National honor for helping “the blind see”

Those of us fortunate to have good health take so many things for granted, not the least of which is our ability to see. But, according to the World Health Organization, there are 39 million people worldwide who are blind, and another 246 million who are visually impaired. Any therapy, any device, that can help change that is truly worthy of celebration.

Dr.MarkHumayun2 copy

Dr. Mark Humayun: Photo courtesy USC

That’s why we are celebrating the news that Professor Mark Humayun has been awarded the National Medal of Technology and Innovation, the nation’s top technology honor, by President Obama.

Humayun, a researcher at USC’s Keck School of Medicine and a CIRM grantee, is being honored for his work in developing an artificial retina, one that enables people with a relatively rare kind of blindness to see again.

But we are also celebrating the potential of his work that we are funding that could help restore sight to millions of people suffering from the leading cause of blindness among the elderly. But we’ll get back to that in a minute.

First, let’s talk about the invention that has earned him this prestigious award. It’s called the Argus II and it can help people with retinitis pigmentosa, an inherited degenerative disease that slowly destroys a person’s vision. It affects around 100,000 Americans.

The Argus II uses a camera mounted on glasses that send signals to an electronic receiver that has been implanted inside the eye. The receiver then relays those signals through the optic nerve to the brain where they are interpreted as a visual image.

In a story posted on the USC website, USC President C. L. Max Nikias praised Humayun’s work:

“He dreamed the impossible: to help the blind see. With fearless imagination, bold leadership and biomedical expertise, he and his team made that dream come true with the world’s first artificial retina. USC is tremendously proud to be Professor Humayun’s academic home.”

At CIRM we are tremendously proud to be funding the clinical trial that Humayun and his team are running to find a stem cell therapy for age-related macular degeneration (AMD), the leading cause of vision loss in the world.  It’s estimated that by 2020 more than 6 million Americans will suffer from AMD.

Humayun’s team is using embryonic stem cells to produce the support cells, or RPE cells, needed to replace those lost in AMD. We recently produced this video that highlights this work, and other CIRM-funded work that targets vision loss.

In a statement released by the White House honoring all the winners, President Obama said:

“Science and technology are fundamental to solving some of our nation’s biggest challenges. The knowledge produced by these Americans today will carry our country’s legacy of innovation forward and continue to help countless others around the world. Their work is a testament to American ingenuity.”

Which is why we are honored to be partners with Humayun and his team in advancing this research and, hopefully, helping find a treatment for millions of people who dream of one day being able to see again.

 

 

 

 

A Win for Diabetes: Scientists Make Functional Pancreatic Cells From Skin

Today is an exciting day for diabetes research and patients. For the first time, scientists have succeeded in making functional pancreatic beta cells from human skin. This new method for making the insulin-producing cells of the pancreas could produce a new, more effective treatment for patients suffering from diabetes.

Researchers at the Gladstone Institutes and the University of California, San Francisco published these promising findings today in the journal Nature Communications.

Making pancreatic cells from skin

They used a technique called direct reprogramming to turn human skin cells directly into pancreatic beta cells without having to go all the way back to a pluripotent stem cell state. The skin cells were treated with factors used to generate induced pluripotent stem cells (iPSCs) and with pancreatic-specific molecules. This cocktail of factors and molecules shut off the skin genes and turned on genes of the pancreas.

The end product was endoderm progenitor cells, which are like stem cells but can only generate cell types specific to organs derived from the endoderm layer (for example: lungs, thyroid, pancreas). The scientists took these endoderm progenitors and further coaxed them into mature, pancreatic beta cells after treatment with another cocktail of molecules.

Functioning human pancreatic cells after they’ve been transplanted into a mouse. (Image: Saiyong Zhu, Gladstone)

Functioning human pancreatic cells after they’ve been transplanted into a mouse. (Image: Saiyong Zhu, Gladstone)

While the pancreatic cells they made looked and acted like the real thing in a dish (they were able to secrete insulin when exposed to glucose), the authors needed to confirm that they functioned properly in animals. They transplanted the mature beta cells into mice that were engineered to have diabetes, and observed that the human beta cells protected the mice from becoming diabetic by properly regulating their blood glucose levels.

Importantly, none of the mice receiving human cells got tumors, which is always a concern when transplanting reprogrammed cells or cells derived from pluripotent stem cells.

What does this mean?

This study is groundbreaking because it offers a new and more efficient method to make functioning human beta cells in mass quantities.

Dr. Sheng Ding, a CIRM funded senior investigator at the Gladstone and co-senior author, explained in a Gladstone news release:

Sheng Ding

Sheng Ding

“This new cellular reprogramming and expansion paradigm is more sustainable and scalable than previous methods. Using this approach, cell production can be massively increased while maintaining quality control at multiple steps. This development ensures much greater regulation in the manufacturing process of new cells. Now we can generate virtually unlimited numbers of patient-matched insulin-producing pancreatic cells.”

 

Matthias Hebrok, director of the Diabetes Center at UCSF and co-senior author on paper discussed the potential research and clinical applications of their findings:

Mattias Hebrok

Matthias Hebrok

“Our results demonstrate for the first time that human adult skin cells can be used to efficiently and rapidly generate functional pancreatic cells that behave similar to human beta cells. This finding opens up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimization of cell therapy approaches.”

 

The study does mention the caveat that their direct reprogramming approach wasn’t able to generate all the cell types of the pancreas. Having these support cells would better recreate the pancreatic environment and likely improve the function of the transplanted beta cells.

Lastly, I find this study exciting because it kills two birds with one stone. Scientists can use this technique to make better cellular models of diabetes to understand why the disease happens, and they could also develop new cell replacement therapies in humans. Already, stem cell derived pancreatic beta cells are being tested in human clinical trials for type 1 diabetes (one of them is a CIRM-funded clinical trial by Viacyte) and it seems likely that beta cells derived from skin will follow suit.


Related links:

New type of diabetes caused by old age may be treatable

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:

The best scientists always want to know more

Sir Isaac Newton

Sir Isaac Newton

Some years ago I was in the Wren Library at Trinity College, Cambridge in England when I noticed a display case with a cloth over it. Being a naturally curious person, downright nosy in fact, I lifted the cloth. In the display case was a first edition of Sir Isaac Newton’s Principia Mathematica and in the margins were notes, corrections put there by Newton for the second edition.

It highlighted for me how the best scientists never stop working, never stop learning, never stop trying to improve what they do.

That came back to me when I saw a news release from ViaCyte, a company we are funding in a Phase 1 clinical trial to treat type 1 diabetes.  The news release announced results of a study showing that insulin-producing cells, created in the lab from embryonic stem cells, can not only mature but also function properly after being implanted in a capsule-like device and placed under the skin of an animal model.

VC-01-cross-section-5

Now the clinical trial we are funding with ViaCyte uses a similar, but slightly different set of cells in people. The device in the trial contains what ViaCyte calls PEC-01™ pancreatic progenitor cells. These are essentially an earlier stage of the mature pancreatic cells that our body uses to produce insulin. The hope is that when implanted in the body, the cells will mature and then behave like adult pancreatic cells, secreting insulin and other hormones to keep blood glucose levels stable and healthy.

Those cells and that device are being tested in people with type 1 diabetes right now.

Learning more

But in this study ViaCyte wanted to know if beta cells, a more mature version of the cells they are using in our trial, would also work or have any advantages over their current approach.

The good news, published in the journal Stem Cells Translational Medicine,  is that these cells did work. As they say in their news release:

“The animal study also demonstrated for the first time that when encapsulated in a device and implanted into mice, these more mature cells are capable of producing functional pancreatic beta cells. ViaCyte is also the first to show that these further differentiated cells can function in vivo following cryopreservation, a valuable process step when contemplating clinical and commercial application.”

This does not mean ViaCyte wants to change the cells it uses in the clinical trial. As President and CEO Paul Laikind, PhD, makes clear:

“For a number of reasons we believe that the pancreatic progenitor cells that are the active component of the VC01 product candidate are better suited for cell replacement therapy. However, the current work has expanded our fundamental knowledge of beta cell maturation and could lead to further advances for the field.”

And that’s what I mean about the best scientists are the ones who keeping searching, keeping looking for answers. It may not help them today, but who knows how important that work will prove in the future.

Two for 2.0 and Two for us

It began as an ambitious idea; yesterday it became a reality when the CIRM Board approved two projects under CIRM 2.0, one of them a Phase 3 clinical trial for a deadly form of skin cancer.

Just to recap, CIRM 2.0 was introduced by Dr. C. Randal Mills when he took over as President and CEO of the stem cell agency last year. The idea is to speed up the way we work, to get money to the most promising therapies and the best science as quickly as possible. It puts added emphasis on speed, patients and partnerships.

Yesterday our Board approved the first two projects to come before them under this new way of working. One was for almost $18 million for NeoStem, which is planning a Phase 3 clinical trial for metastatic melanoma, a disease that last year alone claimed more than 10,000 lives in the U.S.

This will be the first Phase 3 trial we have funded so clearly it’s quite a milestone for us and for NeoStem. If it proves effective in this trial it could well be approved by the Food and Drug Administration (FDA) for use in melanoma patients. The therapy itself is unique in that it uses the patient’s own tumor cells to create a personalized therapy, one that is designed to engage the patient’s immune system and destroy the cancer.

The Board also approved almost $5 million for Cedars-Sinai in Los Angeles to do the late-stage research needed to apply to the FDA for approval for a clinical trial to treat retinitis pigmentosa (RP). RP is a nasty, degenerative condition that slowly destroys a patient’s vision. There is no cure and no effective therapy.

We are currently funding another clinical trial in this area. The two projects use different types of cells and propose different methods of reducing RP’s devastation. CIRM has a record of trying multiple routes to achieve success when dealing with unmet medical needs.

As Dr. Mills said in a news release, both the therapies approved for funding yesterday support our mission:

“CIRM 2.0 is designed to accelerate the development of treatments for people with unmet medical needs, and these two projects clearly fit that description. With the Board’s approval today we will now get this work up and running within the next 45 days. But that’s just the start. We are not just providing financial support, we are also partnering with these groups to provide expertise, guidance and other kinds of support that these teams need to help them be successful. That’s the promise of CIRM 2.0. Faster funding, better programs and a more comprehensive approach to supporting their progress.”

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

Two seemed to be the number of the day yesterday with the Board welcoming two new members.

Dr. Adriana Padilla is the new Patient Advocate Board member for type 2 Diabetes. She’s a family physician, a member of the University of California, San Francisco-Fresno medical faculty, and an award-winning researcher with expertise in diabetes and its impact on Latino families and the health system in California’s Central Valley. She is also active in the National Hispanic Medical Association (NHMA) and is also a member of the American Diabetes Association.

Dr. Padilla said she hopes her presence will help increase awareness among Latinos of the importance of the work the agency is doing:

“When I was asked about being on the Board I did some research to find out more and it was really touching to learn about some of the exciting work that has been done by the agency and the possibilities that can be done for patients, including those I serve, members of the Latino community.”

Dr. Bob Price is the Associate Vice Chancellor for Research and a Professor of Political Science at U.C. Berkeley. His academic and teaching interests include comparative politics, with a particular interest in the politics of South Africa. This is Dr. Price’s second time on the Board.  He previously served as the alternate to UC Berkeley Chancellor Robert Birgeneau.

Although he has only been off the Board for a little more than a year Dr. Price said he is aware of the big changes that have taken place in that time and is looking forward to being a part of the new CIRM 2.0.

Stem cell stories that caught our eye: new ways to reprogram, shifting attitudes on tissue donation, and hockey legend’s miracle questioned

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.

Insulin-producing cells produced from skin. Starting with human skin cells a team at the University of Iowa has created iPS-type stem cells through genetic reprogramming and matured those stem cells into insulin-producing cells that successfully brought blood-sugar levels closer to normal when transplanted in mice.

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left). [Credit: University of Iowa]

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left).
[Credit: University of Iowa]

The cells did not completely restore blood-sugar levels to normal, but did point to the possibility of achieving that goal in the future, something the team leader Nicholas Zavazava noted in an article in the Des Moines Register, calling the work an “encouraging first step” toward a potential cure for diabetes.

The Register discussed the possibility of making personalized cells that match the genetics of the patient and avoiding the need for immune suppression. This has long been a goal with iPS cells, but increasingly the research community has turned to looking for options that would avoid immune rejection with donor cells that could be off-the-shelf and less expensive than making new cells for each patient.

Heart cells from reprogramming work in mice. Like several other teams, a group in Japan created beating heart cells from iPS-type stem cells. But they went the additional step of growing them into sheets of heart muscle that when transplanted into mice integrated into the animals own heart and beat to the same rhythm.

The team published the work in Cell Transplantation and the news agency AlianzaNews ran a story noting that it has previously been unclear if these cells would get in sync with the host heart muscle. The result provides hope this could be a route to repair hearts damaged by heart attack.

Patient attitudes on donating tissue. A University of Michigan study suggests most folks don’t care how you use body tissue they donate for research if you ask them about research generically. But their attitudes change when you ask about specific research, with positive responses increasing for only one type of research: stem cell research.

On the generic question, 69 percent said go for it, but when you mentioned the possibility of abortion research more than half said no and if told the cells might lead to commercial products 45 percent said nix. The team published their work in the Journal of the American Medical Association and HealthCanal picked up the university’s press release that quoted the lead researcher, Tom Tomlinson, on why paying attention to donor preference is so critical:

“Biobanks are becoming more and more important to health research, so it’s important to understand these concerns and how transparent these facilities need to be in the research they support.”

CIRM has begun building a bank of iPS-type stem cells made from tissue donated by people with one of 11 diseases. We went through a very detailed process to develop uniform informed consent forms to make sure the donors for our cell bank knew exactly how their cells could be used. Read more about the consent process here.

Mainstream media start to question hockey legend’s miracle. Finally some healthy skepticism has arrived. Hockey legend Gordie Howe’s recovery from a pair of strokes just before the holidays was treated by the general media as a true Christmas miracle. The scientific press tried to layer the coverage with some questions of what we don’t know about his case but not the mainstream media. The one exception I saw was Brad Fikes in the San Diego Union Tribune who had to rely on a couple of scientists who were openly speaking out at the time. We wrote about their concerns then as well.

Now two major outlets have raised questions in long pieces back-to-back yesterday and this morning. The Star in hockey-crazed Canada wrote the first piece and New York Magazine wrote today’s. Both raise serious questions about whether stem cells could have been the cause of Howe’s recovery and are valuable additions to the coverage.

10 Years/10 Therapies: 10 Years after its Founding CIRM will have 10 Therapies Approved for Clinical Trials

In 2004, when 59 percent of California voters approved the creation of CIRM, our state embarked on an unprecedented experiment: providing concentrated funding to a new, promising area of research. The goal: accelerate the process of getting therapies to patients, especially those with unmet medical needs.

Having 10 potential treatments expected to be approved for clinical trials by the end of this year is no small feat. Indeed, it is viewed by many in the industry as a clear acceleration of the normal pace of discovery. Here are our first 10 treatments to be approved for testing in patients.

HIV/AIDS. The company Calimmune is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease.

Spinal cord injury patient advocate Katie Sharify is optimistic about the latest clinical trial led by Asterias Biotherapeutics.

Spinal cord injury patient advocate Katie Sharify is optimistic about the clinical trial led by Asterias Biotherapeutics.

Spinal Cord Injury. The company Asterias Biotherapeutics uses cells derived from embryonic stem cells to heal the spinal cord at the site of injury. They mature the stem cells into cells called oligodendrocyte precursor cells that are injected at the site of injury where it is hoped they can repair the insulating layer, called myelin, that normally protects the nerves in the spinal cord.

Heart Disease. The company Capricor is using donor cells derived from heart stem cells to treat patients developing heart failure after a heart attack. In early studies the cells appear to reduce scar tissue, promote blood vessel growth and improve heart function.

Solid Tumors. A team at the University of California, Los Angeles, has developed a drug that seeks out and destroys cancer stem cells, which are considered by many to be the reason cancers resist treatment and recur. It is believed that eliminating the cancer stem cells may lead to long-term cures.

Leukemia. A team at the University of California, San Diego, is using a protein called an antibody to target cancer stem cells. The antibody senses and attaches to a protein on the surface of cancer stem cells. That disables the protein, which slows the growth of the leukemia and makes it more vulnerable to other anti-cancer drugs.

Sickle Cell Anemia. A team at the University of California, Los Angeles, is genetically modifying a patient’s own blood stem cells so they will produce a correct version of hemoglobin, the oxygen carrying protein that is mutated in these patients, which causes an abnormal sickle-like shape to the red blood cells. These misshapen cells lead to dangerous blood clots and debilitating pain The genetically modified stem cells will be given back to the patient to create a new sickle cell-free blood supply.

Solid Tumors. A team at Stanford University is using a molecule known as an antibody to target cancer stem cells. This antibody can recognize a protein the cancer stem cells carry on their cell surface. The cancer cells use that protein to evade the component of our immune system that routinely destroys tumors. By disabling this protein the team hopes to empower the body’s own immune system to attack and destroy the cancer stem cells.

Diabetes. The company Viacyte is growing cells in a permeable pouch that when implanted under the skin can sense blood sugar and produce the levels of insulin needed to eliminate the symptoms of diabetes. They start with embryonic stem cells, mature them part way to becoming pancreas tissues and insert them into the permeable pouch. When transplanted in the patient, the cells fully develop into the cells needed for proper metabolism of sugar and restore it to a healthy level.

HIV/AIDS. A team at The City of Hope is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease

Blindness. A team at the University of Southern California is using cells derived from embryonic stem cell and a scaffold to replace cells damaged in Age-related Macular Degeneration (AMD), the leading cause of blindness in the elderly. The therapy starts with embryonic stem cells that have been matured into a type of cell lost in AMD and places them on a single layer synthetic scaffold. This sheet of cells is inserted surgically into the back of the eye to replace the damaged cells that are needed to maintain healthy photoreceptors in the retina.

Moving one step closer to a therapy for type 1 diabetes

When I was a medical journalist one word I always shied away from was “breakthrough”. There are few true breakthroughs in medicine. Usually any advance is the result of years and years of work. That’s why good science takes time; it takes hundreds of small steps to make a giant leap forward.

Today we took one of those steps. ViaCyte, a company we have supported for many years, just announced that the first patient has been successfully implanted with a device designed to help treat type 1 diabetes.

It’s an important milestone for the company, for us, and of course for people with type 1 diabetes. As Dr. Paul Laikind, the President and CEO of ViaCyte, said in a news release, this is an exciting moment:

“To our knowledge, this is the first time that an embryonic stem cell-derived cell replacement therapy for diabetes has been studied in human subjects, and it represents the culmination of a decade of effort by the ViaCyte team, our collaborators, and our supporters at the California Institute for Regenerative Medicine and at JDRF.”

The VC-01 device is being tested in a clinical trial at the University of California, San Diego Health System. There are two goals; first to see if it is safe; and secondly to see if it helps patients who have type 1 diabetes. When the device is implanted under the skin the cells inside are able to sense when blood sugar is high and, in response, secrete insulin to restore it to a healthy level.

The beauty of the VC-01 is that while it lets cells secrete insulin out, it prevents the body’s own immune system from getting in and attacking the cells.

The device is about the length and thickness of a credit card but only half as wide which makes it easy to implant under the skin.

Today’s news, that this is now truly out of the lab and being tested in patients is an important step in a long road to showing that it works in patients. The people at ViaCyte, who have been working hard on this project for many years, know that they still have a long way to go but for today at least, this step probably feels a little bit more like a skip for joy.

Scientists Reach Yet Another Milestone towards Treating Type 1 Diabetes

There was a time when having type 1 diabetes was equivalent to a death sentence. Now, thanks to advances in science and medicine, the disease has shifted from deadly to chronic.

But this shift, doctors argue, is not good enough. The disease still poses significant health risks, such as blindness and loss of limbs, as the patients get older. There has been a renewed effort, therefore, to develop superior therapies—and those based on stem cell technology have shown significant promise.

Human stem cell-derived beta cells that have formed islet like clusters in a mouse. Cells were transplanted to the kidney capsule and photo was taken two weeks later by which time the beta cells are making insulin and have cured the mouse's diabetes. [Credit: Douglas Melton]

Human stem cell-derived beta cells that have formed islet like clusters in a mouse. Cells were transplanted to the kidney capsule and photo was taken two weeks later by which time the beta cells are making insulin and have cured the mouse’s diabetes. [Credit: Douglas Melton]

Indeed, CIRM-funded scientists at San Diego-based Viacyte, Inc. recently received FDA clearance to begin clinical trials of their VC-01 product candidate that delivers insulin via healthy beta cells contained in a permeable, credit card-sized pouch.

And now, scientists at Harvard University have announced a technique for producing mass quantities of mature beta cells from embryonic stem cells in the lab. The findings, published today in the journal Cell, offer additional hope for the millions of patients and their families looking for a better way to treat their condition.

The team’s ability to generate billions of healthy beta cells—cells within the pancreas that produce insulin in order to maintain normal glucose levels—has a particular significance to the study’s senior author and co-scientific director of the Harvard Stem Cell Institute, Dr. Doug Melton. 23 years ago, his infant son Sam was diagnosed with type 1 diabetes and since that time Melton has dedicated his career to finding better therapies for his son and the millions like him. Melton’s daughter, Emma, has also been diagnosed with the disease.

Type 1 diabetes is an autoimmune disorder in which the body’s immune system systematically targets and destroys the pancreas’ insulin-producing beta cells.

In this study, the team took human embryonic stem cells and transformed them into healthy beta cells. They then transplanted them into mice that had been modified to mimic the signs of diabetes. After closely monitoring the mice for several weeks, they found that their diabetes was essentially ‘cured.’ Said Melton:

“You never know for sure that something like this is going to work until you’ve tested it numerous ways. We’ve given these cells three separate challenges with glucose in mice and they’ve responded appropriately; that was really exciting.”

The researchers are undergoing additional pre-clinical studies in animal models, including non-human primates, with the hopes that the 150 million cells required for transplantation are also protected from the body’s immune system, and not destroyed.

Melton’s team is collaborating with Medical Engineer Dr. Daniel G. Anderson at MIT to develop a protective implantation device for transplantation. Said Anderson of Melton’s work:

“There is no question that the ability to generate glucose-responsive, human beta cells through controlled differentiation of stem cells will accelerate the development of new therapeutics. In particular, this advance opens the doors to an essentially limitless supply of tissue for diabetic patients awaiting cell therapy.”

Stories of Hope: Diabetes

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.

The last thing Maria Torres expected was to be diagnosed with type 2 diabetes. She exercised, ate well and kept her weight under control. There had to be some mistake. Maria asked her doctor to repeat the tests, but the results were the same. At 43, for reasons no one could fully explain, she had diabetes, and her life was going to change dramatically.

Maria Torres' diabetes diagnoses was frightening—but she is hopeful that stem cell therapies could one day change how doctors treat this devastating condition.

Maria Torres’ diabetes diagnoses was frightening—but she is hopeful that stem cell therapies could one day change how doctors treat this devastating condition.

“It really scared me,” says Maria. “I thought I was going to die soon.”

That Maria doubted her diagnosis is no surprise. Type 2 diabetes is often associated with obesity, and she didn’t fit the profile. Most likely, some undiscovered genetic component had made her susceptible to the disease.

Regardless, she now had to rework her life to manage the diabetes. Her cells had developed a condition called insulin resistance. Though her pancreas was producing insulin, which tells cells to take in blood sugar, the cells were not cooperating. As a result, glucose was accumulating in her blood, putting her at risk for heart disease, nerve damage, eye issues and a host of other problems.

To help her cells absorb glucose, she needs regular insulin injections. Maria injects the hormone five times a day and must often measure her blood sugar levels even more frequently.

Faithfully following this regimen has kept her alive for 20 years, but insulin is not a cure. Even with the regular injections, she faces dramatic mood swings and more serious complications as glucose levels rise and fall.

Working for a Cure
One of the most promising strategies to cure diabetes is to transplant beta cells, which sense blood sugar levels and produce insulin to reduce them. Patients with type 1 diabetes would benefit because new beta cells would replace the ones they’d lost to disease. Type 2 patients, like Maria, could increase their body’s ability to produce insulin, lowering blood sugar levels and alleviating the need for injections.

With almost $40 million in funding from CIRM, a San Diego-based company named ViaCyte is working on this solution. They have spent years developing new methods to turn human embryonic stem cells into insulin-producing beta cells. It hasn’t been easy. Stem cells are promising because they can form any tissue. However, to make a specific type of cell, researchers must replicate the exact signals that transform a stem cell into a beta cell, rather than a neuron or muscle cell.

In 2008, the company succeeded, but with a clever twist. They created progenitor cells, one step shy of mature beta cells, and allowed them to finish developing in the body. In animal studies, the hardier progenitor cells survived the transplant process and, once mature, began producing insulin. The project has another innovation up its sleeve: these progenitor cells are first placed in a porous capsule, about the size of a credit card, before transplantation under the skin. This device allows transfer of blood sugar, insulin, oxygen, and other molecules but keeps cells out, thus avoiding the possible attack and rejection by the patient’s own immune system.

ViaCyte’s goal is to start clinical trials for type 1 diabetes by the end of 2014. But the company eventually hopes to also help those with type 2. Maria Torres is eager for them to succeed, both for herself and her family.

“I have three kids, and I know they could have the same thing I have,” says Maria. “If they find a cure, for me, that’s peace of mind.”

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