Tag Archives: biomedicine

Scaffolding

If stem cells don’t grow as you want them to, just add a dash of parsley-husk scaffolding

University of Wisconsin-Madison researchers are investigating de-cellularized plant husks as potential 3D scaffolds which, when seeded with human stem cells, could lead to a new class of biomedical implants and tailored tissues.

Scaffolding

Image via Pixabay.

We may like to call ourselves the superior being or top of the food chain and all that, but as far as design elegance and functionality is concerned, the things nature comes up with make us look like amateurs. Luckily, we’re not above emulating/copying/appropriating these designs, meaning that structures created by plants and animals have long and liberally been used to advance science and technology.

Joining this noblest of scientific traditions, UWM scientists have turned to de-celled husks of plants such as parsley, vanilla, or orchids to create 3D scaffolds which can be seeded with human stem cells and optimized for growth in lab cultures. This approach would provide an inexpensive, easily scalable and green technology for creating tiny structures which can be used to repair bits of our bodies using stem cells.

Plantfolding

The technology draws on the natural qualities of plant structures — strength, porosity, low weight, all coupled with large surface-to-volume ratios — to overcome several of the limitations current scaffolding methods, such as 3D printing or injection molding, face in creating efficient feedstock structures for biomedical applications.

“Nature provides us with a tremendous reservoir of structures in plants,” explains Gianluca Fontana, lead author of the new study and a UW-Madison postdoctoral fellow. “You can pick the structure you want.”

“Plants are really special materials as they have a very high surface area to volume ratio, and their pore structure is uniquely well-designed for fluid transport,” says William Murphy, professor of biomedical engineering and co-director of the UW-Madison Stem Cell and Regenerative Medicine Center, who coordinated the team’s efforts.

The team worked together with Madison’s Olbrich Botanical Gardens’ staff and curator John Wirth to identify which species of plants could be used for the tiny scaffolds. In addition to parsley and orchids, the garden’s staff also found that bamboo, elephant ear plants, and wasabi have structures that would be useful in bioengineering for their shape or other properties. Bulrush was also found to hold promise following examinations of plants in the UW Arboretum.

Human fibroblast cells growing on decellularized parsley.
Image credits Gianluca Fontana / UW-Madison.

Plants form such good scaffolds because their cellular walls are rich in cellulose — probably the most abundant polymer on Earth, as plants use it to form a rough equivalent of our skeleton. The UWM team found that if they strip away all the plant’s cells and chemically treat the left-over cellulose, human stem cells such as fibroblasts are very eager to take up residence in the husks.

Even better, the team observed that stem cells seeded into the scaffolds tended to align to the scaffold’s structure. So it should be possible to use these plant husks to control the structure and alignment of developing human tissues, Murphy says, a critical achievement for muscle or nerve tissues — which don’t work unless correctly aligned and patterned. Since there’s a huge variety of plants — with unique cellulose structures — in nature, we can simply find one that suits our need and use that to tailor the tissues we want.

“Stem cells are sensitive to topography. It influences how cells grow and how well they grow,” Fontana added.

“The vast diversity in the plant kingdom provides virtually any size and shape of interest,” notes Murphy. “It really seemed obvious. Plants are extraordinarily good at cultivating new tissues and organs, and there are thousands of different plant species readily available. They represent a tremendous feedstock of new materials for tissue engineering applications.”

Another big plus for the plantfolds is how easy they are to produce and work with, being “quite pliable […] easily cut, fashioned, rolled or stacked to form a range of different sizes and shapes,” according to Murphy. They’re also easy and cheap to mass produce as well as renewable on account of being, you know, plants.

So far, these scaffolds seem to hold a huge potential. They’ve yet to be tested in living organisms, but there are plans to do so in the future.

The scaffolds have yet to be tested in an animal model, but plans are underway to conduct such studies in the near future.

“Toxicity is unlikely, but there is potential for immune responses if these plant scaffolds are implanted into a mammal,” says Murphy.

“Significant immune responses are less likely in our approach because the plant cells are removed from the scaffolds.”

The full paper “Biomanufacturing Seamless Tubular and Hollow Collagen Scaffolds with Unique Design Features and Biomechanical Properties” has been published in the journal Advanced Healthcare Materials.

Discarded Thymus glands offer new hope for people with autoimmune disease

The thymus is one of those under appreciated organs you just don’t hear much about. Sitting in your chest, just in front of your heart, the thymus is at its largest and most active during infancy and childhood. By adulthood, the thymus has shrunk to practically nothing, being mostly replaced by fat. It plays an important role in the health of your immune system, and is the location where certain immune cells, called T-cells, go to mature and develop properly.

The thymus is like a schoolhouse for T-cells where they learn important lessons, like “recognize these sets of proteins as part of our own body and don’t attack them, but attack anything you don’t recognize because it must be a foreign intruder”. It allows the immune system to develop what is known as Central Tolerance. Without central tolerance, we develop auto-immune disease, which is essentially your immune system fighting a civil war against other parts of your own body. Diseases like Lupus, Type 1 diabetes, Myasthenia gravis, and many others are autoimmune diseases with the immune system actively damaging some parts of the body. In Type 1 diabetes, for instance, the immune system targets your pancreatic islet cells for destruction, resulting in loss of your bodies ability to make insulin.

 

The thymus is an organ where T-cells mature, and may be a source of regulatory T-cells that have the potential to treat autoimmune disease.

The thymus is an organ where T-cells mature, and may be a source of regulatory T-cells that have the potential to treat autoimmune disease.

 

It is also known that there are many varieties of T-cells, each with unique and important roles to play in immune function. One type of T-cell is known as the Regulatory T-cell or Treg. Tregs are special because they help to keep the other cells of the immune system from getting too wild and out of control (a recipe for autoimmune disease). They can go into an inflammatory situation where lots of immune cells are activated and ready to rumble, and tell those cells, “alright, everyone just calm down”, thereby suppressing the immune response. Some studies have show that Tregs can be infused into patients with autoimmune disease to help control their symptoms. They might even be a valuable way to suppress the immune system in people with an organ transplant, like a kidney or heart. Tregs are a way to use one part of the immune system to control other parts of the immune system – like fighting fire with fire – in the case of autoimmune disease.

These treatments, while promising, are still not fully evaluated and are not standard of care as of yet. One reason that not much research has been done using Tregs as a therapy is that they are hard to come by. They can be collected from the blood of donors, then grown in the lab to try to get enough cells for treatment, but the process is inefficient and doesn’t result in a large number of Treg cells.

This month in the American Journal of Transplantation, a team of Canadian researcher showed that discarded human thymuses are an excellent source of Tregs that can be harvested and used to treat a variety of immune mediated disease. So why would there ever be a discarded thymus? It turns out that when an infant is undergoing heart surgery, as might be done to correct a cardiac birth defect, the thymus is huge and in the surgeons’ way, and must be removed to gain access to the heart. This is true in infants where the thymus is very large compared to the heart, but not a problem in adults where the thymus has already atrophied to a tiny insignificant size.

Tregs can be identified and isolated based on unique protein markers on their cell surfaces such as CD25+,CD4+, and FOXP3. Other immune cells show different sets of markers making it possible to identify the different cell types, and select only the ones needed. The researchers found that they could identify and isolate many more Tregs from one discarded infant thymus, than could be generated from the blood of an adult donor. In fact, they could show that there are more Tregs in an infant thymus than are present in the entire circulation of an adult. They also found that the Tregs from discarded infant thymus function better compared to those recovered from the process of blood donation. It is thought that this might be due to the immaturity of Tregs coming from thymus versus blood, since those in the blood have been around longer and show other markers of cellular aging, such as shorter telomere length.

Perhaps if more Tregs become available from thymus harvesting, more clinical studies studies will be conducted that may hopefully find effective ways to treat autoimmune diseases that today are very difficult to control and create much suffering in the lives of so many people.

 

Reference Article:
1. Am J Transplant. 2016 Jan;16(1):58-71. doi: 10.1111/ajt.13456. Epub 2015 Sep 28.  Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells.
Dijke IE1,2, Hoeppli RE3, Ellis T1,2, Pearcey J1,2, Huang Q3, McMurchy AN3, Boer K4, Peeters AM4, Aubert G5, Larsen I1,2, Ross DB2,6, Rebeyka I2,6, Campbell A3, Baan CC4, Levings MK3, West LJ1,2,6.

The sea lamprey, a very simple organism which dwells in the Atlantic waters, which scientists will use as inspiration for a bio-mechanical device capable of traveling through your body. Not that much of looker, but he's on our side. (c) U.S. Fish and Wildlife Service.

Bio-mechanical hybrid robot might detect diseases from inside your body

Scientists at Newcastle University are currently developing a tiny bio-inspired robot, just one centimeter in length, which in less than five years might be used to diagnose and pinpoint diseases from inside the human body.

The sea lamprey, a very simple organism which dwells in the Atlantic waters, which scientists will use as inspiration for a bio-mechanical device capable of traveling through your body. Not that much of looker, but he's on our side. (c)  U.S. Fish and Wildlife Service.

The sea lamprey, a very simple organism which dwells in the Atlantic waters, which scientists will use as inspiration for a bio-mechanical device capable of traveling through your body. Not that much of looker, but he's on our side. (c) U.S. Fish and Wildlife Service.

The researchers, backed-up by the American National Science Foundation and the UK’s Engineering and Physical Sciences Research Council,  are hoping to succeed where other scientists at nano labs across the world have been painstakingly trying to achieve as well – a working, safe tiny device which can swim through the blood stream and collect critical information, irretrievable otherwise.

Called the “Cyberplasm”, the Newcastle scientists’ take involvesa  biomimicking robot that functions like a living creature loaded with sensors derived from animal cells, inspired by the  sea lamprey, a creature found mainly in the Atlantic Ocean. The animal has an extremely nervous system, making it perfect for bio-mechanical mimicking.

“Nothing matches a living creature’s natural ability to see and smell its environment and therefore to collect data on what’s going on around it,” Dr Frankel noted.

Cyberplasm will have an electronic nervous system, ‘eye’ and ‘nose’ sensors derived from mammalian cells, and artificial muscles that use glucose as an energy source. Its sensors are being developed to respond to external stimuli, like chemical signals or light, much in the same way organisms do in nature by converting them into electronic impulses that are sent to an electronic ‘brain’ equipped with sophisticated microchips. This information will be then used by the brain to send electronic messages to artificial muscles, telling them to contract or relax, resulting in an undulating motion which propels the Cyberplasm and allows it to navigate through the human body. Data on the chemical make-up of the robot’s surroundings can be collected and stored for later recovery, information later used for diagnosis.

Besides disease diagnosis, the researchers believe the Cyberplasm might have some immediate applications in the prosthetics sector, where the tiny bio-robot might be used to stimulate  living muscle tissue to contract and relax.  The researchers are currently developing the components of Cyberplasm individually, and while the initial prototype will be one centimeter long, they’re confident they can scale it down to nano-size in time – a working device should be ready within five years.

“We’re currently developing and testing Cyberplasm’s individual components,” Frankel concluded. “We hope to get to the assembly stage within a couple of years. We believe Cyberplasm could start being used in real world situations within five years”.

University of Newcastle  / Eureka Alert

NIH Grants drastically rolled back by federal budget cuts

As if it wasn’t enough NIH funded grant applications are at a 20% low, according to a proposed federal discretionary civilian spending cut plan back to 2008 levels, biomedical researcher funds could drop by half, to a historical low of 10%.  National Institutes of Health (NIH) Director Francis Collins spoke in detail about the issue during his keynote speech during an annual meeting of the  American Society of Human Genetics. “There are certainly concerns, especially with some of the rhetoric you’ve heard since Tuesday,” when midterm elections took place, Collins said.

What might probably happen? Well for sure a significant number of labs will close down, unmotivated researchers and future talent left unfunded (today, approx. one in five grant applications get accepted – expect the ratio to get at least two times thinner). Why? Because of the Republicans’ vow to cut discretionary civilian spending, as if a nation’s deficit stands in progress and not in another economical sectors, like manufacturing and production. If you’re hungry, you don’t buy a fish, you learn to fish.

Let’s hope for the best as we wait for more news from the NIH.

Source: Science Mag