Meet your interstitium

Using a new way of visualising anatomy, scientists in the US have just discovered a vast new structure in the human body that could be considered an organ in its own right.

The finding, published in the journal Scientific Reports, has important implications for our understanding of how all organs and tissues function, and could reveal previously unknown mechanisms driving diseases such as fibrosis and cancer.

But how could something so significant have gone unnoticed all this time?

It was well known that a layer of tissue lies just below the surface of the skin, and also lines the lungs, the digestive and urinary tracts, and much of the circulatory system. But it was thought this comprised little more than dense, connective tissue.

The new research reveals that it is actually a vast, interconnected system of fluid-filled compartments that extends all over the body.

That contents is extra-cellular, or “interstitial”, fluid. Accordingly, the structure has been dubbed “the interstitium”.

Until now, the interstitium had been hidden in plain sight because the traditional method of preparing microscope slides involves draining away fluid. This had caused the sacs to collapse, leaving only the supportive connective tissue visible.

But recently, researchers led by Neil Theise at New York University in the US began using probe-based confocal laser endomicroscopy, which aims laser light at living tissue and detects reflected fluorescent patterns, providing a different sort of microscopic image. While examining the bile duct of a cancer patient, they found a network of fluid-filled sacks that had never been seen before.

They soon found this network everywhere tissues are distended or compressed as part of normal function — which is quite a lot of the body — and propose that the interstitium may function as a shock absorber.

Its physical structure is certainly quite unusual: the fluid-filled spaces are supported by an extensive lattice of collagen bundles that are lined on only one side by what appear to be a type of stem cell.

These cells may help make collagen, and could aid in wound healing. Similarly, they could contribute to conditions associated with inflammation and ageing.

In addition to cushioning, the interstitium may have another important job. While it was known that interstitial fluid is the major source of lymph fluid, which carries immune cells throughout the body, just how it reaches the lymphatic system was unclear. The new research shows that the interstitium drains directly into the lymph nodes.

The study also shows that cancers, such as melanoma, are able to spread via the interstitium.

“This finding has potential to drive dramatic advances in medicine, including the possibility that the direct sampling of interstitial fluid may become a powerful diagnostic tool,” says Theise.