CIRM Supported Scientist Makes Surprising Discovery with Parasitic Gut Worms

 

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Image of gut lining and parasites.  Photo courtesy of UCSF/ Michael Fortes

 

It’s no secret that researchers have long believed adult stem cells could contribute to wound healing in the gut and skin, but in a new paper in Nature — a group of scientists at UC San Francisco made a surprising discovery.

Through several experiments using parasitic worms in the mouse gut, they found that as parasites dug into the intestinal walls of mice, the gut responded in an unexpected way – by reactivating a type of cell growth previously seen in fetal tissues.

So why is this important?

Simply put, it gives scientists new targets to go after. According to UCSF CIRM supported scientist Ophir Klein, MD, Ph.D., this discovery could be paradigm-shifting in terms of our understanding of how the mammalian body can repair damage and could help scientists develop more ways to enhance the body’s natural healing abilities.

Adult stem cells in the intestines are vital for maintaining the digestive status quo. The gut lining is made up of epithelial cells which absorb nutrients and produce protective mucus. These cells are replaced every few days by the stem cells at the base of crypts — indentations in the gut lining. Researchers expected that the same stem cells could also help repair tears in the gut.

How did they do it?

Larvae from parasites like H. polygyrus invade the gut lining in a mouse’s intestine, burying themselves to develop in the tissue. Based on prevailing ideas in the field, the scientists predicted that, in response, nearby stem cells would increase their productivity and patch up the worm-created wounds, but that is not what happened.

Instead, signs of the stem cells in worm-infected areas disappeared entirely; fluorescent markers that should have been expressed by one of the genes in the regular stem cell program completely vanished. And yet, even with no identifiable stem cells in the area, the wounded tissue regenerated more quickly than ever.

Researchers spent years trying to resolve this mystery and after a number of false starts and dead ends, the team eventually noticed the recurrence of a different gene, known as Sca-1.

Using antibody staining for the Sca-1 protein, the researchers realized that where the stem cell genes had disappeared, a different gene program was expressed instead: one that resembled the way that mouse guts develop in utero.

Upon their discovery, the researchers wondered whether the reactivation of this fetal program was a specific response to parasite infections, or if it could be a general strategy for many kinds of gut injury. Additional experiments showed that shutting down gut stem cells with irradiation or genetically targeting them for destruction triggered aspects of the same response: despite an absence of detectable stem cell activity, undifferentiated tissue grew rapidly nonetheless.

Later, once the acute injury is repaired, the gut may return to the normal stem cell program of producing differentiated cells that perform specific functions.

Many other injured tissues could benefit from the ability to quickly and efficiently make generalized repairs before returning to specialized adult cell production, opening up therapeutic opportunities. For example, developing treatments that bestow an ability to control the change between adult and fetal genetic programs might offer new strategies to manage conditions such as inflammatory bowel disease (IBD).

Fish umbrellas and human bone: protecting blood stem cells from the sun’s UV rays

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Most people probably do not question the fact that human blood stem cells – those that give rise to all the cells in our blood – live inside the marrow of our bones, called a stem cell “niche”. But it is pretty odd when you stop to think about it. I mean, it makes sense that the hard, calcium-rich structure of bones provide our bodies with a skeleton but why is it also responsible for making our blood?

This week, researchers at Harvard report in Nature that the answer may come down to protecting these precious cells from the DNA-damaging effects of UV radiation from the sun. They arrived at those insights by examining zebrafish which harbor blood stem cells, not in their bones, but in their kidneys. Fredrich Kapp, MD, the first author of the report, was trying to analyze blood stem cells in zebrafish under the microscope but noticed a layer of other cells on top of the kidney was obscuring his view.

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In a zebrafish larva (illustration above), a dark umbrella formed by pigmented cells (white arrows point to these black spots in box, left) in the kidney protects vulnerable stem cells from damaging UV light. Right image is a closeup of the box. Scale bars equal 100 micrometers (left) and 50 micrometers (right). Credit: F. Kapp et al./Nature 2018
Read more at: https://phys.org/news/2018-06-blood-cells-bones.html#jCp

That layer of cells turned out to be melanocytes which produce melanin a pigment that gives our skin color. Melanin also protects our skin cells from the sun’s UV radiation which damages our DNA and can cause genetic mutations. In a press release, Kapp recalled his moment of insight:

“The shape of the melanocytes above the kidney reminded me of a parasol, so I thought, do they provide UV protection to blood stem cells?”

To answer his question, he and his colleagues compared the effects of UV radiation on normal zebrafish versus mutant zebrafish lacking the layer of melanocytes. Confirming Kapp’s hypothesis, the fish missing the melanocyte layer had fewer blood stem cells. Simply turning the normal fish upside down and exposing them to the UV rays also depleted the blood stem cells.

And here’s where the story gets really cool. In studying frogs – animals closer to us on the evolutionary tree – they found that as the tadpole begins to grow legs, their blood stem cells migrate from the melanocyte-covered kidney cells to inside the bone marrow, an even better form of UV protection. Senior author Leonard Zon explained the importance of this finding:

“We now have evidence that sunlight is an evolutionary driver of the blood stem cell niche. As a hematologist and oncologist, I treat patients with blood diseases and cancers. Once we understand the niche better, we can make blood stem cell transplants much safer.”

 

 

Using biological “codes” to generate neurons in a dish

BrainWavesInvestigators at the Scripps Research Institute are making brain waves in the field of neuroscience. Until now, neuroscience research has largely relied on a variety of animal models to understand the complexities of various brain or neuronal diseases. While beneficial for many reasons, animal models do not always allow scientists to understand the precise mechanism of neuronal dysfunction, and studies done in animals can often be difficult to translate to humans. The work done by Kristin Baldwin’s group, however, is revolutionizing this field by trying to re-create this complexity in a dish.

One of the primary hurdles that scientists have had to overcome in studying neuronal diseases, is the impressive diversity of neuronal cell types that exist. The exact number of neuronal subtypes is unknown, but scientists estimate the number to be in the hundreds.

While neurons have many similarities, such as the ability to receive and send information via chemical cues, they are also distinctly specialized. For example, some neurons are involved in sensing the external environment, whereas others may be involved in helping our muscles move. Effective medical treatment for neuronal diseases is contingent on scientists being able to understand how and why specific neuronal subtypes do not function properly.

In a study in the journal Nature, partially funded by CIRM, the scientists used pairs of transcription factors (proteins that affect gene expression and cell identity), to turn skin stem cells into neurons. These cells both physically looked like neurons and exhibited characteristic neuronal properties, such as action potential generation (the ability to conduct electrical impulses). Surprisingly, the team also found that they were able to generate neurons that had unique and specialized features based on the transcription factors pairs used.

The ability to create neuronal diversity using this method indicates that this protocol could be used to recapitulate neuronal diversity outside of the body. In a press release, Dr. Baldwin states:

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Kristin Baldwin, PhD

“Now we can be better genome detectives. Building up a database of these codes [transcription factors] and the types of neurons they produce can help us directly link genomic studies of human brain disease to a molecular understanding of what goes wrong with neurons, which is the key to finding and targeting treatments.”

These findings provide an exciting and promising tool to more effectively study the complexities of neuronal disease. The investigators of this study have made their results available on a free platform called BioGPS in the hopes that multiple labs will delve into the wealth of information they have opened up. Hopefully, this system will lead to more rapid drug discovery for disease like autism and Alzheimer’s

Stem Cell Roundup: Backup cells to repair damaged lungs; your unique bowels; and California Cures, 71 ways CIRM is changing the face of medicine

It’s good to have a backup plan

3D illustration of Lungs, medical concept.

Our lungs are amazing things. They take in the air we breathe and move it into our blood so that oxygen can be carried to every part of our body. They’re also surprisingly large. If you were to spread out a lung – and I have no idea why you would want to do that – it would be almost as large as a tennis court.

But lungs are also quite vulnerable organs, relying on a thin layer of epithelial cells to protect them from harmful materials in the air. If those materials damage the lungs our body calls in local stem cells to repair the injury.

Now researchers at the University of Iowa have identified a new group of stem cells, called glandular myoepithelial cells (MECs), that also appear to play an important role in repairing injuries in the lungs.

These MECs seem to be a kind of “reserve” stem cell, waiting around until they are needed and then able to spring into action and develop into new replacement cells in the lungs.

In a news release study author Preston Anderson, said these cells could help develop new approaches to lung regeneration:

“We demonstrated that MECs can self-renew and differentiate into seven distinct cell types in the airway. No other cell type in the lung has been identified with this much stem cell plasticity.”

The study is published in Cell Stem Cell.

Your bowels are unique

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Not to worry, that’s a plastic model of  a bowel

If you are eating as you read this, you should either put your food down or skip this item for now. A new study on bowel cancer says that every tumor is unique and every cell within that tumor is also genetically unique.

Researchers in the UK and Netherlands took samples of normal bowel tissue and cancerous bowel tissue from three people with colorectal cancer. They then grew these in the labs and turned them into mini 3D organoids, so they could study them in greater detail.

In the study, published in the journal Nature, the researchers say they found that tumor cells, not surprisingly, had many more mutations than normal cells, and that not only was each bowel cancer genetically different from each other, but that each cell they studied within that cancer was also different.

In a news release, Prof Sir Mike Stratton, joint corresponding author on the paper from the Wellcome Sanger Institute, said:

“This study gives us fundamental knowledge on the way cancers arise. By studying the patterns of mutations from individual healthy and tumour cells, we can learn what mutational processes have occurred, and then look to see what has caused them. Extending our knowledge on the origin of these processes could help us discover new risk factors to reduce the incidence of cancer and could also put us in a better position to create drugs to target cancer-specific mutational processes directly.”

California Cures: a great title for a great book about CIRM

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CIRM Board Chair Jonathan Thomas (L) and Don Reed

One of the first people I met when I started working at CIRM was Don Reed. He impressed me then with his indefatigable enthusiasm, energy and positive outlook on life. Six years later he is still impressing me.

Don has just completed his second book on stem cell research charting the work of CIRM. It’s called “California Cures: How the California Stem Cell Research Program is Fighting Your Incurable Disease”. It’s a terrific read combining stories about stem cell research with true tales about Al Jolson, Enrico Caruso and how a dolphin named Ernestine burst Don’s ear drum.

On his website, Stem Cell Battles, Don describes CIRM as a “scrappy little stage agency” – I love that – and says:

“No one can predict the pace of science, nor say when cures will come; but California is bringing the fight. Above all, “California Cures” is a call for action. Washington may argue about the expense of health care (and who will get it), but California works to bring down the mountain of medical debt: stem cell therapies to ease suffering and save lives. We have the momentum. We dare not stop short. Chronic disease threatens everyone — we are fighting for your family, and mine!”

 

Using the courts to protect patients from unapproved stem cell therapies

A recent article in Nature looked at using lawsuits to help rein in the activities of clinics offering “unapproved” therapies. CIRM’s Geoff Lomax explains.

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When public health officials wanted to raise awareness about the dangers of smoking they filed lawsuits against the tobacco companies. They accused Big Tobacco of deceptive marketing and hiding the negative health effects of smoking. Ultimately, they won. Now a new study says a similar tactic could prove effective in combating clinics that offer unproven stem cell therapies.

CIRM works tirelessly to accelerate the delivery of stem cell treatments to patients with unmet medical needs. But, that doesn’t mean we support any treatment that claims to help people. CIRM only partners with projects that have been given the go-ahead by the US Food and Drug Administration (FDA) to be tested in people in a clinical trial.  That’s because FDA approval means the clinical trial will be monitored and evaluated under high scientific and ethical standards.

In contrast, there are numerous examples where “stem-cell treatments” not sanctioned by the FDA are being marketed directly to patients. For years the FDA, CIRM and others have been warning consumers about the risks involved with these untested treatments. For example, just last  November the FDA issued a warning and advice for people considering stem cell treatments.

Legal steps

Last year CIRM also helped author a new California law designed to protect consumers. The law requires health care providers to disclose to patients when using a treatment that is not FDA approved or part of an FDA-sanctioned clinical trial.

At CIRM, we frequently direct patients seeking treatments to our Alpha Stem Cell Clinics Network. The Alpha Clinics only perform clinical trials that have been given the green light by the FDA, and they provide expert consultation and informed consent to patients to help ensure they make the best choice for themselves. Further, the Alpha Clinics follow up with patients after their treatments to evaluate safety and the effectiveness of the treatments.

These are steps that clinics offering unproven and unapproved therapies typically don’t follow. So, the question is how do you let people know about the risks involved in going to one of these clinics and how do you stop clinics offering “therapies” that might endanger the health of patients?

Using the law to hit clinics where it hurts

In a recently published perspective in the journal Nature an international team of policy experts considered whether civil lawsuits may play a role in stemming the tide of unproven treatments. In the article the authors say:

“The threat of financial liability for wrongdoing is the primary means by which civil law governs behavior in the private sector. Despite calls for stepping up enforcement efforts, the US Food and Drug Administration (FDA) is currently restricted in its ability to identify and target clinics operating in apparent violation of regulations. The fear of tort liability {lawsuits} may provide sufficient incentive for compliance and minimize the occurrence of unethical practices.”

The authors identified nine individual and class action lawsuits involving clinics offering what they called “unproven stem cell interventions.” A few of those were dismissed or decided in favor of the clinics, with judges saying the claims lacked merit. Most, however, were settled by the clinics with no ruling on the merits of the issue raised. Even without definitive judgements against the clinics the authors of the article conclude:

“Stem cell lawsuits could intensify publicity and raise awareness of the harms of unproven treatments, set legal precedent, reshape the media narrative from one focused on the right to try or practice to one highlighting the need for adequate safety and efficacy standards, and encourage authorities to turn their attention to policy reform and enforcement.”

The authors suggest the courts may provide a forum where medical experts can inform patients, the legal community and the public about good versus harmful clinical practices. In short, the authors believe the legal process can be an effective forum for to provide education and outreach to those with disease and the public at large.

The better option of course would be for the clinics themselves to reform their practices and engage with the FDA to test their therapies in a clinical trial. Until that happens the courts may offer an alternative approach to curbing the marketing of these unproven and unapproved therapies.

How a tiny patch of skin helped researchers save the life of a young boy battling a deadly disease

 

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After receiving his new skin, the boy plays on the grounds of the hospital in Bochum, Germany. Credit: RUB

By any standards epidermolysis bullosa (EB) is a nasty disease. It’s a genetic condition that causes the skin to blister, break and tear off. At best, it’s painful and disfiguring. At worst, it can be fatal. Now researchers in Italy have come up with an approach that could offer hope for people battling the condition.

EB is caused by genetic mutations that leave the top layer of skin unable to anchor to inner layers. People born with EB are often called “Butterfly Children” because, as the analogy goes, their skin is as fragile as the wings of a butterfly. There are no cures and the only treatment involves constantly dressing the skin, sometimes several times a day. With each change of dressing, layers of skin can be peeled away, causing pain.

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Hands of a person with EB

Life and death for one boy

For Hassan, a seven-year old boy admitted to the Burn Unit of the Children’s Hospital in Bochum, Germany, the condition was particularly severe. Since birth Hassan had repeatedly developed blisters all over his body, but several weeks before being admitted to the hospital his condition took an even more serious turn. He had lost skin on around 80 percent of his body and he was battling severe infections. His life hung in the balance.

Hassan’s form of EB was caused by a mutation in a single gene, called LAMB3. Fortunately, a team of researchers at the University of Modena and Reggio Emilia in Italy had been doing work in this area and had a potential treatment.

To repair the damage the researchers took a leaf out of the way severe burns are treated, using layers of skin to replace the damaged surface. In this case the team took a tiny piece of skin, about half an inch square, from Hassan and, in the laboratory, used a retrovirus to deliver a corrected version of the defective gene into the skin cells.

 

They then used the stem cells in the skin to grow sizable sheets of new skin, ranging in size from about 20 to 60 square inches, and used that to replace the damaged skin.

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In the study, published in the journal Nature, the researchers say the technique worked quickly:

“Upon removal of the non-adhering gauze (ten days after grafting) epidermal engraftment was evident. One month after grafting, epidermal regeneration was stable and complete. Thus approximately 80% of the patient’s TBSA (total body surface area) was restored by the transgenic epidermis.”

The engrafted skin not only covered all the damaged areas, it also proved remarkably durable. In the two years since the surgery the skin has remained, in the words of the researchers, “stable and robust, and does not blister, itch, or require ointment or medications.”

In an interview in Science, Jakub Tolar, an expert on EB at the University of Minnesota, talked about the significance of this study:

“It is very unusual that we would see a publication with a single case study anymore, but this one is a little different. This is one of these [studies] that can determine where the future of the field is going to go.”

Because the treatment focused on one particular genetic mutation it won’t be a cure for all EB patients, but it could provide vital information to help many people with the disease. The researchers identified a particular category of cells that seemed to play a key role in helping repair the skin. These cells, called holoclones, could be an important target for future research.

The researchers also said that if a child is diagnosed with EB at birth then skin cells can be taken and turned into a ready-made supply of the sheets that can be used to treat skin lesions when they develop. This would enable doctors to treat problems before they become serious, rather than have to try and repair the damage later.

As for Hassan, he is now back in school, leading a normal life and is even able to play soccer.

 

 

CIRM weekly stem cell roundup: stomach bacteria & cancer; vitamin C may block leukemia; stem cells bring down a 6’2″ 246lb football player

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This is what your stomach glands looks like from the inside:  Credit: MPI for Infection Biology”

Stomach bacteria crank up stem cell renewal, may be link to gastric cancer (Todd Dubnicoff)

The Centers for Disease Control and Prevention estimate that two-thirds of the world’s population is infected with H. pylori, a type of bacteria that thrives in the harsh acidic conditions of the stomach. Data accumulated over the past few decades shows strong evidence that H. pylori infection increases the risk of stomach cancers. The underlying mechanisms of this link have remained unclear. But research published this week in Nature suggests that the bacteria cause stem cells located in the stomach lining to divide more frequently leading to an increased potential for cancerous growth.

Tumors need to make an initial foothold in a tissue in order to grow and spread. But the cells of our stomach lining are replaced every four days. So, how would H. pylori bacterial infection have time to induce a cancer? The research team – a collaboration between scientists at the Max Planck Institute in Berlin and Stanford University – asked that question and found that the bacteria are also able to penetrate down into the stomach glands and infect stem cells whose job it is to continually replenish the stomach lining.

Further analysis in mice revealed that two groups of stem cells exist in the stomach glands – one slowly dividing and one rapidly dividing population. Both stem cell populations respond similarly to an important signaling protein, called Wnt, that sustains stem cell renewal. But the team also discovered a second key stem cell signaling protein called R-spondin that is released by connective tissue underneath the stomach glands. H. pylori infection of these cells causes an increase in R-spondin which shuts down the slowly dividing stem cell population but cranks up the cell division of the rapidly dividing stem cells. First author, Dr. Michal Sigal, summed up in a press release how these results may point to stem cells as the link between bacterial infection and increased risk of stomach cancer:

“Since H. pylori causes life-long infections, the constant increase in stem cell divisions may be enough to explain the increased risk of carcinogenesis observed.”

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Vitamin C may have anti-blood cancer properties

Vitamin C is known to have a number of health benefits, from preventing scurvy to limiting the buildup of fatty plaque in your arteries. Now a new study says we might soon be able to add another benefit: it may be able to block the progression of leukemia and other blood cancers.

Researchers at the NYU School of Medicine focused their work on an enzyme called TET2. This is found in hematopoietic stem cells (HSCs), the kind of stem cell typically found in bone marrow. The absence of TET2 is known to keep these HSCs in a pre-leukemic state; in effect priming the body to develop leukemia. The researchers showed that high doses of vitamin C can prevent, or even reverse that, by increasing the activity level of TET2.

In the study, in the journal Cell, they showed how they developed mice that could have their levels of TET2 increased or decreased. They then transplanted bone marrow with low levels of TET2 from those mice into healthy, normal mice. The healthy mice started to develop leukemia-like symptoms. However, when the researchers used high doses of vitamin C to restore the activity levels of TET2, they were able to halt the progression of the leukemia.

Now this doesn’t mean you should run out and get as much vitamin C as you can to help protect you against leukemia. In an article in The Scientist, Benjamin Neel, senior author of the study, says while vitamin C does have health benefits,  consuming large doses won’t do you much good:

“They’re unlikely to be a general anti-cancer therapy, and they really should be understood based on the molecular understanding of the many actions vitamin C has in cells.”

However, Neel says these findings do give scientists a new tool to help them target cells before they become leukemic.

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Bad toe forces Jordan Reed to take a knee: Photo courtesy FanRag Sports

Toeing the line: how unapproved stem cell treatment made matters worse for an NFL player  

American football players are tough. They have to be to withstand pounding tackles by 300lb men wearing pads and a helmet. But it wasn’t a crunching hit that took Washington Redskins player Jordan Reed out of the game; all it took to put the 6’2” 246 lb player on the PUP (Physically Unable to Perform) list was a little stem cell injection.

Reed has had a lingering injury problem with the big toe on his left foot. So, during the off-season, he thought he would take care of the issue, and got a stem cell injection in the toe. It didn’t quite work the way he hoped.

In an interview with the Richmond Times Dispatch he said:

“That kind of flared it up a bit on me. Now I’m just letting it calm down before I get out there. I’ve just gotta take my time, let it heal and strengthen up, then get back out there.”

It’s not clear what kind of stem cells Reed got, if they were his own or from a donor. What is clear is that he is just the latest in a long line of athletes who have turned to stem cells to help repair or speed up recovery from an injury. These are treatments that have not been approved by the Food and Drug Administration (FDA) and that have not been tested in a clinical trial to make sure they are both safe and effective.

In Reed’s case the problem seems to be a relatively minor one; his toe is expected to heal and he should be back in action before too long.

Stem cell researcher and avid blogger Dr. Paul Knoepfler wrote he is lucky, others who take a similar approach may not be:

“Fortunately, it sounds like Reed will be fine, but some people have much worse reactions to unproven stem cells than a sore toe, including blindness and tumors. Be careful out there!”

Keeping intestinal stem cells in their prime

Gut stem cells (green) in the small intestine of a mouse.

The average length of the human gut is 25 feet long. That’s equivalent to four really tall people or five really short people lined up head to toe. Intestinal stem cells have the fun job of regenerating and replacing ALL the cells that line the gut. Therefore, it’s important for these stem cells to be able to self-renew, a process that replenishes the stem cell population. If this important biological process is disrupted, the intestine is at risk for diseases like inflammatory bowel disease and cancer.

This week, Stanford Medicine researchers published new findings about the biological processes responsible for regulating the regenerative capacity of intestinal stem cells. Their work, which was partially funded by CIRM, was published in the journal Nature.

Priming gut stem cells to self-renew

Scientists know that the self-renewal of intestinal stem cells is very important for a happy, functioning gut, but the nuances of what molecules and signaling pathways regulate this process have yet to be figured out. The Stanford team, led by senior author and Stanford Professor Dr. Calvin Kuo, studied two signaling pathways, Wnt and R-Spondin, that are involved in the self-renewal of intestinal stem cells in mice.

Dr. Calvin Kuo, Stanford Medicine.

“The cascade of events comprising the Wnt signaling pathway is crucial to stem cell self-renewal,” Dr. Kuo explained in an email exchange. “The Wnt pathway can be induced by either hormones classified as “Wnts” or “R-spondins”.  However, it is not known if Wnts or R-spondins cooperate to induce Wnt signaling, and if these Wnts and R-spondins have distinct functions or if they can mutually substitute for each other.   We explored how Wnts and R-spondins might cooperate to regulate intestinal stem cells – which are extremely active and regenerate the 25-foot lining of the human intestine every week.”

The team used different reagents to activate or block Wnt or R-spondin signaling and monitored the effects on intestinal stem cells. They found that both were important for the self-renewal of intestinal stem cells, but that they played different roles.

“Our work revealed that Wnts and R-spondins are not equivalent and that they have very distinct functions even though they both trigger the Wnt signaling cascade,” said Dr. Kuo. “Both Wnts and R-spondins are required to maintain intestinal stem cells.  However, Wnts perform more of a subservient “priming” function, where they prepare intestinal stem cells for the action of R-spondin, which is the active catalyst for inducing intestinal stem cells to divide.”

The authors believe that this multi-step regulation, involving priming and self-renewal factors could apply to stem cell systems in other organs and tissues in the body. Some of the researchers on this study including Dr. Kuo are pursuing this idea through a new company called Surrozen, which produces artificial bioengineered Wnt molecules that don’t require activation like natural Wnt molecules. These Wnt molecules were used in the current study and are explained in more detail in a separate Nature article published at the same time.

The company believes that artificial Wnts will be useful for understanding stem cell biology and potentially for therapeutic applications. Dr. Kuo explained,

“The new surrogate Wnts are easily produced and can circulate in the bloodstream, unlike natural Wnts.  There may be medical applications of these bioengineered Wnt surrogates in stimulating various stem cell compartments of the body, given the wide range of stem cells that are governed by natural Wnts.”

Pregnant women’s stem cells could help battle brittle bone diseases like osteoporosis

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Sometimes I wonder how a scientist ever came up with an idea for a potential treatment. Case in point is a study in the journal Scientific Reports, where researchers use stem cells from the amniotic fluid of a pregnant woman to cure osteoporosis in mice! What researcher, seeing a pregnant woman, thought to her or himself “I wonder if…..”

Regardless of how they came up with the idea, we might be glad they did because this study showed that those stem cells could reduce the number of fractures in mice with brittle bone disease by 78 percent. And that’s raising hopes they might one day be able to do the same for people.

Researchers at University College London took mesenchymal stem cells (MSCs) that had been shed by babies into the amniotic fluid of their mother, and injected them into mice with brittle bone disease. Previous studies had suggested that MSCs, taken at such an early age, might be more potent than similar cells taken from adults. That certainly seems to have been the case here where the treated mice had far fewer fractures than untreated mice.

Pascale Guillot, the lead researcher of the study, told the Guardian newspaper:

“The stem cells we’ve used are excellent at protecting bones. The bones become much stronger and the way the bone is organised internally is of much higher quality.”

 

What was also interesting was not just what they did but how they did it. You might think that the injected stem cells helped reduce fractures by forming new bones. You might think that, but you’d be wrong. Instead, the stem cells seem to have worked by releasing growth factors that stimulated the mouse’s own bone cells to kick into a higher gear, and help build stronger bones.

In the study the researchers say using MSCs from amniotic fluid has a number of distinct advantages over using MSCs from adults:

  • They are easier to expand into large numbers needed for therapies
  • They don’t create tumors
  • The body’s immune system won’t attack them
  • They are smaller and so can move around with greater ease
  • They are easier to reprogram into different kinds of cells

Next Guillot and his team want to explore if this approach could be used to treat children and adults with brittle bone disease, and to help adults with osteoporosis, a problem that affects around 44 million people in the US.

 “The discovery could have a profound effect on the lives of patients who have fragile bones and could stop a large number of their painful fractures.”

Failed stem cells may cause deadly lung disease

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Breathing is something we take for granted. It’s automatic. We don’t need to think about it. But for people with pulmonary fibrosis, breathing is something that is always on their minds.

Pulmonary fibrosis (PF) is a disease where the tissue in your lungs becomes thick and stiff, even scarred, making it difficult to breathe. It can be a frightening experience; and it doesn’t just affect your lungs.

Because your lungs don’t work properly they aren’t able to move as much oxygen as you need into your bloodstream, and that can have an impact on all your other organs, such as your brain and heart. There are some treatments but no cures, in large part because we didn’t know the cause of the disease. Many patients with PF live only 3-5 years after diagnosis.

Now a new CIRM-funded study from researchers at Cedars-Sinai has uncovered clues as to the cause of the disease, and that in turn could pave the way to new treatments.

The study, published in the journal Nature, found that a class of stem cells in the lung, called AEC2s, are responsible for helping repair damage caused by things such as pollution or infection. People who have PF have far fewer of these AEC2 cells, and those cells also had a much lower concentration of a chemical substance called hyaluronan, which is essential for repair damaged tissue.

They tested this theory with laboratory mice and found that by removing hyaluronan the mice developed thick scarring in their lungs.

In a news release from Cedars-Sinai Carol Liang, the study’s first author, said knowing the cause of the problem may help identify potential solutions:

“These findings are the first published evidence that idiopathic pulmonary fibrosis is primarily a disease of AEC2 stem cell failure. In further studies, we will explore how the loss of hyaluronan promotes fibrosis and how it might be restored to cell surfaces. These endeavors could lead to new therapeutic approaches.”

Knowing that a problem with AEC2 cells causes PF means the researchers can now start testing different medications to see which ones might help boost production of replacement AEC2 cells, or help protect those still functioning.