combines an endoscope with a laser and sensors that
analyze reflected fluorescent patterns and gives researchers a
microscopic view of living tissues.

Back in 2015, two of the study authors—Dr. David Carr-Locke

and Dr. Petros Benias, both of whom were at Mount Sinai-Beth
Israel Medical Center in New York City at the time—were using
this technology when they saw something unusual while

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examining a patient’s bile duct for cancer spread. They spotted

a series of interconnected cavities in the tissue layer that didn’t
match any known anatomy, according to the report. When a
pathologist made slides out of this tissue, the cavities
disappeared—a mystery that was later found to be a
consequence of the slide-making process.

In the new study, the researchers first used pCLE on cancer

patients who were undergoing surgery to remove the pancreas
and the bile duct. The imaging technique indeed showed the
fluid-filled spaces in the connective tissue. When the tissue
samples were removed from the body, they were quickly frozen,
which allowed the fluid-filled spaces to stay open so the
researchers could see them under a microscope.

Later, the researchers saw these same fluid-filled spaces in

other samples of connective tissue taken from other parts of the
body, in people without cancer, Theise said. “The more tissues I
saw, the more I realized it’s everywhere,” he said.

The researchers think that the fluid-filled spaces may act as

shock absorbers to protect tissues during daily functions, the
researchers said.

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Theise noted that there may be quite a bit of information

already known about this fluid-filled space; it’s just that
researchers “didn’t know what they were looking at.” Indeed,
the researchers plan to conduct a review of the scientific
literature “for all the things we know about this [body part] but
didn’t know we knew it,” Theise said.

NEW QUESTIONS

The idea presented in the study appears to be “a completely

new concept,” said Dr. Michael Nathanson, chief of the
digestive diseases section at Yale University School of Medicine,
who was not involved with the study. “From the evidence they
presented it’s quite possible they’re correct,” Nathanson told
Live Science.

Previously, physicians had a somewhat nebulous

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understanding of the interstitial space, Nathanson said. They

knew it was a space with fluid found outside the cells, but no
one had ever entirely explained what this means. The new study
“did a nice job" of trying to define it, he said.

The findings are consistent with what Nathanson and

colleagues observed in a study published in 2011. At that time,
Nathanson and colleagues observed a network of dark fibers,
but they weren’t able to figure out exactly what it was. “I was
pleased that they substantiated our impression that this
network exists” and were able to define it, Nathanson said.

The new finding “allows us ask all kinds of questions we didn’t

even know to ask beforehand,” Nathanson said. For example,
could this area become altered in disease, or play a role in
driving disease, he said.

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Copyright 2018 LiveScience.com, a Purch company. All rights

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rewritten or redistributed.

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ABOUT THE AUTHOR(S)

Rachael Rettner

LiveScience

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