Stories of Hope: Alzheimer’s Disease

This week on The Stem Cellar we feature some of our most inspiring patients and patient advocates as they share, in their own words, their Stories of Hope.

Adele Miller knew what came next. She had lived it twice already: her father’s unraveling, due to Alzheimer’s disease, and, a few years later, her mother’s journey through the same erasure of mind and memory. So when doctors told her, at age 55, that she, too, had the disease, she remembered her parents’ difficult last years.

Lauren Miller has seen first hand how Alzheimer's can erase a lifetime's worth of memories.

Lauren Miller has seen first hand how Alzheimer’s can erase a lifetime’s worth of memories.

‘Tell no one,’ she told her family. Keep it secret.

“She was ashamed,” her daughter, actress and writer Lauren Miller, recalls. “She was so embarrassed because there’s such a stigma.” And she worried about her family. How would they handle all this? “I asked her once if she was scared,” Lauren says. “She said she wasn’t afraid for herself. But she was afraid for me, and my dad, and my brother. She knew what she’d gone through with her parents.”

Alzheimer’s disease has been a constant in the actress’s family. Perhaps that made her more attuned to the subtle changes that can herald the onset of the disease. At Lauren’s college graduation, she saw the first clues that something was amiss with her mother. She was repeating herself. Not just, “Oh, have I told you this before?” This was different. A few years later, as she and her mother prepared for a party, Lauren was stunned by the changes in her mother’s behavior. Her mother’s memory no longer seemed to function. She kept forgetting that the taco salad was vegetarian. She kept asking over and over where to throw the garbage. Lauren knew that’s not like her mother, a teacher for 35 years. So she sat down with her brother Dan and their dad. It was time to do something for Mom.

“It’s not that my dad wasn’t noticing things. But I don’t think he wanted to admit there was a problem. And he was simply too close to it,” Lauren says.

It took less than five years for Alzheimer’s disease to rob Adele Miller of nearly everything. Before she turned 60, she couldn’t write. She couldn’t speak. She didn’t even recognize her family.

The loss, the sadness, and the anger that Alzheimer’s families feel is compounded by a sense of utter helplessness against a disease that yields to no drug. But Lauren decided she would not be helpless, and in 2011, she and her husband, actor Seth Rogen, launched Hilarity for Charity, which aims to raise Alzheimer’s awareness in young people while also raising funds for the Alzheimer’s Association. This year Hilarity for Charity sponsored its first college fundraisers. It also hosts support groups for under-40 caregivers.

“Seth has the ability to reach an audience that may not know much about Alzheimer’s. His fans are 16 year old boys who aren’t generally the target for Alzheimer’s awareness,” Lauren said. “But he was able to strike a cord with a lot of these young people. We get emails from people who are 16. ‘Thank you for doing this. I felt alone. Now there’s a voice.’ This is considered an old person’s disease, but it’s really not. It affects everyone.”

In December 2013, Lauren, co-writer, producer and star of For a Good Time, Call, joined the CIRM governing Board, the Independent Citizens Oversight Committee, as a patient advocate for Alzheimer’s disease.

“Alzheimer’s research is woefully underfunded by the government, so it’s important to have bold, innovative approaches like CIRM’s to take research to the next level,” Lauren said. “Stem cell research is at the cusp of something life changing. To me, it’s one of the things closest to making a step toward treatment. I jumped at the opportunity to be part of it.”

For information about CIRM-funded Alzheimer’s disease research, visit our Alzheimer’s Fact Sheet. You can read more about Lauren’s Story of Hope on our website.

FDA gives Asterias green light to start CIRM-funded clinical trial in spinal cord injury

This morning Asterias Biotherapeutics announced that they have been cleared by the Food and Drug Administration (FDA) to start a clinical trial using stem cells to treat spinal cord injury. It’s great news, doubly so as we are funding that trial.

1773071

You can read more about the trial in a news release we just sent out.

This trial is a follow-on to the Geron trial that we funded back in 2010 that was halted after 5 patients, not because of any safety concerns but because of a change in Geron’s business strategy.

Katie Sharify was the fifth and final patient enrolled in that trial and treated with the stem cells. Like all of us she was disappointed when the trial was halted. And like all of us she is delighted that Asterias is now taking that work and building on it.

Here’s what Katie had to say when she heard the news:

“Of course, I’m very happy that the trial has been revived. Knowing that the FDA approved the continuation based on the safety data I was a part of is great news. As you know, the trial was halted 2 days before I received the stem cells. A big part of why I ended up participating was because I figured that once the study is revived a bigger sample size (even if just by 1 person) was more valuable than a smaller one. I never regretted my choice to participate but I have doubted whether my contribution actually meant anything. I think now I finally feel a sense of accomplishment because the trial is not only being continued but also progressing in the right direction as a higher dose is going to be used. A lot remains unknown about human embryonic stem cells and that’s exactly why this research is so important. The scientific community is going to have a much greater understanding of these stem cells from the data that will be collected throughout the study and I’m glad to have been a part of this advancement.”

Building a Blueprint for the Human Brain

How does a brain blossom from a small cluster of cells into nature’s most powerful supercomputer? The answer has long puzzled scientists, but with new advances in stem cell biology, researchers are quickly mapping the complex suite of connections that together make up the brain.

UCLA scientists have developed a new system that can map the development of brain cells.

UCLA scientists have developed a new system that can map the development of brain cells.

One of the latest breakthroughs comes from Dr. Daniel Geschwind and his team at the University of California, Los Angeles (UCLA), who have found a way to track precisely how early-stage brain cells are formed. These findings, published recently in the journal Neuron, shed important light on what had long been considered one of biology’s black boxes—how a brain becomes a brain.

Along with co-lead authors and UCLA postdoctoral fellows Drs. Luis de la Torre-Ubieta and Jason Stein, Geschwind developed a new system that measures key data points along the lifetime of a cell, as it matures from an embryonic stem cell into a functioning brain cell, or neuron. These new data points, such as when certain genes are switched on and off, then allow the team to map how the developing human fetus constructs a functioning brain.

Geschwind is particularly excited about how this new information can help inform how complex neurological conditions—such as autism—can develop. As he stated in a news release:

“These new techniques offer extraordinary promise in the study of autism, because we now have an unbiased and genome-wide view of how genes are used in the development of the disease, like a fingerprint. Our goal is to develop new treatments for autism, and this discovery can provide the basis for improved high-efficiency screening methods and open up an enormous new realm of therapeutic possibilities that didn’t exist before.”

This research, which was funded in part by a training grant from CIRM, stands to improve the way that scientists model disease in a dish—one of the most useful applications of stem cell biology. To that end, the research team has developed a program called CoNTEXT that can identify the maturity levels of cells in a dish. They’ve made this program freely available to researchers, in the hopes that others can benefit. Said de la Torre-Ubieta:

“Our hope is that the scientific community will be able to use this particular program to create the best protocols and refine their methods.”

Want to learn more about how stem cell scientists study disease in a dish? Check out our pilot episode of “Stem Cells in your Face.”

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.

A Cool New Way of Raising Funds and Awareness

Raising money to help fight a disease is tough. Trying to raise awareness about the disease can be just as tough. Doing both together is positively masochistic; an experience that is often as rewarding as dumping a bucket of ice cold water over your head.

Have you taken the ALS Ice Bucket Challenge?

Have you taken the ALS Ice Bucket Challenge?

And that’s precisely what a growing number of people around the country are doing to raise awareness about—and money for research into—Amyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig’s disease. They are dumping buckets of ice-cold water on their head.

It’s called, not surprisingly, the Ice Bucket Challenge. The idea behind it is simple. You dare someone you know to dump a bucket of ice cold water over their head within the next 24 hours or make a donation to help fight ALS. Once the person you have challenged either completes the challenge or makes a donation they then challenge other people—usually three other people—to do the same. And of course there’s nothing stopping you both dumping the water on yourself and making a donation.

The idea started out with people who had ALS and their friends and family but it has quickly spread. Celebrities such as Facebook’s Mark Zuckerberg, singer/actor Justin Timberlake, TV newsman Matt Lauer and even New Jersey Governor Chris Christie have all taken the Challenge. In fact the campaign has gone viral with videos and pictures of people taking the Challenge popping up on social media – Facebook and Instagram in particular – at a bewildering rate.

It’s more than just an opportunity to laugh at a potential Presidential candidate taking a self-inflicted cold shower it’s also raising a ton of money. The ALS Association says it raised $4 million in donations between the end of July and August 12th. That’s more than three and a half times more than it raised during the same period last year. They have also added more than 70,000 new donors to their cause.

That money goes to research into finding new treatments for ALS because right now there is no effective therapy at all. It also goes to help people living with this nasty, debilitating and ultimately deadly disease.

In a blog on the ALS website Barbara Newhouse, the President and CEO of the ALS Association said:

“We have never seen anything like this in the history of the disease. We couldn’t be more thrilled with the level of compassion, generosity and sense of humor that people are exhibiting as they take part in this impactful viral initiative.”

What I love about this is not just that it is raising awareness and funds for a truly worthwhile cause but that it also shows how a little bit of creativity can create so much more interest in a disease, and the people suffering from it, than any amount of well-meaning, more traditional attempts at education.

At the Stem Cell Agency we have worked closely with our friends in the ALS Association for many years and they do terrific work (you can read about our funding on our ALS Fact Sheet). But it’s a relatively rare condition – only affecting some 30,000 people in the U.S. at any one time – so it always struggles to get people’s attention compared to bigger diseases such as Alzheimer’s or stroke. But with this campaign they have changed that. They have taken a simple idea, a simple challenge, and used it to open people’s eyes to what they can do to help fight back against a deadly disease.

I find that really refreshing. As refreshing as a bucket of water over my own head.

Kevin McCormack

Blood Test Reveals Alzheimer’s Disease Risk, CIRM-Funded Study Finds

Could a simple blood test predict your risk for one day developing Alzheimer's disease?

Could a simple blood test predict your risk for developing one day developing Alzheimer’s disease?

By the time someone begins to experience the clinical symptoms of Alzheimer’s disease, the damage has already been done. An accumulation of toxic proteins is causing brain cells to whither and die, taking with them a lifetime of precious memories.

But what if we had a definitive test that could predict one’s risk of developing Alzheimer’s, even before the onset of symptoms? Could we use it to develop an early-detection method and—even more importantly—a way to slow or halt the disease before it is too late?

While this may seem closer to fiction than reality, scientists from the Western University of Health Sciences are reporting that they’ve done just that: a simple blood test that can accurately predict one’s Alzheimer’s risk—up to ten years before symptoms begin to develop.

Reporting in the latest issue of Translational Psychiatry, senior author Dr. Doug Ethell and his research team describe their ingenious method of tracking the earliest stages of Alzheimer’s via a simple blood test.

Their test, called the CD4see assay, tracks the body’s early immune response to toxic proteins—called amyloid beta proteins—that accumulate and form harmful plaques in the brains of Alzheimer’s patients.

Ethell has long been studying how a class of immune cells, called T cells, responds to the buildup of amyloid beta. Previously, he showed that these so-called amyloid beta-specific T cells could actually counter the cognitive decline seen in Alzheimer’s. So, lower amyloid T cell levels should correlate with symptoms. As he explained in an interview:

“If our mouse studies were correct, then there should be fewer of those cells in Alzheimer’s patients. Translating those studies from mouse to man was going to take a big effort—characterizing the small proportion of T cells that respond to amyloid-beta from the millions of other kinds of T cell would require technology that didn’t exist yet.”

So Ethell turned to stem cells. With support from CIRM, Ethell and his team took human embryonic stem cells (hESCs) and developed a type of immune system cell called dendritic cells. These cells stimulated the growth of amyloid-beta T cells—effectively bringing them out of hiding and allowing the researchers to locate and count them.

“Everyone showed a decrease in these T cells as they aged, but the decline occurred earliest in women with the apoE4 gene (the single greatest genetic risk factor for Alzheimer’s), often right around the same time as menopause,” explained Ethell. “When our raw data was pasted on foam boards all over my office it seemed to us that older women had lower responses than men, and when the data was finally plotted the dramatic decline around menopause was clear.”

Interestingly, this observation seems to correlate with the fact that Alzheimer’s is more prevalent in women than in men.

Ethell and his team propose that the CD4see assay could soon be used to measure amyloid-beta-specific T cells against one’s age, sex and whether they carry apoE4. This could then be used to calculate the individual’s risk for developing Alzheimer’s symptoms in the future.

This assay could also prove helpful when looking to test new therapeutic strategies that treat early-stage Alzheimer’s—something that has proven difficult without a reliable early detection method.

“Alzheimer’s disease is a puzzle and every bit of knowledge adds a new piece,” added Ethell. “We now view Alzheimer’s disease very differently than we did even just a few years ago.”

Stem Cell Stories that Caught our Eye: Multiple Sclerosis, Parkinson’s and Reducing the Risk of Causing Tumors

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.

Cell therapy for Parkinson’s advancing to the clinic. A decade-long moratorium on the transplant of fetal nerve tissue into Parkinson’s patient will end in two months when the first patients in a large global trial will receive the cells. BioScience Technology did a detailed overview on the causes for the moratorium and the optimism about the time being right to try again. The publication also talks about what most people in the field believe will be the long-term solution: moving from scarce fetal tissue to nerve cells grown from readily available embryonic stem cells. The author’s jumping off point was a pair of presentations at the International Society for Stem Cell Research in June, which we wrote about at the time. But the BioScience piece provides more background on the mixed results of earlier studies and references to recent journal publications showing long term—as much as 20 year—benefit for some of those patients.

It goes on to describe multiple reasons why, once the benefit is confirmed with fetal cells, moving to stem cells might be the better way to go. Not only are they more readily available, they can be purified in the lab as they are matured into the desired type of early-stage nerve cell. Researchers believe that some of the side effects seen in the early fetal trials stemmed from the transplants containing a second type of cell that caused jerking movements known as dyskinesias. One stem cell trial is expected to start in 2017, which we discussed in June.

Immunity persists through a special set of stem cells. Our immune system involves so many players and so much cell-to-cell interaction that there are significant gaps in our understanding of how it all works. One of those is how we can have long-term immunity to certain pathogens. The T-cells responsible for destroying invading bugs remember encountering specific ones, but they only live for a few years, generally estimated at five to 15. The blood-forming stem cells that are capable of generating all our immune cells would not have memory of specific invaders so could not be responsible for the long term immunity.

Now, an international team from Germany and from the Hutchison Center in Washington has isolated a subset of so-called “memory T-cells” that have stem cell properties. They can renew themselves and they can generate diverse offspring cells. Researchers have assumed cells like this must exist, but could not confirm it until they had some of the latest gee-wiz technologies that allow us to study single cells over time. ScienceDaily carried a story derived from a press release from the university in Munich and it discusses the long-term potential benefits from this finding, most notably for immune therapies in cancer. The team published their work in the journal Immunity.

Method may reduce the risk of stem cells causing tumors. When teams think about transplanting cells derived from pluripotent stem cells, either embryonic or iPS cells, they have to be concerned about causing tumors. While they will have tried to mature all the cells into a specific desired adult tissue, there may be a few pluripotent stem cells still in the mix that can cause tumors. A team at the Mayo Clinic seems to have developed a way to prevent any remaining stem cells in transplants derived from iPS cells from forming tumors. They treated the cells with a drug that blocks an enzyme needed for the stem cells to proliferate. Bio-Medicine ran a press release from the journal that published the finding, Stem Cells and Development. Unfortunately, that release lacks sufficient detail to know exactly what they did and its full impact. But it is nice to know that someone is developing some options of ways to begin to address this potential roadblock.

Multiple sclerosis just got easier to study. While we often talk about the power of iPS type stem cells to model disease, we probably devote too few electrons to the fact that the process is not easy and often takes a very long time. Taking a skin sample from a patient, reprogramming it to be an iPS cell, and then maturing those into the adult tissue that can mimic the disease in a dish takes months. It varies a bit depending on the type of adult tissue you want, but the nerve tissue that can mimic multiple sclerosis (MS) takes more than six months to create. So a team at the New York Stem Cell Foundation has been working on ways to speed up that process for MS. They now report that they have cut the time in half. This should make it much easier for more teams to jump into the effort of looking for cures for the disease. ScienceCodex ran the foundations press release.

What was Old is New Again: Scientists Transplant Brain Cells into Aged Mice and Reverse Memory Loss

Alzheimer’s disease starts with small, almost imperceptible steps. And then it builds. Sometimes slowly over a period of decades, other times more quickly—in just a matter of years. But no matter the speed of progression, the end outcome is always the same.

Transplanted cells (shown in green) in the hippocampus, 3 months after transplantation.  Cell nuclei are labeled in blue.  [Credit: Leslie Tong and Yadong Huang/Gladstone Institutes]

Transplanted cells (shown in green) in the hippocampus, 3 months after transplantation. Cell nuclei are labeled in blue. [Credit: Leslie Tong and Yadong Huang/Gladstone Institutes]

The sixth leading cause of death in the United State, Alzheimer’s develops as brain cells, or neurons, are destroyed over time. The hippocampus, the brain’s memory center, is the hardest hit, which is why memory loss is the single most common—and most devastating—symptom of the disease.

As a result, scientists have looked to the field of regenerative medicine to replace the vital cells lost to Alzheimer’s. And now, researchers at the Gladstone Institutes in San Francisco have made an important step towards that goal.

Reporting in the latest issue of the Journal of Neuroscience, researchers in the laboratory of Dr. Yadong Huang have successful transplanted early-stage brain cells, called “neuron progenitor cells,” into aged mice that have been modified to mimic Alzheimer’s symptoms. And after doing so, what they saw was extraordinary.

Not only did the cells survive the transplantation—a feat in and of itself—they began to grow and integrate into the molecular circuitry of the brain. And that’s when they noticed changes to the animals’ behavior.

These mice, whose age corresponded to humans in late-stage adulthood, were living with physical signs of memory loss. But after the cell transplants, the team saw signs that memory and learning were restored.

Leslie Tong, a graduate student at Gladstone and the University of California, San Francisco and the paper’s first author, elaborated on the importance of these findings in a news release:

“Working with older animals can be challenging from a technical standpoint, and it was amazing that the cells not only survived but affected activity and behavior.”

For a brain to function normally, there should be a balance between two types of neurons: ‘excitatory’ neurons, that act as the brain’s gas pedal, and ‘inhibitory’ neurons that serve as the brake. If this balance between these two cell types gets thrown out of whack, normal function is disrupted—and cells, especially the inhibitory neurons, degrade and die. Combined with other factors, such as genetic risk and the buildup of toxic proteins—this imbalance plays a key role in the dysfunction that eventually leads to Alzheimer’s.

The success of this treatment not only reveals the importance of maintaining this balance in memory and learning, but is also proof of concept that if neurons are lost—they can in principle be replaced.

Huang is particularly excited about the therapeutic potential of these findings. As he stated in the same news release:

“The fact that we see a functional integration of these cells into the hippocampal circuitry and a…rescue of learning and memory deficits in an aged model of Alzheimer’s disease is very exciting.”

This study, which was supported in part by CIRM, points towards several possible therapeutic strategies that could one day help human brains ravaged by Alzheimer’s regrow the cells they’ve lost—and repair the damage to learning and memory that today remains irreparable. According to Huang:

“This study tells us that if there is any way we can enhance inhibitory neuron function in the hippocampus, like through the development of small molecule compounds, it may be beneficial for Alzheimer’s disease patients.”

The Man Behind the Curtain: Protein Helps Keep Cancer Cells Alive and Kicking

Being diagnosed with brain cancer comes with a sobering sentence: even with the most aggressive treatments, life expectancy for the most common form of brain cancer—called glioblastoma—is less than two years.

One of the key culprits, many scientists now believe, are cancer stem cells. Cancer stem cells are a subset of cancer cells that have three very unique properties: they can self-renew, they can propagate (or multiply) the cancer, and they can transform into the many types of cells that are found in a tumor.

shutterstock_118491940

Cancer stem cells are a relatively new concept, but they have generated a lot of excitement among cancer researchers because they could lead to the design of more effective therapies. And while whether or not they even existed has long been a source of debate among experts, a series of recent research findings have bolstered the notion not only that they exist, but also that they play a significant role in the recurrence of some forms of cancer—including glioblastoma.

Researchers have been identifying, step by step, the many proteins and chemical pathways that form the path from cancer stem cell to tumor. Previous research had found the CDK class of proteins to be present in large quantities in mature cancer cells in patients suffering from glioblastoma. But they suspected something else was at play, helping to keep the CDK proteins switched on in mature cancer cells.

So scientists at McGill University in Canada, led by neurologist Dr. Anita Bellail, dug deeper. In their report, published this week in the journal Nature Communications, the team has pinpointed a new class of proteins at play behind the scenes called SUMO.

Specifically, Bellail and her team observed that the SUMO1 protein in particular modifies a CDK protein called CDK6 in a process the team has dubbed ‘sumylation.’ As Bellail explained in this week’s news release:

“CDK6 sumylation inhibits its degradation and thus stabilizes the CDK6 protein in the cancer.”

In other words, the CDK6 protein does not by itself maintain a presence in the cancer cells. Instead, it requires a little help from SUMO1. As Bellail continued:

“We found that CDK6 sumylation is required for the renewal and growth of the cancer stem cells in glioblastoma.”

It stands to reason, therefore, that shutting off SUMO1 could do the reverse—thus destabilizing CDK6 and, potentially, block the progression of the cancer.

And in further experiments by Bellail and her team, they found exactly that.

These results hold significant promise for finding new ways to treat glioblastoma because now the team has a target: SUMO1. In fact, the research team is now screening for drugs that can target SUMO1 and block it, thus reducing CDK6 levels and, as a result, cancer cells—and one day offering a more optimistic outcome for those diagnosed with glioblastoma.

Want to learn more about cancer stem cells? Check out our 2009 “Spotlight on Cancer Stem Cells” video starring Dr. Michael Clarke, associate director of the Stanford Institute for Stem Cell and Regenerative Medicine.

Stem Cell Stories that Caught our Eye: Multiple Sclerosis, Diabetes, Cornea Repair and of Course, New Stem Cells too Good to be True

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.

Buddy system gets stem cells to stick around. The type of stem cell most likely to be used in a clinical trial today is the mesenchymal stem cell (MSC) found in fat and bone marrow. It is also the type of stem cell most likely to produce vaguely positive or downright disappointing results. In most situations they die within a few days of being transplanted, so the only impact they can have is from the various protein signals they secrete that may trigger the body’s own natural healing processes. They never live up to their stem cell potential to form new adult tissue. A team at Harvard looked at their natural environment and found they most often live near a second type of cell called an endothelial colony-forming cell. When the team transplanted the two cells together they found the MSCs survived for weeks and matured into appropriate adult tissue. Genetic Engineering & Biotechnology News had a nice interview with members of the team about their work that appeared this week in the Proceedings of the National Academy of Sciences.

Fat cells (yellow) descended from transplanted stem cells (green) inside a mouse 28 days after co-transplantation with “buddy cells”  [Courtesy Children’s Hospital]

Fat cells (yellow) descended from transplanted stem cells (green) inside a mouse 28 days after co-transplantation with “buddy cells”
[Courtesy Children’s Hospital]


Master switch for creating brain insulation.
Researchers know how to take a skin cell from a patient, turn it into an iPS type stem cell and then turn those cells into the type of intermediate cell that can become the myelin that insulates our nerves and is lost in Multiple Sclerosis. The problem: the process takes way too long to be a feasible therapy. To get enough of these middleman cells called oligodendrocyte progenitors for a therapy can take as much as a year. Neural stem cells naturally mature into multiple intermediate cells, but prefer to become the progenitors for neurons, which would not help an MS patient. A team at the University of Buffalo looked to see what genetic switches were active in neuron progenitors versus those for myelin. They found that just one of these switches could push the early nerve stem cells to the myelin middlemen. That genetic factor, SOX10, instantly becomes a candidate for a path to a more efficient therapy. Again, Genetic Engineering & Biotechnology News did the best of several write-ups of this work that was published in the Proceedings of the National Academy of Sciences.

You can read about CIRM’s projects working on a cure for MS on our Multiple Sclerosis Fact Sheet.

Can gut be taught to make insulin. Earlier work at Columbia University had shown that in mice you can turn off a single gene and get normal gut cells to secrete insulin and to do so in response to sugar in the bloodstream. Now the team has made the often difficult transition of moving from mouse results to humans, or in this case human gut cells in a dish. They matured human stem cells into gut tissue and then shut down the one gene. The resulting cells produced insulin in response to sugar in their environment. The research published in Nature Communication got coverage on a few sites including HealthDay.

Early success in cornea repair poised to get even better. One of the stem cell field’s early successes has been work pioneered in Italy using a type of stem cell found in the cornea of the eye. When a patient has the cornea of one eye damaged they harvest these cells, called limbal stem cells, from the healthy eye and transplant them to the damaged eye. It often works quite well, but not always and the success has been correlated with how many actual limbal stem cells are among the cells transplanted. It has been difficult to sort out and purify the stem cells until now. A team from three Harvard affiliated hospitals has found a marker that let them transplant purer human limbal stem cells into mice and they saw consistent regrowth of damaged corneas. RedOrbit wrote up the research that was published in Nature.

STAP stem cell retraction everywhere. When Japanese and American researchers published a new, simple method for creating stem cells in January it got way more news coverage than an unconfirmed and unconventional piece of research should have. Most of that coverage failed to include the caveat that the work needed to be replicated to confirm the findings. In less than six months, the research community quickly reported repeated failures to replicate the work and more recently found outright errors in the published papers. When the journal that published the work, Nature, formally retracted the papers this week it was good to see that this “oops-ignore-our-first-article” seemed to get equal play. To show the reach of this news, I have included the Associated Press version from the tiny Logansport Pharos Tribune, which averages about 12 pages a day and is the closest real newspaper to the tiny Indiana town where I grew up.

Don Gibbons