fat

Stem cell stories that caught our eye: How Zika may impact adult brains; Move over CRISPR there’s a new kid in town; How our bodies store fat

/ Kevin McCormack / Leave a comment

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.

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Zika mosquito

Zika virus could impact adult brains

It’s not just a baby’s developing brain that is vulnerable to the Zika virus, adult brains may be too. A new study shows that some stem cells that help repair damage in the adult brain can be impacted by Zika. This is the first time we’ve had any indication this could be a problem in a fully developed brain.

The study, in the journal Cell Stem Cell, looked at neural progenitors, a  stem cell that plays an important role in helping replace or repair damaged neurons, or nerve cells, in the brain. The researchers exposed the cells to the Zika virus and found that it infected the cells, causing some of the cells to die, and also limited the ability of the cells to proliferate.

In an interview in Healthday, Sujan Shresta, a researcher at the La Jolla Institute for Allergy and Immunology and one of the lead authors of the study, says although their work was done in adult mice, it may have implications for people:

“Zika can clearly enter the brains of adults and can wreak havoc. But it’s a complex disease, it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle and now we know what to look for.”

Move over CRISPR, there’s a new gene-editing tool in town

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Jennifer Lopez: Photo courtesy MTV

For much of the last year the hottest topic in stem cell and gene editing research has been CRISPR and the ease with which it can be used to edit genes. It’s so hot that apparently it’s the title of an upcoming TV show starring Jeniffer Lopez.

But hold on J-Lo, a new study in Nature Communications says by the time the show is on the air it may be old hat. Researchers at Carnegie Mellon and Yale University have developed a new gene-editing system, one they claim is easier to use and more accurate than CRISPR. And to prove it, they say they have successfully cured a genetic blood disorder in mice, using a simple IV approach.

Tools like CRISPR use enzymes to cut open sections of DNA to edit a specific gene. It’s like using a pair of scissors to cut a piece of string that has a big knot in the middle; you cut out the knot then join the ends of the string together. The problem with CRISPR is that the enzymes it uses are quite large and hard to use in a living animal – let alone a human – so they have to remove the target cells from the body and do the editing in the lab. Another problem is that CRISPR sometimes cuts sections of DNA that the researchers don’t want cut and could lead to dangerous side effects.

Greater precision

The Carnegie Mellon/Yale team say their new method avoids both problems. They use nanoparticles that contain molecules made from peptide nucleic acid (PNA), a kind of artificial form of DNA. This PNA is engineered to be able to cut open DNA and bind to a specific target without cutting anything else.

The team used this approach to target the mutated gene in beta thalassemia, a blood disorder that can be fatal if left untreated. The therapy binds to the malfunctioning gene, enabling the body’s own DNA repair system to correct the problem.

In a news story in Science Daily Danith Ly, one of the lead authors on the study, says even though the technique was successful in editing the target genes just 7 percent of the time, that is way more than the 0.1 percent rate most other gene editing tools achieve.

“The effect may only be 7 percent, but that’s curative. In the case of this particular disease model, you don’t need a lot of correction. You don’t need 100 percent to see the phenotype return to normal.”

Hormone that controls if and when fat cells mature

Obesity is one of the fastest growing public health problems in the US and globally. Understanding the mechanisms behind how that happens could be key to finding ways to address it. Now researchers at Stanford University think they may have uncovered an important part of the answer.

Their findings, reported in Science Signaling, show that mature fat cells produce a hormone called Adamts1 which acts like a switch for surrounding stem cells, determining if they change into fat-storing cells.   People who eat a high-fat diet experience a change in their Adamst1 production, and that triggers the nearby stem cells to specialize and start storing fat.

There are still a lot of questions to be answered about Adamst1, including whether it acts alone or in conjunction with other as yet unknown hormones. But in an article in Health Canal, Brian Feldman, the senior author of the study, says they can now start looking at potential use of Adamst1 to fight obesity.

“That won’t be a simple answer. If you block fat formation, extra calories have to go somewhere in the body, and sending them somewhere else outside fat cells could be more detrimental to metabolism. We know from other researchers’ work that liver and muscle are both bad places to store fat, for example. We do think there are going to be opportunities for new treatments based on our discoveries, but not by simply blocking fat formation alone.”

 

Stem cell stories that caught our eye: Designer bags from human skin, large-scale stem cell production, new look at fat stem cells

/ Karen Ring / Leave a comment

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.

Designer bags from human skin? I had to share a bizarre story I read this week about a UK fashion designer who is making a collection of luxury handbags from lab-grown human skin called Pure Human. What’s even weirder is that the human skin used was engineered to contain the genetic material or DNA of the famous fashion designer Alexander McQueen who passed away in 2010.

A prototype bag, made with pig skin, from Tina Gorjanc’s Pure Human collection (Credit: Tina Gorjanc)

A prototype bag, made with pig skin, from Tina Gorjanc’s Pure Human collection (Credit: Tina Gorjanc & Signals blog for caption)

I had to admit I cringed when I first read about it in CCRM’s Signals Blog, but now I am fascinated that someone is actually doing this and intrigued about the ethical conversations that this story will undoubtedly stir up.

While it isn’t possible to patent a person’s DNA, it is possible to patent a technology that uses human DNA and products made from that technology. According to Signals, “the aim of the collection is to highlight existing legal loopholes around ownership of a person’s DNA and to open the doors for tissue bioengineering into the world of fashion.”

The collection’s designer, Tina Gorjanc, explained her motivation behind Pure Human:

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Tina Gorjanc

“My main goal was to show that it is possible to patent a process using human genetic information in a domain other than medicine. Biotechnology is happening at a really rapid pace and legislation has not kept up with it.”

 

She also sees her bags as an untapped resource in the global luxury goods market which is now apparently worth $1 trillion dollars.

“When it comes to bioengineering, people tend to skip the luxury goods market because they think it’s too shallow and not important, but if you look at it, it’s one of the biggest markets that we have – and one that is open to new technology.”

Imagine having the option to bypass animal leather products for engineered human skin-based products? But on the flip side, the author of the Signals blog, Jovana Drinjakovic, makes a great point at the end of her piece by saying: just because we can do this, does it mean we should?

Drinjakovic finishes her piece with a reality-check quote from Dr. Marc Jeschke, the leader of a burn research and skin regeneration lab in Toronto:

“We are trying to find a way to make skin that is functional and won’t be rejected after a transplant. But just to grow skin for fashion – I don’t think that’s very useful.”

 

Large-Scale Stem Cell Production in Texas. A nonprofit company in San Antonio, Texas, called BioBridge, has big plans to produce large amounts of clinical-grade stem cells for regenerative medicine purposes. The company recently received $7.8 million in funding from the Medical Technology Enterprise Consortium to pursue this effort.

BioBridge will work with GenCure, a subsidiary company, to develop the technology to manufacture different types of stem cells at a large scale. These stem cells will be clinical-grade, meaning that they can be used for cell therapy applications in patients. BioBridge’s goal is to provide enough stem cells for both academic researchers and companies who need more than their current lab resources can generate.

The CEO of GenCure, Becky Cap, explained the need for this type of large-scale stem cell manufacturing technology in an interview with Xconomy:

“The capabilities in this sector right now are at a scale that’s appropriate for bench research and some clinical research, depending on the indication and volume of cells we need. We’re talking about moving from hundreds of millions of cells to billions of cells. You need billions of cells to do tissue regeneration and scaffold reengineering.”

Two other companies with expertise in cell manufacturing, StemBioSys from San Antonio and RoosterBio in Maryland, will be working with BioBridge and GenCure over the next three years on specific projects. StemBioSys plans to develop materials that will be used to promote stem cell growth. RoosterBio will take stem cell culturing from small-scale petri dishes to large-scale bioreactors that can produce billions of cells.

It will be interesting to see how the BioBridge collaboration works out. Xconomy concluded:

“This sort of large-scale manufacturing is still years out. The results that come from the work will be incorporated into a contract manufacturing operation that BioBridge is opening within GenCure.”

 

A new way to look at fat stem cells. (By Todd Dubnicoff)

Human fat stem cells, scientifically known as human adipose stem cells (hASC), are an attractive cell source for regenerative medicine. Their low tendency to cause tissue rejection and their ability to transform into bone cells make them particularly well-suited for developing cell-based treatments for osteoporosis, a disease that weakens bones and makes them susceptible to fractures. And thanks to the numerous liposuction procedures performed in the U.S. each year, hASCs are readily available to researchers.

Electron microscope image showing the eroded, inner structure of a back bone in an 89 year old woman with osteoposis. Image courtesy the Bone Research Society

Electron microscope image showing the eroded, inner structure of a back bone in an 89 year old woman with osteoposis. Image courtesy the Bone Research Society.

But a lingering problem with hASCs as a reliable cell source for future therapies is their extreme patient-to-patient variability. Studies have shown that all sorts of factors like gender, body mass index (BMI) and age can have profound effects on the ability of hASCs to multiply and to specialize into bone cells.

Now, University of Missouri researchers describe the novel use of a measuring device to make more quantitative comparisons of different sets of donor hASCs. The instrument, called an electrical cell-substrate impedance spectroscopy (ECIS) – try saying that three times fast! – sends a very weak, noninvasive current through the cells and can measure changes in the cells’ shape in real-time. Other studies had shown that ECIS can quantitatively detect differences between hASCs and human bone marrow-derived mesenchymal stem cells as they mature into their respective cell types.

In the current Stem Cells Translational Medicine study, picked up this week by Health Canal, hASCs were obtained from young (24–36 years old), middle-aged (48–55 years old), and elderly (60–81 years old) donors. The ECIS results showed that stem cells from older donors matured into bone cells much quicker (~ 1day) than the younger cell of cells (~10 day). You might have intuitively thought the youngest stem cells would mature the fastest. But the end result of the difference is that the young set of stem cells multiplied much more than the cells from older donor and they accumulated more calcium over time.

This noninvasive, quantitative tool for predicting a fat stem cell’s potential to specialize into bone has the promise to improve quality control for manufacturing cell therapies, and it also provides researchers a means to better observe the underlying biological basis for this patient-to-patient variability in human fat cells.

Finally a possible use for your excess fat; using it to fix your arthritic knee

/ Kevin McCormack / Leave a comment

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One of the most common questions we get asked at CIRM, almost every other day to be honest, is “are there any stem cell treatments for people with arthritis in their knees?” It’s not surprising. This is a problem that plagues millions of Americans and is one of the leading causes of disability in the US.

Sadly, we have to tell people that there are no stem cell treatments for osteoarthritis (OA) in the knee that have been approved by the Food and Drug Administration (FDA). There’s also a lack of solid evidence from clinical trials that the various approaches are effective.

But that could be changing. There’s a growing number of clinical trials underway looking at different approaches to treating OA in the knee using various forms of stem cells. Sixteen of those are listed at clinicaltrials.gov. And one new study suggests that just one injection of stem cells may be able to help reduce pain and inflammation in arthritic knees, at least for six months. The operative word here being may.

The study, published in the journal Stem Cells Translational Medicine,  used adipose-derived stromal cells, a kind of stem cell taken from the patient’s own fat. Previous studies have shown that these cells can have immune boosting and anti-scarring properties.

The cells were removed by liposuction, so not only did the patient’s get a boost for their knees they also got a little fat reduction. A nice bonus if desired.

The study was quite small. It involved 18 patients, between the ages of 50 and 75, all of whom had suffered from osteoarthritis (OA) in the knee for at least a year before the treatment. This condition is caused by the cartilage in the knee breaking down, allowing bones to rub against each other, leading to pain, stiffness and swelling.

One group of patients were given a low dose of the cells (23,000) injected directly into the knee, one a medium dose (103,000) and one a high dose (503,000).

Over the next six months, the patients were closely followed to see if there were any side effects and, of course, any improvement in their condition. In a news release, Christian Jorgensen, of University Hospital of Montpellier, the director of the study, said the results were encouraging:

“Although this phase I study included a limited number of patients without a placebo arm we were able to show that this innovative treatment was well tolerated in patients with knee OA and it provided encouraging preliminary evidence of efficacy. Interestingly, patients treated with low-dose ASCs significantly improved in pain and function compared with the baseline.”

The researchers caution that the treatment doesn’t halt the progression of OA and does not restore the damaged cartilage, instead it seems to help patients by reducing inflammation.

In a news article about the study Tony Atala, director of the Wake Forest Institute for Regenerative Medicine, in Winston-Salem, N.C. and the editor of Stem Cells Translational Medicine said the study offered the patients involved another benefit:

“In fact, most of the patients (in the study group) who had previously scheduled total knee replacement surgery decided to cancel the surgery. It will be interesting to see if these improvements are seen in larger groups of study participants.”

Interesting is an understatement.

But while this is encouraging it’s important to remember it was done in a small group of patients and needs to be replicated in a much larger group before we can draw any solid conclusions. It will also be important to see if the benefits last longer than six months.

We might not have to wait too long for some answers. The researchers are already running a 2-year trial involving 150 people in Europe.

We’ll let you know what they find.

 

New type of diabetes caused by old age may be treatable

/ Karen Ring / 8 Comments

I’m going to tell you a secret: I love sugar. I love it so much that as a little kid my mom used to tell me scary stories about how my teeth would fall out and that I might get diabetes one day if I ate too many sweets. Thankfully, none of these things happened. I have a full set of teeth (and they’re real), my blood sugar level is normal, and I’ve become one with the term “everything in moderation”.

I am not out of the woods, however: a newly discovered type of diabetes could strike in a few decades. A research team has found the cause of a type of diabetes that occurs because of old age, and a potential cure, at least in mice.

Diabetes comes in different flavors

People who suffer from diabetes (which is almost 30 million Americans) lack the ability to regulate the amount of sugar in their blood. The pancreas is the organ that regulates blood sugar by producing a hormone called insulin. If blood has a high sugar level, the pancreas releases insulin, which helps muscle, liver, and fat cells to absorb the excess sugar until the levels in the blood are back to normal.

There are two main forms of diabetes, type 1 and 2, both of which cause hyperglycemia or high blood sugar. Type 1 is an autoimmune disorder where the immune system attacks and kills the insulin-producing cells in the pancreas. As a result, these type 1 diabetics aren’t able to produce insulin and endure a lifetime of daily insulin shots to manage their condition. Type 2 diabetes is the more common form of the disease and occurs when the body’s cells become unresponsive, or resistant, to insulin and stop absorbing sugar from the bloodstream.

The cause of type 1 diabetes is not known although genetic factors are sure to be involved. Type 2 diabetes can be caused by a combination of factors including poor diet, obesity, genetics, stress, and old age. Both forms of the disease can be fatal if not managed properly and raise the risk of other medical complications such as heart disease, blindness, ulcers, and kidney failure.

While type 1 or 2 diabetes make up the vast majority of the cases, there are actually other forms of this disease that we are only just beginning to understand. One of them is type 3, which is linked to Alzheimer’s disease. (To learn more about the link between AD and diabetes, read this blog.)

Old age can cause diabetes

Another form of diabetes, which is in the running for the title of type 4, is caused by old age. Unlike type 2 diabetes which also occurs in adults, type 4 individuals don’t have the typical associated risk factors like weight gain. The exact mechanism behind age-related type 4 diabetes in humans isn’t known, but a CIRM-funded study published today in Nature identified the cause of diabetes in older, non-obese mice.

Scientists from the Salk Institute compared the immune systems of healthy mice to lean mice with age-associated insulin resistance or mice with obesity-associated insulin resistance (the equivalent to type 2 diabetes in humans). When they studied the fat tissue in the three animal models, they noticed a striking difference in the number of immune cells called T regulatory cells (Tregs). These cells are the “keepers of the immune system”, and they keep inflammation and excessive activity of other immune cells to a minimum.

Lean mice with age-related diabetes, had a substantially larger number of Tregs in their fat tissue compared to obesity-related diabetic and normal mice. Instead of being their usual helpful selves, the overabundance of Tregs in the age-related diabetic mice caused insulin resistance.

Salk researchers show that diabetes in elderly, lean animals is caused by an overabundance of immune cells in fat. In this graphic, fat tissue is shown with representations of the immune cells called Tregs (orange). In aged mice with diabetes (represented on the right), Tregs are overexpressed in fat tissue and trigger insulin resistance. When Tregs are blocked, the fat cells in mice become insulin sensitive again. (Image courtesy of Salk Institute)

Diabetes in elderly, lean animals is caused by an overabundance of immune cells called Tregs (orange)  in fat tissue (brown cells). In aged mice with diabetes (right), Tregs are overexpressed in fat tissue and trigger insulin resistance. When Tregs are blocked, the fat cells in mice become insulin sensitive again. (Image courtesy of Salk Institute)

In a Salk Institute press release, lead author Sagar Bapat explained:

Normally, Tregs help calm inflammation. Because fat tissue is constantly broken down and built back up as it stores and releases energy, it requires low levels of inflammation to constantly remodel itself. But as someone ages, the new research suggests, Tregs gradually accumulate within fat. And if the cells reach a tipping point where they completely block inflammation in fat tissue, they can cause fat deposits to build up inside unseen areas of the body, including the liver, leading to insulin resistance.

A cure for type 4 diabetes, but in mice…

After they identified the cause, the authors next searched for a solution. They blocked the build up of Tregs in the fat tissue of age-related diabetic mice using an antibody drug that inhibits the production of Tregs. The drug successfully cured the age-related diabetic mice of their insulin resistance, but didn’t do the same for the obesity-related diabetic mice. The authors concluded that the two forms of diabetes have different causes and type 4 can be cured by removing excessive Tregs from fat tissue.

This study is only the beginning for understanding age-related diabetes. The authors next want to find out why Tregs accumulate in the fat tissue of older mice, and if they also build up in other tissues and organs. They are also curious to know if the same phenomenon happens in elderly humans who become diabetic but don’t have type 2 diabetes.

Understanding the cause of age-related diabetes in humans is of upmost importance to Ronald Evans who is the director of the Gene Expression Lab at the Salk Institute, and senior author on the study.

Ron Evans

Ron Evans

A lot of diabetes in the elderly goes undiagnosed because they don’t have the classical risk factors for type 2 diabetes, such as obesity. We hope our discovery not only leads to therapeutics, but to an increased recognition of type 4 diabetes as a distinct disease.

For more on this exciting study, check out a video interview of Dr. Evans from the Salk Institute:

Related links:

What’s Fat Got to do With Alzheimer’s?

/ Karen Ring / Leave a comment
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(Image credit: FineCooking.com)

Diets these days are a dime a dozen, and dietary trends come and go. First eggs were “out” because they contain cholesterol, but now they are back “in” because we now know that some types of cholesterol can be actually good for the body. Then there was the era of “fat-free” or “reduced-fat” foods. This was all the rage in the 90s until scientists realized that eliminating healthy fats from your diet can have negative consequences on your health.

The theories behind different diets evolve constantly much like the theories behind complicated neurodegenerative diseases like Alzheimer’s disease (AD). Alzheimer’s is a debilitating disease that slowly robs patients of their minds, leaving them as shadows of their former selves. AD affects 47.5 million people globally with 7.7 million new patients diagnosed every year, thus making the disease one of the most important unmet medical needs to be addressed.

The causes of AD have eluded scientists for over a century. However, the main theory behind what causes AD involves the buildup of toxic proteins in the brain. These proteins accumulate to form structures called plaques and tangles that impair brain function and kill off brain cells.

Unfortunately, there is no cure for AD or treatments to stop its progression. This sobering fact is not due to a lack of effort by scientists and pharmaceutical companies. Dozens of drug therapies have or are being tested in clinical trials, many of them focusing on the removal of toxic protein levels in people with the disease. While there have been some pretty dramatic failures in these trials, a few are starting to show encouraging results.

Link Between Abnormal Fat Metabolism and Alzheimer’s Disease

Now, a new theory on AD involving the build up of toxic fat molecules in the brains of AD patients has been thrown into the mix. In a study published Thursday in Cell Stem Cell, scientists from Montreal reported the presence of fat droplets in AD patient brains in areas surrounding brain stem cells. Brain stem cells are responsible for growing new brain cells (such as nerves) and maintaining overall brain function and health. The scientists discovered that the fat droplets actually prevented the regenerative abilities of the brain stem cells, leading them to believe that the accumulation of fat droplets in the brain could be a cause of AD.

Fat is used as an energy source by cells and organs in the body in a process called “fatty acid metabolism”. Fat metabolism is very important for proper brain development but also in maintaining brain health and function in adults. Problems with fat metabolism in humans can cause diseases such as obesity, diabetes, and heart disease. So one can imagine that problems with fat metabolism in the brain could also have serious consequences.

In this study, scientists used a genetic mouse model of AD that had a “triple-threat” of genetic mutations that cause AD in humans. They studied the brain stem cells in these mice and found that the support cells surrounding the stem cells were full of fat droplets. They also noticed that when the fat droplets were present, the brain stem cells were not dividing to generate new brain cells (which is a common defect associated with AD). When they looked at brain tissue from nine AD patients, they also observed a similar pattern of an increased concentration of fat droplets surrounding areas of brain stem cells compared to healthy human brain tissue.

fat droplets

AD patient brains (lower panel) have more fat droplets shown in red than normal healthy brains (upper panel). (Hamilton et al., 2015)

Using a fancy science technique called mass spectrometry, the scientists found that the fat droplets were made up of a fat triglyceride called oleic acid, which is a common component of vegetable and animal fats. To prove that oleic acid was bad for brain stem cells, they took normal healthy mice and injected oleic acid into their brains. They observed that adding this fat negatively affected the stem cells’ regenerative ability to divide. Going one step further, the scientists used drugs to block the formation of oleic acid in their AD mouse model, and saw that removing this fat allowed the brain stem cells to divide and function properly.

The major conclusions generated from this study were summarized nicely by senior author Karl Fernandes in a news release:

We discovered that these fatty acids are produced by the brain, that they build up slowly with normal aging, but that the process is accelerated significantly in the presence of genes that predispose to Alzheimer’s disease. In mice predisposed to the disease, we showed that these fatty acids accumulate very early on, at two months of age, which corresponds to the early twenties in humans. Therefore, we think that the build-up of fatty acids is not a consequence but rather a cause or accelerator of the disease.

 

Don’t Count Your Chickens Just Yet

While this study suggests that fat accumulation in the brain is a cause of AD, more research will need to be done to confirm that abnormal fat metabolism is the culprit. Some experiments can be done quickly such as treating their AD mouse model with the drugs that block the formation of the “bad fat” and monitoring them for an extended time period to see if blocking oleic acid accumulation prevents the onset of AD symptoms like memory loss. Other experiments, such as therapeutically targeting abnormal brain fat deposits in human, will be more long term projects with unknown results.

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Dr. Alois Alzheimer

Nontheless, this study nicely ties back to an observation by Dr. Alois Alzheimer who first reported about AD in 1906 . When he dissected the brains of AD patients who had passed away, he found five major pathologies that distinguished their brains from healthy brains. One of these traits was an increased concentration of fat droplets. Thus findings from Fernandes and his group revive a century old notion that fat metabolism could be a cause of AD and open doors for the development of new therapeutic strategies to fight AD.

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Stem cell stories that caught our eye; progress toward artificial brain, teeth may help the blind and obesity

/ Don Gibbons / 3 Comments

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.

More progress toward artificial brain. A team at the RIKEN Institute in Japan has used stem cells in a 3-D culture to create brain tissue more complex than prior efforts and from an area of the brain not produced before, the cerebellum—that lobe at the lower back of the brain that controls motor function and attention. As far back as 2008, a RIKEN team had created simple tissue that mimicked the cortex, the large surface area that controls memory and language.

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The Inquisitr web portal wrote a feature on a wide variety of efforts to create an artificial brain teeing off of this week’s publication of the cerebellum work in Cell Reports. The piece is fairly comprehensive covering computerized efforts to give robots intelligence and Europe’s Human Brain Project that is trying to map all the activity of the brain as a starting point for recapitulating it in the lab.

The experts interviewed included Robert Caplan of Tufts University in Massachusetts who is using 3-D scaffolding to build functional brain tissues that can process electrical signals. He is not planning any Frankenstein moments; he hopes to create models to improve understanding of brain diseases.

“Ideally we would like to have a laboratory brain system that recapitulates the most devastating diseases. We want to be able to take our existing toolkit of drugs and understand how they work instead of using trial and error.”

Teeth eyed as source of help for the blind. Today the European Union announced the first approval of a stem cell therapy for blindness. And already yesterday a team at the University of Pittsburg announced they had developed a new method to use stem cells to restore vision that could expand the number of patients who could benefit from stem cell therapy.

Many people have lost part or all their vision due to damage to the cornea on the surface of their eye. Even when they can gain vision back through a corneal transplant, their immune system often rejects the new tissue. So the ideal would be making new corneal tissue from the patient’s own cells. The Italian company that garnered the EU approval does this in patients by harvesting some of their own cornea-specific stem cells, called limbal stem cells. But this is only an option if only one eye is impacted by the damage.

The Pittsburgh team thinks it may have found an unlikely alternative source of limbal cells: the dental pulp taken from teeth that have be extracted. It is not as far fetched at it sounds on the surface. Teeth and the cornea both develop in the same section of the embryo, the cranial neural crest. So, they have a common lineage.

The researchers first treated the pulp cells with a solution that makes them turn into the type of cells found in the cornea. Then they created a fiber scaffold shaped like a cornea and seeded the cells on it. Many steps remain before people give up a tooth to regain their sight, but this first milestone points the way and was described in a press release from the journal Stem Cells Translational Medicine, which was picked up by the web site ClinicaSpace.

CIRM funds a project that also proposes to use the patient’s own limbal stem cells but using methods more likely to gain approval of the Food and Drug Administration than those used by the Italian company.

Stem cells and the fight against obesity. Of the two types of stem cells found in your bone marrow, one can form bone and cartilage and, all too often, fat. Preventing these stem cells from maturing into fat may be a tool in the fight against obesity according to a team at Queen Mary University of London.

The conversion of stem cells to fat seems to involve the cilia, or hair-like projections found on cells. When the cilia lengthen the stem cells progress toward becoming fat. But if the researchers genetically prevented that lengthening, they stopped the conversion to fat cells. The findings opens several different ways to think about understanding and curbing obesity says Melis Dalbay one of the authors of the study in a university press release picked up by ScienceNewsline.

“This is the first time that it has been shown that subtle changes in primary cilia structure can influence the differentiation of stem cells into fat. Since primary cilia length can be influenced by various factors including pharmaceuticals, inflammation and even mechanical forces, this study provides new insight into the regulation of fat cell formation and obesity.”

Stem cell stories that caught our eye: need for mature fat, Down syndrome, autism and those sweet pup faces

/ Don Gibbons / Leave a comment

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.

Embryonic stem cells and that sweet puppy face. Could altered stem cells give our pups those floppy ears and adorable faces? Research from Humboldt University in Berlin suggests that is the case. They speculate that when people began to domesticate wild animals they were unwittingly breeding for smaller adrenal glands that are responsible for the “fight-or-flight” syndrome. But those glands arise from a group of stem cells in the developing embryo, the neural crest, that is also responsible for many other aspects of the animal including parts of the skull and the ears.

Annika, a member of the author's "pack," shows the floppy ears and narrow face of domestication. The seat on the furniture could be another clue.

Annika, a member of the author’s “pack,” shows the floppy ears and narrow face of domestication. The seat on the furniture could be another clue.

Researchers have noted since Darwin’s time that these signs of “domestication syndrome” with its floppy ears and narrow faces carry across a broad range of domestic animals. The German team said that the genetic alterations of neural crest stem cells could explain this “hodge-podge of traits.”

The research was published in the journal Genetics and got wide pick up with a fun piece on Mashable and a bit more detail about the science in Pacific Standard Magazine.

Stress might make fat go rogue. It is not something dieters will want to hear, but in order to stay healthy your fat stem cells need to mature into adult fat tissue. When they don’t fat can accumulate at high levels in the bloodstream and within existing cells. A team at Boston University suggests that stress plays a role in how the body processes fat by inhibiting the maturation of fat stem cells. They identified two proteins that act as relay switches to regulate the fat stem cells. That signaling pathway now becomes a target for discovering drugs that might improve our handling of fat, even in times of stress. The team published their work in the Journal of Biological Chemistry and HealthCanal picked up the university’s press release.

Support cells linked to Down syndrome. CIRM-funded researchers at the University of California, Davis have found that the errors in nerve development in Down syndrome may be caused by abnormal functioning of the cells that are supposed to support them, the glial cells. The team started by reprogramming skin cell samples from people with Down syndrome into iPS type stem cells. They then matured those cells in two batches, one into neurons and one into glial cells. The nerves did not seem different from normal nerves but the glial cells produced an abnormally high level of a particular protein. When they mixed the two cell types together, that protein appeared to kill off part of the nerves.

What is intriguing, when they treated the mixed cells with a simple antibiotic the nerve damage did not occur. If the protein only has its negative impact on the developing brain, the finding opens up the possibility of preventive treatment for women who find their fetus has the third chromosome distinctive of Down syndrome. The researchers published their findings in Nature Communication and Science Daily ran a story on the work.

Pros and cons of the large autism trial. Using stem cells to try to treat autism provokes a lot of raw emotion in our field. I frequently field questions from desperate mothers wanting to know where they can take the umbilical cord stem cells they have stored in a freezer to treat their child with autism. I tell them about some of the controversies about this treatment and the need for more data before we know how to use the cells right, if there is any chance they can help at all. The Simons Foundation Autism Research Initiative published a well-balanced analysis of the first large clinical trial trying to answer those questions.

The piece has a skeptic rightfully noting that the type of stem cells in cord blood cannot make replacement cells for the poorly functioning nerve cells in people with autism. It also discusses the possibility that those stem cells might stimulate the person’s own cells to make some of the needed repairs. The trial, which will randomly assign patients to stem cell therapy or no therapy, is being led by Duke University’s Joanne Kurtzenburg, who is described by one outside expert as “the right person to do this.” She is a well-known leader in the field and I would love to have some data to share with parents.

CIRM hosted a group of international experts in autism to look at ways stem cells could foster therapies in autism that produced this report. One of the main suggestions was to use iPS type stem cells to model the disease as shown in this video.

Don Gibbons