Harder, Better, Faster, Stronger: Scientists Work to Create Improved Immune System One Cell at a Time

The human immune system is the body’s best defense against invaders. But even our hardy immune systems can sometimes be outpaced by particularly dangerous bacteria, viruses or other pathogens, or even by cancer.

Salk Institute scientists have developed a new cellular reprogramming technique that could one day boost a weakened immune system.

Salk Institute scientists have developed a new cellular reprogramming technique that could one day boost a weakened immune system.

But what if we could give our immune system a boost when it needs it most? Last week scientists at the Salk Institute for Biological Sciences devised a new method of doing just that.

Reporting in the latest issue of the journal Stem Cells, Dr. Juan Carlos Izpisua Belmonte and his team announce a new method of creating—and then transplanting—white blood cells into laboratory mice. This new and improved method could have significant ramifications for how doctors attack the most relentless disease.

The authors achieved this transformation through the reprogramming of skin cells into white blood cells. This process builds on induced pluripotent stem cell, or iPS cell, technology, in which the introduction of a set of genes can effectively turn one cell type into another.

This Nobel prize-winning approach, while revolutionary, is still a many months’ long process. In this study, the Salk team found a way to shorten the cellular ‘reprogramming’ process from several months to just a few weeks.

“The process is quick and safe in mice,” said Izpisua Belmonte in a news release. “It circumvents long-standing obstacles that have plagued the reprogramming of human cells for therapeutic and regenerative purposes.”

Traditional reprogramming methods change one cell type, such as a skin cell, into a different cell type by first taking them back into a stem cell-like, or ‘pluripotent’ state. But here, the research team didn’t take the cells all the way back to pluripotency. Instead, they simply wiped the cell’s memory—and gave it a new one. As first author Dr. Ignacio Sancho-Martinez explained:

“We tell skin cells to forget what they are and become what we tell them to be—in this case, white blood cells. Only two biological molecules are needed to induce such cellular memory loss and to direct a new cell fate.”

This technique, which they dubbed ‘indirect lineage conversion,’ uses the molecule SOX2 to wipe the skin cell’s memory. They then use another molecule called miRNA 125b to reprogram the cell into a white blood cell.

These newly generated cells appear to engraft far better than cells derived from traditional iPS cell technology, opening the door to therapies that more effectively introduce these immune cells into the human body. As Sanchi-Martinez so eloquently stated:

“It is fair to say that the promise of stem cell transplantation is now closer to realization.”

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.”

Stem Cell Stories that Caught our Eye: What’s the Best Way to Treat Deadly Cancer, Destroying Red Blood Cells’ Barricade, Profile of CIRM Scientist Denis Evseenko

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.

Stem Cells vs. Drugs for Treating Deadly Cancer. When dealing with a potentially deadly form of cancer, choosing the right treatment is critical. But what if that treatment also poses risks, especially for older patients? Could advances in drug development render risky treatments, such as transplants, obsolete?

That was the focus of a pair of studies published this week in the New England Journal of Medicine, where a joint Israeli-Italian research team investigated the comparative benefits of two different treatments for a form of cancer called multiple myeloma.

Multiple myeloma attacks the body’s white blood cells. While rare, it is one of the most deadly forms of cancer—more than half of those diagnosed with the disease do not survive five years after being diagnosed. The standard form of treatment is usually a stem cell transplant, but with newer and better drugs coming on the market, could they render transplants unnecessary?

In the twin studies, the research team divided multiple myeloma patients into two groups. One received a combination of stem cell transplant and chemotherapy, while the other received a combination of drugs including melphalan, prednisone and lenalidmomide. After tracking these patients over a period of four years, the research team saw a clear advantage for those patients that had received the transplant-chemotherapy treatment combination.

To read more about these twin studies check out recent coverage in NewsMaxHealth.

Breaking Blood Cells’ Barricade. The process whereby stem cells mature into red blood cells is, unfortunately, not as fast as scientists would like. In fact, there is a naturally occurring barrier that keeps the production relatively slow. In a healthy person this is not necessarily a problem, but for someone in desperate need of red blood cells—it can prove to be very dangerous.

Luckily, scientists at the University of Wisconsin-Madison have found a way to break through this barrier by switching off two key proteins. Once firmly in the ‘off’ position, the team could boost the production of red blood cells.

These findings, published in the journal Blood, are critical in the context of disease anemia, where the patient’s red blood cell count is low. They also may lead to easier methods of stocking blood banks.

Read more about this exciting discovery at HealthCanal.

CIRM Scientist on the Front Lines of Cancer. Finally, HealthCanal has an enlightening profile of Dr. Denis Evseenko, a stem cell scientist and CIRM grantee from the University of California, Los Angeles (UCLA).

Born in Russia, the profile highlights Evseenko’s passion for studying embryonic stem cells—and their potential for curing currently incurable diseases. As he explains in the article:

“I had a noble vision to develop progressive therapies for the patient. It was a very practical vision too, because I realized how limited therapeutic opportunities could be for the basic scientist, and I had seen many great potential discoveries die out before they ever reached the clinic. Could I help to create the bridge between stem cells, research and actual therapeutics?”

Upon arriving at UCLA, Evseenko knew he wanted to focus this passion into the study of degenerative diseases and diseases related to aging, such as cancer. His bold vision of bridging the gap between basic and translational research has earned him support not only from CIRM, but also the National Institutes of Health and the US Department of Defense, among others. Says Evseenko:

“It’s my hope that we can translate the research we do and discoveries we make here to the clinic to directly impact patient care.”

Throwback Thursday: Scientists Create Synthetic Version of Earth’s Earliest Primordial Cells

Cells as we know them today—no matter the species—are feats of evolution; molecular machines with thousands of interlocking parts. But they didn’t start out that way.

Scientists have built a simplified cell membrane that mimics natural cellular processes and movements.

Scientists have built a simplified cell membrane that mimics natural cellular processes and movements.

Using the latest tools from the new field of synthetic biology, a team of biophysicists from Tecnische Universitaet Muenchen (TUM) in Munich, Germany, has constructed a synthetic version of an early cell, complete with some biomechanical function.

To build a primordial cell, the recipe is simple: all you need is a membrane shell, a couple of biomolecules that perform the most basic of functions, and some fuel to keep it going.

Here, TUM researchers used lipids (fat molecules) to create a double-layer cellular membrane that mimics a cell’s natural membrane. They then filled the membrane with microtubules, which acted as cellular ‘scaffolding’ to hold everything in place, and another molecule called ‘kinesin.’ These kinesin molecules serve as molecular ‘motors,’ transporting components throughout the cell by traveling along the microtubule scaffolding. Finally, they added the fuel: a compound called adenosine triphosphate, or ATP. The scientists likened this set-up to a liquid crystal layer within the membrane that is in a permanent state of motion. As lead author Felix Keber explained in a news release:

“One can picture the liquid crystal layer as tree logs drifting on the surface of a lake. When it becomes too congested, they line up in parallel but can still drift alongside each other.”

Once constructed, the research team then wanted to understand how these synthetic cells behaved, and if it would mimic natural cellular movements. And much to the team’s surprise—they did.

During a process called osmosis—where water droplets selectively pass through the membrane—the researchers noticed a change in the cells’ shape as water left the interior of the cell. The resulting membrane slack was causing the microtubules to stick out like spikes. These ‘spiked extensions’ were eerily similar to what the extensions that scientists have seen cells normally use to get around.

This observation cleared up a long-standing mystery: the way cells change shape and move around wasn’t random. The cells were simply following the basic laws of physics. This discovery then led the team to uncover the underlying mechanisms of other cellular behaviors—and even make predictions on other systems.

As the study’s lead author, Professor Andreas Bausch, stated in the same release:

“With our synthetic biomolecular model we have created a novel option for developing minimal cell models. It is ideally suited to increasing the complexity in a modular fashion in order to reconstruct cellular processes like cell migration or cell division in a controlled manner.”

In the future, the team hopes to build this knowledge to a point where they can understand the physical basis for deformed cells—with potential applications to disease modeling. Bausch added:

“That the artificially created system can be comprehensively described from a physical perspective gives us hope that in the next steps we will also be able to uncover the basic principles behind the manifold cell deformations.”

Body’s own Healing Powers Could be Harnessed to Regrow Muscle, Wake Forest Study Finds

Imagine being able to repair muscle that had been damaged in an injury, not by transplanting new muscle or even by transplanting cells, but rather simply by laying the necessary groundwork—and letting the body do the rest.

The ability for the human body to regenerate tissues lost to injury or disease may still be closer to science fiction than reality, but scientists at the Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, have gotten us one big step closer.

Reporting in the latest issue of the journal Acta Biomaterialia, Dr. Sang Jin Lee and his research team describe their ingenious new method for regrowing damaged muscle tissue in laboratory rodents—by supercharging the body’s own natural restorative abilities. As Lee explained in a news release:

“Working to leverage the body’s own regenerative properties, we designed a muscle-specific scaffolding system that can actively participate in functional tissue regeneration. This is a proof-of-concept study that we hope can one day be applied to human patients.”

Normally, the body’s muscles—as well as the majority of organs—sit atop a biological ‘scaffold’ created by a matrix of molecules secreted by surrounding cells. This scaffold gives the organs and muscle their three-dimensional structure.

Scientists have identified a protein that may help spur 'in body' muscle regeneration.

Scientists have identified a protein that may help spur ‘in body’ muscle regeneration.

As of right now, if doctors want to replace damaged muscle they have one of two options: either surgically transfer a muscle segment from one part of the body to the other, or engineer replacement muscle tissue in the lab from a biopsy. Both methods, while doable, are not ideal. In the first, you are reducing the strength of the donor muscle; in the second, you have the added challenge of standardizing the engineered cells so that they will graft successfully.

So, Lee and his team focused on a third way: coaxing the body’s own supply of adult stem cells—which are tissue specific and normally used for general small-scale maintenance—to rebuild the damaged muscle from within. Said Lee:

“Our aim was to bypass the challenges of both of these techniques and to demonstrate the mobilization of muscle cells to a target-specific site for muscle regeneration.”

In this study, the researchers developed a method to do just that in the laboratory animals. First, they implanted a new cellular scaffold into the rodents’ legs. After several weeks, they removed the scaffold to see whether any cells had latched on of their own accord.

Interestingly, the team found that without any additional manipulation, the scaffold had developed a network of blood vessels within just four weeks after implanting. They also observed the presence of some early-stage muscle cells. What the researchers wanted to do next was find a way to boost what they already observed naturally.

To do so, they tested whether proteins—previously known to be involved in muscle development—could boost the speed and amount of recruitment of muscle stem cells to the scaffold.

After a series of experiments, they found a leading candidate: a protein called insulin-like growth factor 1, or IGF-1. And when they injected IGF-1 into the newly-implanted scaffolds the difference was remarkable. These scaffolds had about four times as many cells when compared to the plain scaffolds. As Lee explained:

“The protein effectively promoted cell recruitment and accelerated muscle regeneration.”

The real work now begins, added Lee, whose team will now take their research to larger animal models, such as pigs, to see whether their technique can work on a far grander scale.

Stem Cell Stories that Caught our Eye: A Zebrafish’s Stripes, Stem Cell Sound Waves and the Dangers of Stem Cell Tourism

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.

The zebrafish (Danio rerio) owes its name to a repeating pattern of blue stripes alternating with golden stripes. [Credit: MPI f. Developmental Biology/ P. Malhawar]

The zebrafish (Danio rerio) owes its name to a repeating pattern of blue stripes alternating with golden stripes. [Credit: MPI f. Developmental Biology/ P. Malhawar]

How the Zebrafish Got its Stripes. Scientists in Germany have identified the different pigment cells that emerge during embryonic development and that determine the signature-striped pattern on the skins of zebrafish—one of science’s most commonly studied model organisms. These results, published this week in the journal Science, will help researchers understand how patterns, from stripes to spots to everything in between, develop.

In the study, scientists at the Max Planck Institute for Developmental Biology mapped how three distinct pigment cells, called black cells, reflective silvery cells, and yellow cells emerge during development and arrange themselves into the characteristic stripes. While researchers knew these three cell types were involved in stripe formation, what they discovered here was that these cells form when the zebrafish is a mere embryo.

“We were surprised to observe such cell behaviors, as these were totally unexpected from what we knew about color pattern formation”, says Prateek Mahalwar, first author of the study, in a news release.

What most surprised the research team, according to the news release, was that the three cell types each travel across the embryo to form the skin from a different direction. According to Dr. Christiane Nüsslein-Volhard, the study’s senior author:

“These findings inform our way of thinking about color pattern formation in other fish, but also in animals which are not accessible to direct observation during development such as peacocks, tigers and zebras.”

Sound Waves Dispense Individual Stem Cells. It happens all the time in the lab: scientists need to isolate and study a single stem cell. The trick is, how best to do it. Many methods have been developed to achieve this goal, but now scientists at the Regenerative Medicine Institute (REMEDI) at NUI Galway and Irish start-up Poly-Pico Technologies Ltd. have pioneered the idea of using sound waves to isolate living stem cells, in this case from bone marrow, with what they call the Poly-Pico micro-drop dispensing device.

Poly-Pico Technologies Ltd., a start-up that was spun out from the University of Limerick in Ireland, has developed a device that uses sound energy to accurately dispense protein, antibodies and DNA at very low volumes. In this study, REMEDI scientists harnessed this same technology to dispense stem cells.

These results, while preliminary, could help improve our understanding of stem cell biology, as well as a number of additional applications. As Poly-Pico CEO Alan Crean commented in a news release:

“We are delighted to see this new technology opportunity emerge at the interface between biology and engineering. There are other exciting applications of Poly-Pico’s unique technology in, for example, drug screening and DNA amplification. Our objective here is to make our technology available to companies, and researchers, and add value to what they are doing. This is one example of such a success.”

The Dangers of Stem Cell Toursim. Finally, a story from ABC News Australia, in which they recount a woman’s terrifying encounter with an unproven stem cell technique.

In this story, Annie Levington, who has suffered from multiple scleoris (MS) since 2007, tells of her journey from Melbourne to Germany. She describes a frightening experience in which she paid $15,000 to have a stem cell transplant. But when she returned home to Australia, she saw no improvement in her MS—a neuroinflammatory disease that causes nerve cells to whither.

“They said I would feel the effects within the next three weeks to a year. And nothing – I had noticed nothing whatsoever. [My neurologist] sent me to a hematologist who checked my bloods and concluded there was no evidence whatsoever that I received a stem cell transplant.”

Sadly, Levington’s story is not unusual, though it is not as dreadful as other instances, in which patients have traveled thousands of miles to have treatments that not only don’t cure they condition—they actually cause deadly harm.

The reason that these unproven techniques are even being administered is based on a medical loophole that allows doctors to treat patients, both in Australia and overseas, with their own stem cells—even if that treatment is unsafe or unproven.

And while there have been some extreme cases of death or severe injury because of these treatments, experts warn that the most likely outcome of these untested treatments is similar to Levington’s—your health won’t improve, but your bank account will have dwindled.

Want to learn more about the dangers of stem cell tourism? Check out our Stem Cell Tourism Fact Sheet.

A Tumor’s Trojan Horse: CIRM Researchers Build Nanoparticles to Infiltrate Hard-to-Reach Tumors

Some tumors are hard to find, while others are hard to destroy. Fortunately, a new research study from the University of California, Davis, has developed a new type of nanoparticle that could one day do both.

UC Davis scientists have developed a new type of nanoparticle to target tumor cells.

UC Davis scientists have developed a new type of nanoparticle to target tumor cells.

Reporting in the latest issue of Nature Communications, researchers in the laboratory of UC Davis’ Dr. Kit Lam describe a type of ‘dynamic nanoparticle’ that they created, which not only lights up tumors during an MRI or PET scan, but which may also serve as a microscopic transport vehicle, carrying chemotherapy drugs through the blood stream—and releasing them upon reaching the tumor.

This is not the first time scientists have attempted to develop nanoparticles for medicinal purposes, but is perhaps one of the more successful. As Yuanpei Li, one of the study’s co-first authors stated in a news release:

“These are amazingly useful particles. As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors.”

Nanoparticles can be constructed out of virtually any material—but the material used often determines for what purpose they can be used. Nanoparticles made of gold-based materials, for example, may be strong for diagnostic purposes, but have been shown to have issues with safety and toxicity. On the flip side, nanoparticles made from biological materials are safer, but inherently lack imaging ability. What would be great, the team reasoned, was a new type of nanoparticle that had the best qualities of both.

In this study, which was funded in part by CIRM, Lam and the UC Davis team devised a new type of nanoparticle that was ‘just right,’—simple to make, safe and able to perform the desired task, in this case: attack tumors.

Built of organic porphyrin and cholic acid polymers and coated with the amino acid cysteine, the 32 nanometer-wide particles developed in this study offer a number of advantages over other models. They are small enough to pass into tumors, can be filled with a chemo agent and with a specially designed cysteine coating, and don’t accidentally release their payload before reaching their destination.

And this is where the truly ingenious part kicks in. With a simple flash of light, the researchers could direct the particles to drop their payload—at just the right time, offering some intriguing possibilities for new ways to deliver chemotherapy drugs.

But wait, there’s more. The fact that these new particles, which the team are calling cysteine nanoparticles, or CNP’s, appear to congregate inside tumors means that they also end up being easy to spot on an MRI.

Continued Li in the same release:

“These particles can combine imaging and therapeutics. We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy. This is the fist nanoparticle to perform so many different jobs. From delivering chemo, photodynamic and photothermal therapies to enhancing diagnostic imaging. It’s the complete package.”

And while the team cautions that these results are preliminary, they open the door to an entirely new and far more exact method of drug delivery to tumors—no matter how well-hidden in the body they may be.

First of its kind stem cell production facility sets its sights on deadly childhood disease

We are used to hearing about immune suppression when transplanting organs or cells from one person to another. It’s a necessary step in preventing the body from attacking the transplanted material. Now Children’s Hospital of Orange County (CHOC) has just unveiled its newest tool to treat rare childhood diseases. Instead of focusing on immune suppression this focuses on immune-matching.

CHOC's new stem cell production facility

CHOC’s new stem cell production facility

CHOC has opened up a new stem cell production facility. It’s funded by CIRM and it’s a state-of-the-art mini clean room/manufacturing facility that will allow researchers to produce patient-specific cells for future immune-matching therapies.

“We are excited. We’ve been planning this for at least five years,” says Philip Schwartz, Ph.D., senior scientist at the CHOC Children’s Research Institute and managing director of the National Human Neural Stem Cell Resource.

“The major thing is that the footprint is much smaller than a traditional stem cell manufacturing facility, it’s all housed in one room so that keeps the cost down. The device we use to reproduce the cells is also much smaller so this set up doesn’t require multiple rooms and complex pass-throughs as you move from one room to another. All that meant the cost was only around $500,000 which is many times smaller than the more conventional facility.”

Dr. Schwartz is wasting little time putting the new facility to work. It’s already up and running and culturing cells for his work in developing a treatment for mucopolysaccharidosis (MPS-1), a rare neurodegenerative disease that usually kills children before the age of 10.

He is working on a kind of 1-2 punch approach to the disease. Using donated umbilical cord blood to help replace the child’s damaged immune system and then turning some of those blood stem cells into neural cells, the kind damaged by MPS-1, and transplanting those into the brain to repair and prevent further damage.

“This is a really interesting approach. Bone marrow transplants treat a neck down disease. Brain transplants treat a neck up disease. But conditions like MPS-1 are system wide and need both a neck down and neck up approach. Our approach could help combine those and because the cells are carefully matched also mean they won’t need to be on immune-suppressant therapy for life.”

Dr. Schwartz says animal studies using this two pronged approach have been very encouraging but he cautions there is still a lot of work to do before it would be ready for a clinical trial in people. However, if this approach is effective then it could be useful for more than just MPS-1:

“I have a high level of confidence that this will work and if it does work then we can use it in other conditions as well, such as Multiple Sclerosis. Some clinical studies show that MS patients with leukemia who got a bone marrow transplant also saw a decrease in their MS symptoms.”

Kevin McCormack

Mapping Metastasis: Scientists Discover how Cancer Cells Colonize Distant Organs

How does cancer spread? How does it traverse from one organ to the next—often undetected—until it has colonized the far reaches of the human body? And more importantly, how can researchers stop this from happening?

These questions plague even the most renowned experts, but new research from scientists at Brown University has uncovered clues to cancers’ unique ability to invade our bodies—offering important insight into how we might develop tools to stop this disease’s most dangerous ability.

Cancer cells advance across a microchip designed to be an obstacle course for cells. The device sheds new light on how cancer cells invade and could be used to test drugs aimed at preventing cancer spread. [Credit: Ian Y. Wong / Brown University]

Cancer cells advance across a microchip designed to be an obstacle course for cells. The device sheds new light on how cancer cells invade and could be used to test drugs aimed at preventing cancer spread. [Credit: Ian Y. Wong / Brown University]

Reporting in this week’s issue of Nature Materials, biomedical engineer Dr. Ian Wong and his team devised a special microchip technology that tracks individual cancer cells as they navigate from one end of the chip to the other. Importantly, this tool uncovered how cancer cells hijack an otherwise normal cellular process to infect the body.

This process, called the epithelial-mesenchymal transition (or ‘EMT’) normally occurs in the developing embryo, when one type of cells, called epithelial cells, transforms into mesenchymal cells. Epithelial cells tend to clump together into larger groups, whereas mesenchymal cells can more easily and more quickly break away from the pack and travel individually. This transition is crucial to embryonic development, as it allows for cells to get to where they need to be at the appropriate time.

However, scientists have recently begun to hypothesize that cancer uses EMT as a tool to help it metastasize—traversing throughout the body and setting up shop in various tissues and organs. Metastasis is one of the biggest hurdles to eradicating cancer, and is responsible for 90% of all cancer-related deaths.

As Wong explained in yesterday’s news release:

“People are really interested in how EMT works and how it might be associated with tumor spread, but nobody has been able to see how it happens. We’ve been able to image these cells in a biomimetic system and carefully measure how they move.”

The research team used microchip technology to essentially build a microscopic ‘obstacle course,’ which cancer cells had to navigate. Made from a silicon wafer and tiny pillars just 10 micrometers in diameter and spaced so close together with just enough space for the cells to squeeze in between. Then, using fluorescent dye and time-lapse photography, they watched as the cells moved from one end of the chip to the other. According to Wong:

“We can track individual cells, and because the size and spacing of these pillars is highly controlled, we can start to do statistical analysis and categorize these cells as they move.”

This amazing video revealed that cells moved across the plate at two different speeds.

Most moved slowly, often clumping together, exhibiting classic epithelial cell behavior. But a minority of cells sped through the obstacle course individually—breaking away from the pack. These cells, Wong argues, have switched to mesenchymal cells after experiencing EMT.

“In the context of cell migration, EMT upgrades cancer cells from an economy model to a fast sports car. Our technology enabled us to track the motion of thousands of ‘cars’ simultaneously, revealing that…some sports cars break out of traffic and make their way aggressively to distant locations.”

These ‘breakaway’ cells are how cancer can reach, invade and, ultimately destroy, distant organs.

But this newfound knowledge also hints at a possible therapeutic strategy: developing a drug that reverses EMT in cancer cells, keeping them in clumps and slowing their progress.

“An interesting therapeutic strategy might be to develop drugs that downgrade mesenchymal ‘sports cars’ back to epithelial ‘economy models’ in order to keep them stuck in traffic, rather than aggressively invading surrounding tissues.’

Want to learn more about how cancer spreads? Check out our Solid Tumor Fact Sheet.

Revealing the Invisible: Scientists Uncover the Secret Ingredient to Making Blood-Forming Stem Cells

They are among the most versatile types of stem cell types in the body. They live inside bone marrow and in the blood of the umbilical cord. They can be used to treat deadly cancers such as leukemia (Leukemia Fact Sheet) as well as many blood disorders. But no one really understood the details of how they were made.

How are blood stem cells made? Australian scientists have uncovered a missing ingredient.

How are blood stem cells made? Australian scientists have uncovered a missing ingredient.

That is, until scientists at the Australian Regenerative Medicine Institute devised an ingenious way to view the formation of these hematopoetic stem cells (HSC’s) in unprecedented detail. And in so doing, found the missing ingredient that may make it possible to grow fully functioning versions of these cells in the lab—opening the door to treating a wide range of blood and immune disorders. Attempts to grow these in the past have resulted in immature versions more like those found in a fetus than those in an adult.

One of the study’s senior authors, Dr. Peter Currie, even goes so far as to say this discovery represents a ‘Holy Grail’ for the field. As he explained in today’s news release:

“HSCs are one of the best therapeutic tools at our disposal because they can make any blood cell in the body. Potentially we could use these cells in may more ways than current transplantation strategies to treat serious blood disorders and diseases, but only if we can figure out how they are generated in the first place.”

Fortunately, this new study—published today in the journal Nature—brings researchers closer to that goal.

Using high-resolution microscopic imaging techniques, Currie and his team filmed the development of a zebra fish embryo—with a particular focus on HSCs. When they played back the video, the team saw something that no one had noticed before. In order for HSCs to develop properly, they needed a little support from another cell type known as endotomes. As Currie explained:

“Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged [HSCs]. Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.”

It appears that this unique relationship between endotomes and HSCs is key to HSC formation, a process that had for so long evaded researchers. But armed with this newfound knowledge, the team could one day produce different types of blood cells ‘on demand’—and potentially treat many types of blood disorders. This has been such a tough nut to crack with such great potential CIRM convened an international panel of experts to produce a whitepaper on the issue.

The team’s immediate next steps, according to Currie, are to pinpoint the molecular switches themselves (within endotomes and HSCs) that trigger the production of these stem cells. And while these results are preliminary, he is cautiously optimistic about the potential power to treat a variety of illnesses:

“Potentially, it’s imaginable that you could even correct genetic defects in cells and then transplant them back into the body.”