New Human 'Organ' Was Hiding in Plain Sight



Original post written by Sarah Gibbens for National Geographic

Lurking just under your skin might be a new organ only now identified for the first time, say a team of scientists. 

In a new study published in the journal Scientific Reports, researchers from New York University's School of Medicine say they have found a new organ they're calling the "interstitium." 

It's nearly everywhere—just below the skin's surface, surrounding arteries and veins, casing the fibrous tissue between muscles, and lining our digestive tracts, lungs, and urinary systems. 

It looks like a mesh. The interstitium is a layer of fluid-filled compartments strung together in a web of collagen and a flexible protein called elastin. Previously, scientists thought the layer was simply dense connective tissue. 

The organ has seemingly been hidden in plain sight, and scientists say they missed it because of the way tissue is studied. Before being placed under a microscope, samples are thinly sliced and treated with chemicals that allow researchers to identify key components more easily. While the process is helpful for more easily spotting details, it drains fluid from the sample. 

Devoid of their fluid, the compartments collapse, like a building with the floors suddenly knocked out, leaving the whole structure to flatten like a pancake. 

To find these pockets of interstitial fluid, medical researchers looked at living tissue instead of sampling dead tissue samples. They did this by using a probing technique called confocal laser endomicroscopy. The method entails using a tiny camera probe that takes a microscopic look around a human body. Tissue is lit by the endoscope's lasers and the fluorescent patterns it then reflects are analyzed by sensors. 


Asterisks denote collagen bundles (top left). An arrow points to a cell (top right). Darker blue shows collagen bundles, and light blue reveals what may be elastin (bottom left). Elastin fibers shown in black run along collagen bundles shown in pink (bottom right).

Asterisks denote collagen bundles (top left). An arrow points to a cell (top right). Darker blue shows collagen bundles, and light blue reveals what may be elastin (bottom left). Elastin fibers shown in black run along collagen bundles shown in pink (bottom right).

Accidental Discovery

Scientists first noticed the compartments when looking at a bile duct. They saw what they thought might be tears in dense tissue. The images were taken to Neil Theise, a professor at NYU's School of Medicine and author on the paper. 

"You're talking about the remaining extracellular fluid that's unaccounted for," Theise says. About 70 percent of the human body is made of water, and about two thirds of that is found in cells. The remaining third, says Theise, is only partially known. 

In addition to accounting for bodily fluid, the compartments may help explain essential functions. 

"It's like a shock absorber," says Theise. "Not a hard, stiff material." 

Among Theise's theories for the purpose of the interstitium is that it's a source of lymph, a fluid that moves through the body's lymphatic system and supports immunity. He says that knowing how diseases spread through this part of the body could help researchers better understand how cancer spreads. 

"Can we detect [disease] earlier by sampling fluid from the space? Can we figure out mechanisms to stop spread?" He asks. 


Promise and Skepticism 

Jennifer Munson is a biomedical engineer at Virginia Tech who has looked at fluid in the body. She was not involved with the study but says its findings are promising. 

"I think what the paper shows is the benefit of having new ways to image and look at tissues. [Previous methods] dehydrate the tissues, and you lose so much structural information," Munson notes. 

She says she's fairly convinced these structures exist but wants to see more research before speculating on what they do, and whether its accurate to call them a new organ. 

"I'm really excited about the find but, as with all scientists, I approach everything with a little skepticism," she adds. 

Theise says he's aware of some of the skepticism surrounding his findings, but it's territory he's not shy about wading into. In 2005, he wrote an essay in Naturechallenging the importance of "cell theory"—a concept that holds cells as the basic structure of all organisms, and in 2001, he published a paper finding that adult stem cells could be made to act similarly to embryonic cells. 

"There's always going to be stuff we haven't seen before that we don't know," he adds. "I'm awestruck that nature is more complicated than we allow ourselves to think." 


Newfound 'organ' could be the biggest in your body


Original post written by Jacqueline Howard for CNN

(CNN) To be or not to be an organ: That is the question.

Researchers have detailed the structure and distribution of spaces in your body that they say represent a newfound human organ, and this "organ" just might be your body's biggest -- but not all experts are convinced.

It's the part of the body known as the interstitium, a name for widespread, fluid-filled spaces within and between tissues all over your body, according to a study published in the journal Scientific Reports on Tuesday.

Doctors and scientists have known about interstitial tissue and interstitial fluid, but the study provides fresh insights into a previously unrecognized feature of humananatomy -- and the researchers are raising the idea of calling the interstitium an "organ."

"Initially, we were just thinking it's an interesting tissue, but when you actually delve into how people define organs, it sort of runs around one or two ideas: that it has a unitary structure or that it's a tissue with a unitary structure, or it's a tissue with a unitary function," said Dr. Neil Theise, professor of pathology at NYU Langone Health in New York, who was a co-senior author of the study.

"This has both," he said of the interstitium. "This structure is the same wherever you look at it, and so are the functions that we're starting to elucidate."

Additionally, "I think it's bigger than the skin," he said. The skin, comprising roughly 16% of your body mass, is thought to be your largest organ. As for the interstitium, "my estimate is that 20% of the volume of the body is this, which is equivalent to about 10 liters in a young adult."




'Once you see it, you can't unsee it'

For the study, Theise and his colleagues used a powerful microscope with a technique called confocal laser endomicroscopy to examine and analyze healthy living tissue samples from human bile ducts. The samples were taken from 13 patients undergoing pancreatic surgeries at Mount Sinai Beth Israel in New York. 

The samples were infused with a fluorescent liquid, allowing the researchers to see every detail. They wrote in the study that they observed spaces where fluid accumulates. Those spaces appeared to be pre-lymphatic, meaning they appeared to drain into lymph nodes.

Traditionally, when such tissue samples are examined under a microscope, the tissues are dehydrated and look like dense layers, Theise said. So the interstitium could have gone previously unnoticed because it was collapsed due to dehydration.

"Now, it's clear that by looking in the living tissue at the microscopic level with this new confocal laser endomicroscopy ... that space is fully expanded and filled with fluid," he said. "Once you see it, you can't unsee it."

Theise described encountering this new view of the interstitium as a moment of "quiet awe."

The interstitium is seen here beneath the top layer of skin but is also in tissue layers lining the gut, lungs and urinary systems, as well as those surrounding blood vessels and the fascia between muscles.

More research is needed to better understand the true function of the interstitium, how it impacts other parts of the body and the disagreements over its organ status.

After all, "I would think of this as a new component that is common among a variety of organs, rather than a new organ in and of itself," said Dr. Michael Nathanson, professor of medicine and cell biology and chief of the section of digestive diseases at Yale University School of Medicine, who was not involved in the study.

"It would be analogous to discovering blood vessels for the first time, in that they are in every organ but they aren't an organ themselves," Nathanson said.

"In my opinion, this has the potential to change our understanding of the human body because this 'pre-lymphatic region,' as the authors refer to it, may undergo changes in certain diseases states such as certain types of cancer," he said. "So this now puts us in a position to figure out whether this is an effect or else perhaps part of the cause of such diseases."


Shedding light on how cancer spreads

The new study suggests that interstitium spaces may play a role in helping cancer cells spread around the body, becoming metastatic, Theise said.

"It's been known that when cancer invades this layer, either in the skin or in the viscera, that's when it first becomes able to spread outside the organ of where it arose," he said.

When cancer cells break away from a tumor, they can travel to other parts of the body through the bloodstream or the lymph system, according to the American Cancer Society. Since interstitium spaces might act as conduits, "this raises the possibility that direct sampling of the interstitial fluid could be a diagnostic tool," the researchers wrote.

The interstitium could change the way doctors think about not only cancer but also potentially other diseases and many functions within the body, Theise said. 

It's the tissue around arteries that gets squeezed with every pulse of your heart, Theise said. It gets squeezed every time your bladder pushes out urine, and it's the space where tattoo pigment resides.

It's also the space where the tip of the needle goes during acupuncture, which Theise said might hold clues to how that complementary medicine approach might impact the body.

"This discovery is extremely exciting because we've defined novel microanatomy and have laid the groundwork for how this may begin to explain cancer spread, inflammation and scarring of connective tissue. This discovery will open up new research pathways for inflammation and cancer progression," said Dr. Petros Constantinos Benias, co-lead author of the study, a member of the Feinstein Institute and an assistant professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, in a written statement

"We are optimistic that with what we learned, we'll soon be able to study and target the interstitial space for diagnosis of disease and perhaps for novel personalized treatments," he said.