Stem Cell Stories that Caught our Eye: Skin Cells to Brain Cells in One Fell Swoop, #WeAreResearch Goes Viral, and Genes Helps Stem Cells Fight Disease

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.

Building a Better Brain Cell. Thanks to advances in stem cell biology, scientists have found ways to turn adult cells, such as skin cells, back into cells that closely resemble embryonic stem cells. They can then coax them into becoming virtually any cell in the body.

But scientists have more recently begun to devise ways to change cells from one type into another without first having to go back to a stem cell-like state. And now, a team from Washington University in St. Louis has done exactly that.

As reported this week in New Scientist, researcher Andrew Yoo and his team used microRNAs—a type of ‘signaling molecule’—to reprogram adult human skin cells into medium spiny neurons(MSNs), the type of brain cell involved in the deadly neurodegenerative condition, Huntington’s disease.

“Within four weeks the skin cells had changed into MSNs. When put into the brains of mice, the cells survived for at least six months and made connections with the native tissue,” explained New Scientist’s Clare Wilson.

This process, called ‘transdifferentiation,’ has the potential to serve as a faster, potentially safer alternative to creating stem cells.

#WeAreResearch Puts a Face on Science. The latest research breakthroughs often focus on the science itself, and deservedly so. But exactly who performed that research, the close-knit team who spent many hours at the lab bench and together worked to solve a key scientific problem, can sometimes get lost in the shuffle.

#WeAreResearch submission from The Thomson Lab at the University of California, San Francisco. This lab uses optogenetics, and RNAseq to probe cell fate decisions.

#WeAreResearch submission from The Thomson Lab at the University of California, San Francisco. This lab uses optogenetics, and RNAseq to probe cell fate decisions.

Enter #WeAreResearch, a new campaign led by the American Society for Cell Biology (ASCB) that seeks to show off science’s more ‘human side.’

Many California-based stem cell teams have participated—including CIRM grantee Larry Goldstein and his lab!

Check out the entire collection of submissions and, if you’re a member of a lab, submit your own. Prizes await the best submissions—so now’s your chance to get creative.

New Genes Help Stem Cells Fight Infection. Finally, UCLA scientists have discovered how stem cells ‘team up’ with a newly discovered set of genes in order to stave off infection.

Reporting in the latest issue of the journal Current Biology, and summarized in a UCLA news release, Julian Martinez-Agosto and his team describe how two genes—adorably named Yorkie and Scalloped—set in motion a series of events, a molecular Rube Goldberg device, that transforms stem cells into a type of immune system cell.

Importantly, the team found that without these genes, the wrong kind of cell gets made—meaning that these genes play a central role in the body’s healthy immune response.

Mapping out the complex signaling patterns that exist between genes and cells is crucial as researchers try and find ways to, in this case, improve the body’s immune response by manipulating them.

Stem Cell Stories that Caught our Eye: Perspective on “Walking” Patient, Blood Stem Cells have a Helper and Three Clinical Trials at One Campus

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.

Some perspective on nasal stem cells and ”walking” patient. PZ Meyers writing on ScienceBlogs did a good job of putting some perspective into the hype in many news outlets about the spinal cord injury patient who was treated with nasal stem cells. He starts out admitting he was “incredulous” that there was anything to the study, but after a thorough reading of the actual journal article he was convinced that there was some real, though modest gain in function for the patient. His conclusion:

“Sad to say, the improvements in the man’s motor and sensory ability are more limited and more realistic than most of the accounts would have you think.”

The research team actually reported on three patients. One got barely noticeable improvement; the patient in the news reports regained about 25 percent of function—which is indisputably a major gain in this population—and the third was somewhere in between.

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Meyer speculated about a reason for the improvements that was left out of most press reports. In addition to the stem cell harvested from the patients’ own nasal passages injected on either side of the injury the team also harvested nerve fibers from the patients legs and transplanted them across the site of the injury. They hoped the nerve strands would act as a bridge for the stem cells to grow and close the gap. It is also possible that being nerve cells they could provide the right cell-to-cell signals directing the nasal stem cells to become nerves. Meyers closed with an appropriate summary:

“I think there’s good reason to be optimistic and see some hope for an effective treatment for serious spinal cord injuries, but right now it has to be a realistic hope — progress has been made. A cure does not exist.”

Body’s own helper for blood stem cells found. In a case of the children ordering around the parents, a team at the Stowers Institute in Kansas City found that one of the progeny of blood-forming stem cells in the bone marrow can control the activity of the stem cells. In particular, they were looking at megacarocytes, the relatively rare bone marrow cells that normally produce the blood platelets you need for clotting a wound.

Blood stem cells are the most common stem cell therapy today, but one plagued by our limited ability to control their growth. Knowing this involvement of their offspring gives researcher a new avenue to search for ways to grow the much needed parent stem cells. Genetic Engineering & Biotechnology News wrote up the findings.

(Yes, I may be the only person in World Series-obsessed San Francisco writing something positive about Kansas City this week.)

Three clinical trails launched at just one campus. We have written individually about three clinical trials that began in the last month at the University of California, San Diego. Now, the university has written a good wrap up of the three trials that got posted to ScienceDaily.

Collectively, the three trials show the breadth of stem cell research starting to reach patients. One trial, for diabetes, uses cells derived from embryonic stem cells encased in a pouch to protect them from immune rejection. Another uses cells derived from fetal nerve stem cells to treat spinal cord injury. And the third involves a drug that targets the cancer stem cells that are believed to cause much of the spread of the disease and resistance to chemotherapy in cancer patients.

CIRM is funding two of the three trials and supported much of the basic science that led to the third. We expect to be funding 10 projects with approved clinical trials by the end of the year. The field is moving.

Don Gibbons

These Are the Cells You’re Looking for: Scientists Devise New Way to Extract Bone-Making Stem Cells from Fat

Buried within our fat tissue are stashes of stem cells—a hidden reservoir of cells that, if given the right cues, can transform into cells that make up bone, cartilage or fat. These cells therefore represent a much-needed store for regenerative therapies that rebuild bone or cartilage lost to disease or injury.

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). [Credit: Darling lab/Brown University]

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). The center image shows both types of cells prior to sorting [Credit: Darling lab/Brown University]

The only problem with these tucked-away cellular reservoirs, however, is identifying them and getting them out.

But now, researchers at Brown University have devised a unique method of identifying, extracting and then cultivating these bone-producing stem cells. Their results, published today in the journal Stem Cell Research & Therapy, seem to offer a much-needed alternative resource for growing bone.

Traditional methods attempting to locate and extract these stem cells focused on proteins that reside on the surface of the cells. Find the proteins, scientists reasoned, and you’ve found the cell.

Unfortunately, that method was not fool proof, and many argued that it wasn’t finding all the cells that reside in the fat tissue. So Brown scientists, led by Dr. Eric Darling found an alternative.

They knew that a gene called ALPL is an indicator of bone-making cells. If the gene is switched on, the cell has the potential to make bone. If it’s switched off, it does not. So Darling and his team devised a fluorescent marker, or tag, that stuck to the cells with activated ALPL. They then used a special machine to sort the cells: those that glowed went into one bucket, those that did not went into the other.

To prove that these ALPL-activated cells were indeed capable of becoming bone and cartilage, they then cultivated them for several weeks in a petri dish. Not only did they transform into the right cell types—they did so in greater numbers than cells extracted using traditional methods.

Hetal Marble, a graduate student in Darling’s lab and the paper’s first author, argues that tagging genes—rather than surface proteins—in order to distinguish and weed out cell types represents an important paradigm shift in the field. As he stated in a press release:

“Approaches like this allow us to isolate all the cells that are capable of doing what we want, whether they fit the archetype of what a stem cell is or is not. The paradigm shift is thinking about isolating populations that are able to achieve an end point rather than isolating populations that fit a strictly defined archetype.”

While their method is both precise and accurate, there is one drawback: it is slow.

Currently, it takes four days to tag, extract and cultivate the bone-making cells. In the future, the team hopes they can shorten this time frame so that they could perform the required steps within a single surgical session. As Darling stated:

“If you can take a patient into the OR, isolate a bunch of their cells, sort them and put them back in—that’s ideally where we’d like to go with this.”

Cells’ Knack for Hoarding Proteins Inadvertently Kickstarts the Aging Process

Even cells need to take out the trash—mostly damaged or abnormal proteins—in order to maintain a healthy clean environment. And scientists are now uncovering the harmful effects when cells instead begin to hoard their garbage.

Cells' penchant for hoarding proteins may spur the cellular aging process, according to new research.

Cells’ penchant for hoarding proteins may spur the cellular aging process, according to new research. [Labyrinth (1986)]

Aging, on the cellular level is—at its core—the increasing inability for cells to repair themselves over time. As cells begin to break down faster than they can be repaired, the risk of age-related diseases escalates. Cancer, heart disease and neurological conditions such as Alzheimer’s disease are some of aging’s most deadly effects.

As a result, scientists have long searched for ways to give our cells a little help and improve our quality of life as we age. For example, recent research has pointed to a connection between fasting (restricting calories) and a longer lifespan, though the molecular mechanisms behind this connection remain somewhat cryptic.

But now Dr. Daniel Gottschling, a scientist at the Fred Hutchinson Cancer Research Center and an aging expert, has made extraordinary progress toward solving some of the mysteries of aging.

In two studies published this month in the Proceedings of the National Academy of Sciences and eLife, Gottschling and colleagues discover that a particular long-lasting protein builds up over time in certain cell types, causing the buildup of a protein hoard that damages the cell beyond repair.

Clearing out the Cobwebs

Some cells, such as those that make up the skin or that reside in the gut, are continually replenished by a stockpile of adult stem cells. But other cells, such as those found in the eye and brain, last for years, decades and—in some cases—our entire lifetimes.

Within and surrounding these long-lived cells are similarly long-lived proteins which help the cell perform essential functions. For example, the lens of the human eye, which helps focus light, is made up of these proteins that arise during embryonic development and last for a lifetime.

Dr. Daniel Gottschling is looking to unlock the mysteries behind cellular aging.

Dr. Daniel Gottschling is looking to unlock the mysteries behind cellular aging. [Image courtesy of the Fred Hutchinson Cancer Research Center]

“Shortly after you’re born, that’s it, you get no more of that protein and it lives with you the rest of your life,” explained Gottschling.

As a result, if those proteins degrade and die, new ones don’t replace them—the result is the age-related disease called cataracts.

But scientists weren’t exactly sure of the relationship between these dying proteins and the onset of conditions such as cataracts, and other disease related to aging. Did these conditions occur because the proteins were dying? Or rather because the proteins were building up to toxic levels?

So Gottschling and his team set up a series of experiments to find out.

Stashing Trash

They developed a laboratory model by using yeast cells. Interestingly, yeast cells share several key properties with human stem cells, and are often the focus of early-stage research into basic, fundamental concepts of biology.

Like stem cells, yeast cells grow and divide asymmetrically. In other words, a ‘mother’ cell will produce many ‘daughter’ cells, but will itself remain intact. In general, yeast mother cells produce up to 35 daughter cells before dying—which usually takes just a few days.

 Yeast “mother” cells budding and giving birth to newborn “daughter” cells.  [Image courtesy of Dr. Kiersten Henderson / Gottschling Lab]

Yeast “mother” cells budding and giving birth to newborn “daughter” cells.
[Image courtesy of Dr. Kiersten Henderson / Gottschling Lab]

Here, the research team used a special labeling technique that marked individual proteins that exist within and surrounding these mother cells. These microscopic tracking devices then told researchers how these proteins behaved over the entire lifespan of the mother cell as it aged.

The team found a total of 135 long-lived proteins within the mother cell. But what really surprised them was what they found upon closer examination: all but 21 of these 135 proteins appeared to have no function. They appeared to be trash.

“No one’s ever seen proteins like this before [in aging],” said Nathanial Thayer, a graduate student in the Gottschling Lab and lead author of one of the studies.

Added Gottschling, “With the number of different fragments [in the mother cell], we think they’re going to cause trouble. As the daughter yeast cells grow and split off, somehow mom retains all these protein bits.”

This startling discovery opened up an entirely new set of questions, explained Gottschling.

“It’s not clear whether the mother’s trash keeper function is a selfless act designed to give her daughters the best start possible, or if she’s hanging on to them for another reason.”

Hungry, Hoarding Mother Cells

So Gottschling and his team took a closer look at one of these proteins, known as Pma1.

Recent work by the Gottschling Lab found that cells lose their acidity over time, which itself leads to the deterioration of the cells’ primary energy source. The team hypothesized that Pma1 was somehow intricately tied to corresponding levels of pH (high pH levels indicate an acidic environment, while lower pH levels signify a more basic environment).

In the second study published in eLife, led by Postdoctoral Fellow Dr. Kiersten Henderson, the team made several intriguing discoveries about the role of Pma1.

First, they uncovered a key difference between mother and daughter cells: daughter cells are born with no Pma1. As a result, they are far more acidic than their mothers. But when they ramped up Pma1 in the mother cells, the acidity levels in subsequent generations of daughter cells changed accordingly.

“When we boosted levels of the protein, daughter cells were born with Pma1 and became more basic (they had a lower pH), just like their mothers.”

Further examination uncovered the true relationship between Pma1 and these cells. At its most fundamental, Pma1 helps the mother cells eat.

“Pma1 plays a key role in cellular feeding,” said Gottschling. “The protein sits on the surface of cells and helps them take in nutrients from their environment.”

Pma1 gives the mother cell the ability to gorge herself. The more access to food she has, the easier it is for her to produce more daughter cells. By hoarding Pma1, the mother cell can churn out more offspring. Unfortunately, she is also signing her own death certificate—she’s creating a more basic environment that, in the end, proves toxic and contributes to her death.

The hoarding, it turns out, may not all be due to the mother cells’ failure to ‘take out the trash.’ Instead, she wants to keep eating and producing daughters—and hoarding Pma1 allows her to do just that.

“There’s this whole trade off of being able to divide quickly and the negative side is that the individual, the mother, does not get to live as long.”

Together, the results from these two studies provide a huge boost for researchers like Gottschling who are trying to unravel the molecular mysteries of aging. But the process is incredibly intricate, and there will likely be no one simple solution to improving quality of life as we get older.

“The whole issue of aging is so complex that we’re still laying the groundwork of possibilities of how things can go awry,” said Gottschling. “And so we’re still learning what is going on. We’re defining the aging process.”

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.”

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.

Disease in a Dish – That’s a Mouthful: Using Human Stem Cells to Find ALS Treatments

Saying “let’s put some shrimp on the barbie” will whet an Australian’s appetite for barbequed prawns but for an American it conjures up an odd image of placing shrimp on a Barbie doll. This sort of word play confusion doesn’t just happen across continents but also between scientists and the public.

Take “disease in a dish” for example. To a stem cell scientist, this phrase right away describes a powerful way to study human disease in the lab using a Nobel Prize winning technique called induced pluripotent stem cells (iPSC). But to a non-scientist it sounds like a scene from some disgusting sci-fi horror cooking show.

Our latest video Disease in a Dish: That’s a Mouthful takes a lighthearted approach to help clear up any head scratching over this phrase. Although it’s injected with humor, the video focuses on a dreadful disease: amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig’s disease, it’s a disorder in which nerve cells that control muscle movement die. There are no effective treatments and it’s always fatal, usually within 3 to 5 years after diagnosis.

To explain disease in a dish, the video summarizes a Science Translation Medicine publication of CIRM-funded research reported by the laboratory of Robert Baloh, M.D., Ph.D., director of Cedars-Sinai’s multidisciplinary ALS Program. In the study, skin cells from patients with an inherited form of ALS were used to create nerve cells in a petri dish that exhibit the same genetic defects found in the neurons of ALS patients. With this disease in a dish, the team identified a possible cause of the disease: the cells overproduce molecules causing a toxic buildup that affects neuron function. The researchers devised a way to block the toxic buildup, which may point to a new therapeutic strategy.

In a press release, Clive Svendsen, Ph.D., a co-author on the publication and director of the Cedars-Sinai Regenerative Medicine Institute had this perspective on the results:

“ALS may be the cruelest, most severe neurological disease, but I believe the stem cell approach used in this collaborative effort holds the key to unlocking the mysteries of this and other devastating disorders.”

The video is the pilot episode of Stem Cells in Your Face, which we hope will be an ongoing informational series that helps explain the latest advances toward stem cell-based therapies.

For more information about CIRM-funded ALS research, visit our ALS 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.”

Breast Cancer Commandeers Mammary Stem Cells for Own, Nefarious Purposes

Most instances of breast cancer happen later in life—often after menopause. In many cases, the cancer progresses slowly, over a period of months or even years, often giving physicians precious time to implement a treatment plan, successfully battling that cancer into remission.

A section from a mammary 'outgrowth' harvested at lactation. [Credit: UC San Diego School of Medicine]

A section from a mammary ‘outgrowth’ harvested at lactation. [Credit: UC San Diego School of Medicine]

But there is another far more aggressive form of breast cancer that tends to develop earlier, often immediately following pregnancy. And now, researchers at the University of California, San Diego (UCSD) have discovered how this form of cancer hijacks a woman’s own stem cells to grow quickly and spread throughout the body.

Reporting in the latest issue of the journal Developmental Cell, UCSD stem cell researchers Drs. David Cheresh and Jay Desgrosellier and their teams have found a link between the molecular signaling switches that spur this aggressive, post-pregnancy breast cancer—and mammary stem cells that are normally activated during pregnancy.

These findings, say Cheresh, offer key insight into how scientists may develop better treatments for this form of breast cancer. As he stated in a news release:

“By understanding a fundamental mechanism of mammary gland development during pregnancy, we have gained a rare insight into how aggressive breast cancer might be treated.”

Normally, pregnancy activates a special group of stem cells in the mammary gland. Their job is to ready the expectant mother for feeding the newborn baby. By the time the baby is born, however, these stem cells go back into hibernation.

However, in some women, these mammary stem cells get hijacked by cancer cells. Rather than the mammary stem cells shutting down by the time milk production begins, cancer cells keep them switched on—which then contributes to the progression of cancer.

These findings shed much-needed light on the complex relationship between breast cancer and pregnancy. However, the authors caution that these findings don’t imply that becoming pregnant causes breast cancer. Rather, as Cheresh explained:

“Our work doesn’t speak to the actual cause of cancer. Rather, it explains what can happen once cancer has been initiated.”

Cheresh, who has received CIRM support for related work, has pinpointed a protein called CD61 that may promote the progression of breast cancer. CD61 has already been implicated in cancer metastasis and resistance to cancer drugs, so it makes sense that it would play a role in breast cancer as well.

Importantly, the discovery of a potential connection between CD61 and this form of breast cancer may ultimately open up new avenues for treating this type of cancer more successfully.

“Detecting CD61 might help doctors determine what kind of therapeutic approach to use, knowing that they might be dealing with a more aggressive yet treatable form of breast cancer. For example, there are existing drugs that block CD61 signaling, which might be another potential aspect of treatment.”

Want to learn more about breast cancer and stem cells? Check out our Solid Tumor Fact Sheet.