Tag Archives: mesh

Meet your new organ: the interstitium

Doctors have identified a previously unknown feature of human anatomy with many implications for the functions of most organs and tissues, and for the mechanisms of most major diseases.

Structural evaluation of the interstitial space. (A) Transmission electron microscopy shows collagen bundles (asterisks) that are composed of well-organized collagen fibrils. Some collagen bundles have a single flat cell along one side (arrowheads). Scale bar, 1 μm. (B) Higher magnification shows that cells (arrowhead) lack features of endothelium or other types of cells and have no basement membrane. Scale bar, 1 μm. (C) Second harmonics generation imaging shows that the bundles are fibrillar collagen (dark blue). Cyan-colored fibers are from autofluorescence and are likely elastin, as shown by similar autofluorescence in the elastic lamina of a nearby artery (inset) (40×). (D) Elastic van Gieson stain shows elastin fibers (black) running along collagen bundles (pink) (40×).

A new paper published on March 27th in Scientific Reports, shows that layers of the body long thought to be dense, connective tissues — below the skin’s surface, lining the digestive tract, lungs, and urinary systems, and surrounding arteries, veins, and the fascia between muscles — are instead interconnected, fluid-filled spaces.

Scientists named this layer the interstitium — a network of strong (collagen) and flexible (elastin) connective tissue fibers filled with fluids, that acts like a shock absorber to keep tissues from rupturing while organs, muscles, and vessels constantly pump and squeeze throughout the day.

This fluid layer that surrounds most organs may explain why cancer spreads so easily. Scientists think this fluid is the source of lymph, the highway of the immune system.

In addition, cells that reside in the interstitium and collagen bundles they line, change with age and may contribute to the wrinkling of skin, the stiffening of limbs, and the progression of fibrotic, sclerotic and inflammatory diseases.

Scientists have long known that more than half the fluid in the body resides within cells, and about a seventh inside the heart, blood vessels, lymph nodes, and lymph vessels. The remaining fluid is “interstitial,” and the current paper is the first to define the interstitium as an organ in its own right and, the authors write, one of the largest of the body, the authors write.

A team of pathologists from NYU School of Medicine thinks that no one saw these spaces before because of the medical field’s dependence on the examination of fixed tissue on microscope slides. Doctors examine the tissue after treating it with chemicals, slicing it thinly, and dyeing it in various colorations. The “fixing” process allows doctors to observe vivid details of cells and structures but drains away all fluid. The team found that the removal of fluid as slides are made makes the connective protein meshwork surrounding once fluid-filled compartments to collapse and appear denser.

“This fixation artifact of collapse has made a fluid-filled tissue type throughout the body appear solid in biopsy slides for decades, and our results correct for this to expand the anatomy of most tissues,” says co-senior author Neil Theise, MD, professor in the Department of Pathology at NYU Langone Health. “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.”

Researchers discovered the interstitium by using a novel medical technology — Probe-based confocal laser endomicroscopy. This new technology combines the benefits of endoscopy with the ones of lasers. The laser lights up the tissues, sensors analyze the reflected fluorescent patterns, offering a microscopic real-time view of the living tissues.

When probing a patient’s bile duct for cancer spread, endoscopists and study co-authors Dr. David Carr-Locke and Dr. Petros Benias observed something peculiar — a series of interconnected spaces in the submucosa level that was never described in the medical literature.

Baffled by their findings, they asked Dr. Neil Theise, professor in the Department of Pathology at NYU Langone Health and co-author of the paper for help in resolving the mystery. When Theise made biopsy slides out of the same tissue, the reticular pattern found by endomicroscopy vanished. The pathology team would later discover that the spaces seen in biopsy slides, traditionally dismissed as tears in the tissue, were instead the remnants of collapsed, previously fluid-filled, compartments.

Researchers collected tissues samples of bile ducts from 12 cancer patients during surgery. Before the pancreas and the bile duct were removed, patients underwent confocal microscopy for live tissue imaging. After recognizing this new space in images of bile ducts, the team was able to quickly spot it throughout the body.

Theise believes that the protein bundles seen in the space are likely to generate electrical current as they bend with the movements of organs and muscles, and may play a role in techniques like acupuncture.

Another scientist involved in the study was first author Rebecca Wells of the Perelman School of Medicine at the University of Pennsylvania, who determined that the skeleton in the newfound structure was comprised of collagen and elastin bundles.

Scientists create neural lace that fuses with your brain

In a world where in only a few decades we went from clunky phones to wireless satellite-connected devices that allow us to be anywhere and do anything on the internet, it seems only normal that scientists will take it to the next level – to your brain. Already tested on mice, this fine mesh fits inside a syringe and unfurls on the brain to monitor its activity, creating a bio-technological interface which could revolutionize medicine.

The rolled electronic mesh is injected through a glass needle into a water-based solution. (Lieber Research Group, Harvard University)

A group of chemists and engineers who work with nanotechnology published a paper in Nature Nanotechnology where they describe a new ultra-fine mesh they’ve developed that merges with the brain and creates a machine-biological functionality. For now, the mice with this electronic mesh are connected by a wire to computer — but in the future, this connection could become wireless.

“We’re trying to blur the distinction between electronic circuits and neural circuits,” says Charles Lieber, a nanotechnologist at Harvard University and co-author of a study describing the device this week in Nature Nanotechnology.

Called “mesh electronics,” the device is so thin that it can be directly injected to the brain, where it attaches to the brain. The technology was already successfully tested on mice, who not only survived the implantation, but seem to have no negative side effects. This could have a lot of potential applications, including monitoring brain activity and delivering treatment for degenerative diseases such as Parkinson’s. It might even be used to artificially boost brain capacity.

A 3-D microscope image shows the mesh injected into a region of the brain called the lateral ventricle. (Lieber Research Group, Harvard University)

“This could make some inroads to a brain interface for consumers,” says Jacob Robinson, who develops technologies that interface with the brain at Rice University. “Plugging your computer into your brain becomes a lot more palatable if all you need to do is inject something.”

The mesh also gives scientists access to previously inaccessible areas of the brain; when researchers want to study some areas of the brain of a mouse, they have to actually cut a piece from it, but this technology might change that, allowing remote research. Further down the line, delivering treatment directly to the brain could be the way to go.

It might surprise you to learn that neural electronics are already a reality for some people. Patients suffering from severe epilepsy or tremors can find relief via electric shocks, which are delivered by long wires threaded deep into the brain. Also, quadriplegics have learned to control prosthetic limbs using chips embedded in the brain. But we’re still pretty far away from actually implementing the mesh in humans. For starters, researchers need to ensure a longer mesh lifespan. Previous neural meshes have suffered from stability problems either with the signal they output or their own structure. But the team is optimistic that this time, the mesh will blend in with the brain and quietly fit in the empty gaps.

“We have to walk before we can run, but we think we can really revolutionize our ability to interface with the brain,” says Lieber.

Journal Reference: Jia Liu, Tian-Ming Fu, Zengguang Cheng, Guosong Hong, Tao Zhou, Lihua Jin, Madhavi Duvvuri, Zhe Jiang, Peter Kruskal, Chong Xie, Zhigang Suo, Ying Fang & Charles M. Lieber. Syringe-injectable electronics. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.115