From organs to muscle tissue: how stem cells are being used in 3D

A Sunday Afternoon on the Island of La Grande Jatte by Georges-Pierre Seurat

When most people think of stem cells, they might conjure up an image of small dots under a microscope. It is hard to imagine these small specs being applied to three-dimensional structures. But like a pointillism painting, such as A Sunday Afternoon on the Island of La Grande Jatte by Georges-Pierre Seurat, stem cells can be used to help build things never thought possible. Two studies demonstrate this concept in very different ways.

MIT engineers have designed coiled “nanoyarn,” shown as an artist’s interpretation here. The twisted fibers are lined with living cells and may be used to repair injured muscles and tendons while maintaining their flexibility. Image by Felice Frankel

A study at MIT used nanofiber coated with muscle stem cells and mesenchymal stem cells in an effort to provide a flexible range of motion for these stem cells. Hundreds of thousands of nanofibers were twisted, resembling yarn and rope, in order to mimic the pattern found in tendons and muscle tissue throughout the body. The researchers at MIT found that the yarn like structure of the nanofibers keep the stem cells alive and growing, even as the team stretched and bent the fibers multiple times.

Normally, when a person injures these types of tissues, particularly around a major joint such as the shoulder or knee, it require surgery and weeks of limited mobility to heal properly. The MIT team hopes that their technology could be applied toward treating the site of injury while maintaining range of motion as the newly applied stem cells continue to grow to replace the injured tissue.

In an article, Dr. Ming Guo, assistant professor of mechanical engineering at MIT and one of the authors of the study, was quoted as saying,

“When you repair muscle or tendon, you really have to fix their movement for a period of time, by wearing a boot, for example. With this nanofiber yarn, the hope is, you won’t have to wearing anything like that.”

Their complete findings were published in the Proceedings of the National Academy of Sciences (PNAS).

Researchers in Germany have created transparent human organs using a new technology that could pave the way to print three-dimensional body parts such as kidneys for transplants. Above, Dr. Ali Ertuerk inspects a transparent human brain.
Photo courtesy of Reuters.

In a separate study, researchers in Germany have successfully created transparent human organs, paving the way to print three-dimensional body parts. Dr. Ali Erturk at Ludwig Maximilians University in Munich, with a team of scientists, developed a technique to create a detailed blueprint of organs, including blood vessels and every single cell in its specific location. These directions were then used to print a scaffold of the organ. With the help of a 3D printer, stem cells, acting like ink in a printer, were injected into the correct positions to make the organ functional.

Previously, 3D-printed organs lacked detailed cellular structures because they were based on crude images from computer tomography or MRI machines. This technology has now changed that.

In an article, Dr. Erturk is quoted as saying,

“We can see where every single cell is located in transparent human organs. And then we can actually replicate exactly the same, using 3D bioprinting technology to make a real functional organ. Therefore, I believe we are much closer to a real human organ for the first time now.”

Muscle stem cells provide insight into treatment of muscular dystrophies and aging muscles

Dr. Alessandra Sacco, associate professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys.

Muscles are a vital part of the body that enable us to walk, run, lift, and do everyday activities. When muscles start to deteriorate, we start to have difficulty performing these activities, which severely limits quality of life and autonomy. Typically, this becomes more commonplace as we age and is known as sarcopenia, which affects nearly ten percent of adults over the age of 50 and nearly half of individuals in their 80s.

However, there are other instances where this happens much more rapidly and early on due to genetic disease. These are commonly known as muscular dystrophies, which consist of more than 30 genetic diseases characterized by progressive muscle weakness and degeneration. A cure does not currently exist.

Regardless of the cause of the muscle deterioration, scientists at Sanford Burnham Prebys have uncovered how to potentially promote growth inside stem cells found within the muscle, thereby promoting muscle growth. In a mouse model study funded in part by CIRM and published in Nature Communications, Dr. Alessandra Sacco, senior author of the paper, and her team describe how a signaling pathway, along with a specific protein, can help regulate what muscle stem cells do.

Muscle stem cells can do two things, they either become adult muscle cells or self-renew to replenish the stem cell population. The paper discusses how the signaling pathway and specific protein are crucial for muscle stem cell differentiation and muscle growth, both of which are needed to prevent deterioration. Their aim is to use this knowledge to develop therapeutic targets that can aid with muscle growth.

Dr. Alessandra Sacco is quoted in an article as saying,

“Muscle stem cells can ‘burn out’ trying to regenerate tissue during the natural aging process or due to chronic muscle disease. We believe we have found promising drug targets that direct muscle stem cells to ‘make the right decision’ and stimulate muscle repair, potentially helping muscle tissue regeneration and maintaining tissue function in chronic conditions such as muscular dystrophy and aging.”

An unexpected link: immune cells send muscle injury signal to activate stem cell regeneration

We’ve written many blogs over the years about research focused on muscle stem cell function . Those stories describe how satellite cells, another name for muscle stem cells, lay dormant but jump into action to grow new muscle cells in response to injury and damage. And when satellite function breaks down with aging as well as with diseases like muscular dystrophy, the satellite cells drop in number and/or lose their capacity to divide, leading to muscle degeneration.

Illustration of satellite cells within muscle fibers. Image source: APSU Biology

One thing those research studies don’t focus on is the cellular and molecular signals that cause the satellite cells to say, “Hey! We need to start dividing and regenerating!” A Stanford research team examining this aspect of satellite cell function reports this week in Nature Communications that immune cells play an unexpected role in satellite cell activation. This study, funded in part by CIRM, provides a fundamental understanding of muscle regeneration and repair that could aid the development of novel treatments for muscle disorders.

ADAMTS1: a muscle injury signal?
To reach this conclusion, the research team drew upon previous studies that indicated a gene called Adamts1 was turned on more strongly in the activated satellite cells compared to the dormant satellite cells. The ADAMTS1 protein is a secreted protein so the researchers figured it’s possible it could act as a muscle injury signal that activates satellites cells. When ADAMTS1 was applied to mouse muscle fibers in a petri dish, satellite cells were indeed activated.

Next, the team examined ADAMTS1 in a mouse model of muscle injury and found the protein clearly increased within one day after muscle injury. This timing corresponds to when satellite cells drop out of there dormant state after muscle injury and begin dividing and specializing into new muscle cells. But follow up tests showed the satellite cells were not the source of ADAMTS1. Instead, a white blood cell called a macrophage appeared to be responsible for producing the protein at the site of injury. Macrophages, which literally means “big eaters”, patrol our organs and will travel to sites of injury and infection to keep them clean and healthy by gobbling up dead cells, bacteria and viruses. They also secrete various proteins to alert the rest of the immune system to join the fight against infection.

Immune cell’s double duty after muscle injury: cleaning up the mess and signaling muscle regeneration
To confirm the macrophages’ additional role as the transmitter of this ADAMTS1 muscle injury signal, the researchers generated transgenic mice whose macrophages produce abnormally high levels of ADAMTS1. The activation of satellite cells in these mice was much higher than in normal mice lacking this boost of ADAMTS1 production. And four months after birth, the increased activation led to larger muscles in the transgenic mice. In terms of muscle regeneration, one-month old transgenic mice recovered from muscle injury faster than normal mice. Stanford professor Brian Feldman, MD, PhD, the senior author of the study, described his team’s initial reaction to their findings in an interview with Scope, Stanford Medicine’s blog:

“While, in retrospect, it might make intuitive sense that the same cells that are sent into a site of injury to clean up the mess also carry the tools and signals needed to rebuild what was destroyed, it was not at all obvious how, or if, these two processes were biologically coupled. Our data show a direct link in which the clean-up crew releases a signal to launch the rebuild. This was a surprise.”

Further experiments showed that ADAMTS1 works by chopping up a protein called NOTCH that lies on the surface of satellite cells. NOTCH provides signals to the satellite cell to stay in a dormant state. So, when ADAMTS1 degrades NOTCH, the dormancy state of the satellite cells is lifted and they begin to divide and transform into muscle cells.

A pathway to novel muscle disorder therapies?
One gotcha with the ADAMTS1 injury signal is that too much activation can lead to a depletion of satellite cells. In fact, after 8 months, muscle regeneration actually weakened in the transgenic mice that were designed to persistently produce the protein. Still, this novel role of macrophages in stimulating muscle regeneration via the secreted ADAMTS1 protein opens a door for the Stanford team to explore new therapeutic approaches to treating muscle disorders:

“We are excited to learn that a single purified protein, that functions outside the cell, is sufficient to signal to muscle stem cells and stimulate them to differentiate into muscle,” says Dr. Feldman. “The simplicity of that type of signal in general and the extracellular nature of the mechanism in particular, make the pathway highly tractable to manipulation to support efforts to develop therapies that improve health.”

Have scientists discovered a natural way to boost muscle regeneration?

Painkillers like ibuprofen and aspirin are often a part of an athlete’s post-exercise regimen after intense workouts. Sore muscles, aches and stiffness can be more manageable by taking these drugs – collectively called non-steroidal anti-inflammatory drugs, or NSAIDS – to reduce inflammation and pain. But research suggests that the anti-inflammatory effects of these painkillers might cause more harm than good by preventing muscle repair and regeneration after injury or exercise.

A new study out of Stanford Medicine supports these findings and proposes that a component of the inflammatory process is necessary to promote muscle regeneration. Their study was funded in part by a CIRM grant and was published this week in the Proceedings of the National Academy of Sciences.

Muscle stem cells are scattered throughout skeletal muscle tissue and remain inactive until they are stimulated to divide. When muscles are damaged or injured, an inflammatory response involving a cascade of immune cells, molecules and growth factors activates these stem cells, prompting them to regenerate muscle tissue.

Andrew Ho, Helen Blau and Adelaida Palla led a study that found drugs like aspirin and ibuprofen can inhibit the ability of muscle tissue to repair itself in mice. (Image credit: Scott Reiff)

The Stanford team discovered that a molecule called Prostaglandin E2 or PGE2 is released during the inflammatory response and stimulates muscle repair by directly targeting the EP4 receptor on the surface of muscle stem cells. The interaction between PGE2 and EP4 causes muscle stem cells to divide and robustly regenerate muscle tissue.

Senior author on the study, Dr. Helen Blau, explained her team’s interest in PGE2-mediated muscle repair in a news release,

“Traditionally, inflammation has been considered a natural, but sometimes harmful, response to injury. But we wondered whether there might be a component in the pro-inflammatory signaling cascade that also stimulated muscle repair. We found that a single exposure to prostaglandin E2 has a profound effect on the proliferation of muscle stem cells in living animals. We postulated that we could enhance muscle regeneration by simply augmenting this natural physiological process in existing stem cells already located along the muscle fiber.”

Further studies in mice revealed that injury increased PGE2 levels in muscle tissue and increased expression of the EP4 receptor on muscle stem cells. This gave the authors the idea that treating mice with a pulse of PGE2 could stimulate their muscle stem cells to regenerate muscle tissue.

Their hunch turned out to be right. Co-first author Dr. Adelaida Palla explained,

“When we gave mice a single shot of PGE2 directly to the muscle, it robustly affected muscle regeneration and even increased strength. Conversely, if we inhibited the ability of the muscle stem cells to respond to naturally produced PGE2 by blocking the expression of EP4 or by giving them a single dose of a nonsteroidal anti-inflammatory drug to suppress PGE2 production, the acquisition of strength was impeded.”

Their research not only adds more evidence against the using NSAID painkillers like ibuprofen and aspirin to treat sore muscles, but also suggests that PGE2 could be a natural therapeutic strategy to boost muscle regeneration.

This cross-section of regenerated muscle shows muscle stem cells (red) in their niche along the muscle fibers (green). (Photo courtesy of Blau lab)

PGE2 is already approved by the US Food and Drug Administration (FDA) to induce labor in pregnant women, and Dr. Blau hopes that further research in her lab will pave the way for repurposing PGE2 to treat muscle injury and other conditions.

“Our goal has always been to find regulators of human muscle stem cells that can be useful in regenerative medicine. It might be possible to repurpose this already FDA-approved drug for use in muscle. This could be a novel way to target existing stem cells in their native environment to help people with muscle injury or trauma, or even to combat natural aging.”

Scientists find new stem cell target for regenerating aging muscles

Young Arnold (wiki)

Young Arnold (wiki)

Today I’m going to use our former governor Arnold Schwarzenegger as an example of what happens to our muscles when we age.

One of Arnold’s many talents when he was younger was being a professional bodybuilder. As you can see in this photo, Arnold worked hard to generate an impressive amount of muscle that landed him lead roles in movies Conan the Barbarian and The Terminator.

Older Arnold

Older Arnold

If you look at pictures of Arnold now (who is now 68), while still being an impressively large human being, it’s obvious that much of his muscular bulk has diminished. That’s because as humans age, so do their muscles.

Muscles shrink with age

As muscles age, they slowly lose mass and shrink (a condition called sarcopenia) because of a number of reasons – one of them being their inability to regenerate new muscle tissue efficiently. The adult stem cells responsible for muscle regeneration are called satellite cells. When muscles are injured, satellite cells are activated to divide and generate new muscle fibers that can repair injury and also improve muscle function.

However, satellite cells become less efficient at doing their job over time because of environmental and internal reasons, and scientists are looking for new targets that can restore and promote the regenerative abilities of muscle stem cells for human therapeutic applications.

A study published earlier this week in Nature Medicine, identified a potential new target that could boost muscle stem cell regeneration and improved muscle function in a mouse model of Duchenne muscular dystrophy.

β1-integrin is important for muscle regeneration

Scientists from the Carnegie Institute of Washington found that β1-integrin is important for maintaining the homeostasis (or balance) of the muscle stem cell environment. If β1-integrin is doing its job properly, muscle stem cells are able to go about their regular routine of being dormant, activating in response to injury, dividing to create new muscle tissue, and then going back to sleep.

When the scientists studied the function of β1-integrin in the muscles of aged mice, they found that the integrin wasn’t functioning properly. Without β1-integrin, mouse satellite cells spontaneously turned into muscle tissue and were unable to maintain their regenerative capacity following muscle injury.

Upon further inspection, they found that β1-integrin interacts with a growth factor called fibroblast growth factor 2 (Fgf2) and this relationship was essential for promoting muscle regeneration following injury. When β1-integrin function deteriorates as in the muscles of aged mice, the mice lose sensitivity to the regenerative capacity of Fgf2.

Restoring muscle function in mice with muscular dystrophy

By using an antibody to artificially activate β1-integrin function in the muscles of aged mice, they were able to restore Fgf2 responsiveness and boosted muscle regeneration after injury. When a similar technique was used in mice with Duchenne muscular dystrophy, they observed muscle regeneration and improved muscle function.

Muscle loss seen in muscular dystrophy mice (left). Treatment with beta1 intern boosts muscle regeneration in the same mice (right). (Nature Medicine)

Muscle loss seen in muscular dystrophy mice (left). Treatment with B1-integrin boosts muscle regeneration in the same mice (right). (Nature Medicine)

The authors believe that β1-integrin acts as a sensor of the muscle stem cell environment that it maintains a balance between a dormant and a regenerative stem cell state. They conclude in their publication:

“β1-integrin senses the SC [satellite cell] niche to maintain responsiveness to Fgf2, and this integrin represents a potential therapeutic target for pathological conditions of the muscle in which the stem cell niche is compromised.”

Co-author on the study Dr. Chen-Ming Fan also spoke to the clinical relevance of their findings in a piece by GenBio:

“Inefficient muscular healing in the elderly is a significant clinical problem and therapeutic approaches are much needed, especially given the aging population. Finding a way to target muscle stem cells could greatly improve muscle renewal in older individuals.”

Does this mean anyone can be a body builder?

So does this study mean that one day we can prevent muscle loss in the elderly and all be body builders like Arnold? I highly doubt that. It’s important to remember these are preclinical studies done in mouse models and much work needs to be done to test whether β1-integrin is an appropriate therapeutic target in humans.

However, I do think this study sheds new light on the inner workings of the muscle stem cell environment. Finding out more clues about how to promote the health and regenerative function of this environment will bring the field closer to generating new treatments for patients suffering from muscle wasting diseases like muscular dystrophy.

Stem cell stories that caught our eye: sexual identity of organs, upping the game of muscle stem cells, mini guts produce insulin

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

A new sexual identity crisis—in our organs. With the transition from Mr. to Ms. Jenner and other transsexual news this year, it seems inevitable that a research paper would come out suggesting we may all have some mosaic sexual identity. A team in the U.K. found that the stem cells that develop our organs can have varying sexual identities and that can impact the function of the organ.

The organ in question in this case, intestines in fruit flies, is smaller in males than in females. By turning on and off certain genes the researchers at the Medical Research Council’s Clinical Science Centre found that making stem cells in the gut more masculine reduced their ability to multiply and produced smaller intestines. They also found that female intestines were more prone to tumors, just as many diseases are more common in one sex than the other.

In an interview with Medical News Today, Bruno Hudry, the first author on the paper, which is published in Nature, talked about the likelihood that we all have some adult cells in us with genes of the opposite sex.

 “This study shows that there is a wider spectrum than just two sexes. You can be chromosomally, hormonally or phenotypically female but still having some specific adult stem cells (here the stem cells of the intestine) acting like male. So it is hard to say if someone is “really” male or female. Some people are simply a mosaic of male and female cells within a phenotypically ‘male’ or ‘female’ body.”

Hurdry speculated that if the results are duplicated in humans it could provide a window into other sex-linked differences in diseases and could be a matching factor added to the standard protocol for blood and organ donations.

 

Reprogramming stomach to produce insulin.  The stem cells in our gut show an efficiency not seen in most of our organs. They produce a new lining for our stomach and intestine every few days. On the opposite end of the spectrum, the insulin-producing cells in our pancreas rank poorly in self renewal. So, what if you could get some of those vigorous gut stem cells to make insulin producing beta cells? Turns out you can and they can produce enough insulin to allow a diabetic mouse to survive.

mini stomach

A mini-gut with insulin-producing cells (red) and stem cells (green).

A team at the Harvard Stem Cell Institute manipulated three genes known to be associated with beta cell development and tested the ability of many different tissues—from tail to snout—to produce beta cells. A portion of the stomach near the intestine, which naturally produces other hormones, easily reprogrammed into insulin producing cells. More important, if the first batch of those cells was destroyed by the team, the remaining stem cells in the tissue quickly regenerated more beta cells. Since a misbehaving immune system causes type 1 diabetes, this renewal ability could be key to preventing a return of the disease after a transplant of these cells.

In the lab the researchers pushed the tissue from the pylorous region of the stomach to self-organize into mini-stomachs along with the three genetic factors that drive beta cell production.  When transplanted under the skin of mice that had previously had their beta cells destroyed, the mice survived. The genetic manipulations used in this research could not be used in people, but the team is working on a system that could.

 “What is potentially really great about this approach is that one can biopsy from an individual person, grow the cells in vitro and reprogram them to beta cells, and then transplant them to create a patient-specific therapy,” said Qiao Zhou, the senior author. “That’s what we’re working on now. We’re very excited.”

Medicalxpress ran a story about the work published in Cell Stem Cell.

 

muscle stem cells

Muscle stem cells generate new muscle (green) in a mouse.

Better way to build muscle.  Stem cells behave differently depending on what environment they find themselves in, but they are not passive about their environment. They can actively change it. A CIRM-funded team at Sanford Burnham Prebys Medical Discovery Institute (SBP) found that fetal muscle stem cells and adult muscle stem cells make very different changes in the micro-environment around them.

Fetal muscle stem cells become very good at generating large quantities of new muscle, while the adult stem cells take the role of maintaining themselves for emergencies. As a result, when major repair is needed like in muscular dystrophies and aging, they easily get overwhelmed. So the SBP team looked for ways to make the adult stem cells behave more like their fetal predecessors.

 “We found that fetal MuSCs remodel their microenvironment by secreting specific proteins, and then examined whether that same microenvironment can encourage adult MuSCs to more efficiently generate new muscle. It does, which means that how adult MuSCs normally support muscle growth is not an intrinsic characteristic, but can be changed,” said Matthew Tierney, first author of the study in an institute press release distributed by Newswise.

The results point to paths for developing therapies for a number of muscle wasting conditions.

Researchers cool to idea of ice bath after exercise

Have you ever had a great workout, really pushed your body and muscles hard and thought “You know what would be good right now? A nice plunge into an ice bath.”

No. Me neither.

Weightlifter Karyn Marshall taking an ice bath: Photo courtesy Karyn Marshall

Weightlifter Karyn Marshall taking an ice bath: Photo courtesy Karyn Marshall

But some people apparently believe that taking an ice bath after a hard workout can help their muscles rebound and get stronger.

It’s a mistaken belief, at least according to a new study from researchers at the Queensland University of Technology (QUT) and the University of Queensland (UQ) in Australia. They are – pardon the pun – giving the cold shoulder to the idea that an ice bath can help hot muscles recover after a hard session of strength training.

The researchers got 21 men who exercise a lot to do strength training twice a week for 12 weeks. One group then agreed – and I’d love to know how they persuaded them to do this – to end the training session by jumping into a 50 degrees Fahrenheit (10 Celsius) ice bath. The other group – let’s label them the “sensible brigade” – ended by doing their cool down on an exercise bike.

Happily for the rest of us at the end of the 12 weeks the “sensible brigade” experienced more gains in muscle strength and muscle mass than the cool kids.

So what does this have to do with stem cells? Well the researchers say the reason for this result is because our bodies use so-called satellite cells – which are a kind of muscle stem cell – to help build stronger muscles. When you plunge those muscles into a cold bath you effectively blunt or block the ability of the muscle stem cells to work as well as they normally would.

But the researchers weren’t satisfied just putting that particular theory on ice, so in a second study they took muscle biopsies from men after they had done leg-strengthening exercises. Again, half did an active cool down, the others jumped in the ice bath.

In a news release accompanying the article in the The Journal of Physiology, Dr Llion Roberts, from UQ’s School of Human Movement and Nutrition Sciences, said the results were the same:

“We found that cold water immersion after training substantially attenuated, or reduced, long-term gains in muscle mass and strength. It is anticipated that athletes who use ice baths after workouts would see less long-term muscle gains than those who choose an active warm down.”

The bottom line; if you strain a muscle working out ice is your friend because it’s great for reducing inflammation. If you want to build stronger muscles ice is not your friend. Save it for that nice refreshing beverage you have earned after the workout.

Cheers!

CIRM-Funded Scientists Test Recipe for Building New Muscles

When muscles get damaged due to disease or injury, the body activates its reserves—muscle stem cells that head to the injury site and mature into fully functioning muscle cells. But when the reserves are all used up, things get tricky.

Scientists at Sanford-Burnham may have uncovered the key to muscle repair.

Scientists at Sanford-Burnham may have uncovered the key to muscle repair.

This is especially the case for people living with muscle diseases, such as muscular dystrophy, in which the muscle degrades at a far faster rate than average and the body’s reserve stem cell supply becomes exhausted. With no more supply from which to draw new muscle cells, the muscles degrade further, resulting in the disease’s debilitating symptoms, such as progressive difficulty walking, running or speaking.

So, scientists have long tried to find a way to replenish the dwindling supply of muscle stem cells (called ‘satellite cells’), thus slowing—or even halting—muscle decay.

And now, researchers at the Sanford-Burnham Medical Research Institute have found a way to tweak the normal cycle, and boost the production of muscle cells even when supplies appear to be diminished. These findings, reported in the latest issue of Nature Medicine, offer an alternative treatment for the millions of people suffering not only from muscular dystrophy, but also other diseases that result in muscle decay—such as some forms of cancer and age-related diseases.

In this study, Sanford-Burnham researchers found that introducing a particular protein, called a STAT3 inhibitor, into the cycle of muscle-cell regeneration could boost the production of muscle cells—even after multiple rounds of repair that would otherwise render regeneration virtually impossible.

The STAT3 inhibitor, as its name suggests, works by ‘inhibiting,’ or effectively neutralizing, another protein called STAT3. Normally, STAT3 gets switched on in response to muscle injury, setting in motion a series of steps that replenishes muscle cells.

In experiments first in animal models of muscular dystrophy—and next in human cells in a petri dish—the team decided to modify how STAT3 functions. Instead of keeping STAT3 active, as would normally occur, the team introduced the STAT3 inhibitor at specific times during the muscle regeneration process. And in so doing, noticed a significant boost in muscle cell production. As Dr. Alessandra Sacco, the study’s senior author, stated in a news release:

“We’ve discovered that by timing the inhibition of STAT3—like an ‘on/off’ light switch—we can transiently expand the satellite cell population followed by their differentiation into mature cells.”

This approach to spurring muscle regeneration, which was funded in part by a CIRM training grant, is not only innovative, but offers new hope to a disease for which treatments have offered little. As Dr. Vittorio Sartorelli, deputy scientific director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), stated:

“Currently, there is no cure to stop or reverse any form of muscle-wasting disorders—only medication and therapy that can slow the process. A treatment approach consisting of cyclic bursts of STAT3 inhibitors could potentially restore muscle mass and function in patients, and this would be a very significant breakthrough.”

Sacco and her colleagues are encouraged by these results, and plan to explore their findings in greater detail—hopefully moving towards clinical trials:

“Our next step is to see how long we can extend the cycling pattern, and test some of the STAT3 inhibitors currently in clinical trials for other indications such as cancer, as this could accelerate testing in humans.”