‘Ask The Expert’ on Facebook Live about the power of stem cells to reverse damage caused by a stroke.

facebook-live-brand-awarenessIt’s not often you get a chance to ask a world class stem cell expert a question about their work, and how it might help you or someone you love. But on Thursday, May 31 you can do just that.

CIRM is hosting a special ‘Ask the Expert’ event on Facebook Live. The topic is Strokes and Stem Cells. Just head over to our Facebook Page on May 31st from noon till 1pm PST to experience it live. You can also re-watch the event any time after the broadcast has ended from our Facebook videos page.

Steinberg

We will be joined by Dr. Gary Steinberg, chair of neurosurgery at Stanford University, who will talk to us about his work in helping reverse the damage caused by a stroke, even for people who experienced a brain attack several years ago.

CIRM Senior Science Officer, Dr. Lila Collins, will talk about other stem cell research targeting stroke, its promise and some of the problems that still need to be overcome.

You will have a chance to ask questions of both our experts, either live on the day or by sending us questions in advance at info@cirm.ca.gov.

We’ll post reminders on Facebook so make sure to follow us. But for now, mark the date and time on your diary and please feel free to share this information with anyone you think might be interested.

It promises to be a fascinating event.

 

 

Stem Cell Agency Heads to Inland Empire for Free Patient Advocate Event

UCRiversidePatientAdvocateMtg_EventBrite copy

I am embarrassed to admit that I have never been to the Inland Empire in California, the area that extends from San Bernardino to Riverside counties.  That’s about to change. On Monday, April 16th CIRM is taking a road trip to UC Riverside, and we’re inviting you to join us.

We are holding a special, free, public event at UC Riverside to talk about the work that CIRM does and to highlight the progress being made in stem cell research. We have funded 45 clinical trials in a wide range of conditions from stroke and cancer, leukemia, lymphoma, vision loss, diabetes and sickle cell disease to name just a few. And will talk about how we plan on funding many more clinical trials in the years to come.

We’ll be joined by colleagues from both UC Riverside, and City of Hope, talking about the research they are doing from developing new imaging techniques to see what is happening inside the brain with diseases like Alzheimer’s, to using a patient’s own cells and immune system to attack deadly brain cancers.

It promises to be a fascinating event and of course we want to hear from you, our supporters, friends and patient advocates. We are leaving plenty of time for questions, so we can hear what’s on your mind.

So, join us at UC Riverside on Monday, April 16th from 12.30pm to 2pm. The doors open at 11am so you can enjoy a poster session (highlighting some of the research at UCR) and a light lunch before the event. Parking will be available on site.

Visit the Eventbrite page we have created for all the information you’ll need about the event, including a chance to RSVP and book your place.

The event is free so feel free to share this with anyone and everyone you think might be interested in joining us.

 

 

Stem Cell Stories That Caught our Eye: Stem Cell Therapies for Stroke and Duchenne Muscular Dystrophy Patients

With the Thanksgiving holiday behind us, we’re back to the grind at CIRM. Here are two exciting CIRM-funded stem cell stories that happened while you were away.

Stanford Scientists Are Treating Stroke Patients with Stem Cells

Smithsonian Magazine featured the work of a CIRM-funded scientist in their December Magazine issue. The article, “A Neurosurgeon’s Remarkable Plan to Treat Stroke Victims with Stem Cells”, features Dr. Gary Steinberg, who is the Chair of Neurosurgery at Stanford Medical Center and the founder of the Stanford Stroke Center.

Gary Steinberg (Photo by Jonathan Sprague)

The brain and its 100 billion cells need blood, which carries oxygen and nutrients, to function. When that blood supply is cut off, brain cells start to die and patients experience a stroke. Stroke can happen in one of two ways: either by blood clots that block the arteries and blood vessels that send blood to the brain or by blood vessels that burst within the brain itself. Symptoms experienced by stroke victims vary based on the severity of the stroke, but often patients report experiencing numbness or paralysis in their limbs or face, difficulty walking, talking and understanding.

Steinberg and his team at Stanford are developing a stem cell treatment to help stroke patients. Steinberg believes that not all brain cells die during a stroke, but rather some brain cells become “dormant” and stop functioning instead. By transplanting stem cells derived from donated bone marrow into the brains of stroke patients, Steinberg thinks he can wake up these dormant cells much like how the prince wakens Sleeping Beauty from her century of enchanted sleep.

Basically, the transplanted cells act like a defibrillator for the dormant cells in the stroke-damaged area of the brain. Steinberg thinks that the transplanted cells secrete proteins that signal dormant brain cells to wake up and start functioning normally again, and that they also trigger a “helpful immune response” that prompts the brain to repair itself.

Sonia has seen first hand how a stroke can rob you of even your most basic abilities.

Steinberg tested this stem cell treatment in a small clinical trial back in 2013. 18 patients were treated and many of them showed improvements in their symptoms. The Smithsonian piece mentions a particular patient who had a remarkable response to the treatment. Sonia Olea Coontz, at age 32, suffered a stroke that robbed her of most of her speech and her ability to use her right arm and leg. After receiving Steinberg’s stem cell treatment, Sonia rapidly improved and was able to raise her arm above her head and gained most of her speech back. You can read more about her experience in our Stories of Hope.

In collaboration with a company called SanBio, Steinberg’s team is now testing this stem cell therapy in 156 stroke patients in a CIRM-funded phase 2 clinical trial. The trial will help answer the question of whether this treatment is safe and also effective in a larger group of patients.

The Smithsonian article, which I highly recommend reading, shared Steinberg’s future aspirations to pursue stem cell therapies for traumatic brain and spinal cord injuries as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS.

 

Capricor Approved to Launch New Clinical Trial for Duchenne Muscular Dystrophy

On Wednesday, Capricor Therapeutics achieved an exciting milestone for its leading candidate CAP-1002 – a stem cell-based therapy developed to treat boys and young men with a muscle-wasting disease called Duchenne muscular dystrophy (DMD).

The Los Angeles-based company announced that it received approval from the US Food and Drug Administration (FDA) for their investigational new drug (IND) application to launch a new clinical trial called HOPE II that’s testing repeated doses of CAP-1002 cells in DMD patients. The cells are derived from donated heart tissue and are believed to release regenerative factors that strengthen heart and other muscle function in DMD patients.

Capricor is currently conducting a Phase 2 trial, called HOPE-1, that’s testing a single dose of CAP-1002 cells in 24 DMD patients. CIRM is funding this trial and you can learn more about it on our clinical dashboard website and watch a video interview we did with a young man who participated in the trial.

Earlier this year, the company shared encouraging, positive results from the HOPE-1 trial suggesting that the therapy was improving some heart function and upper limb movement six months after treatment and was well-tolerated in patients. The goal of the new trial will be to determine whether giving patients repeated doses of the cell therapy over time will extend the benefits in upper limb movement in DMD patients.

In a news release, Capricor President and CEO Dr. Linda Marbán shared her company’s excitement for the launch of their new trial and what this treatment could mean for DMD patients,

Linda Marban, CEO of Capricor Therapeutics

“The FDA’s clearance of this IND upon its initial submission is a significant step forward in our development of CAP-1002. While there are many clinical initiatives in Duchenne muscular dystrophy, this is one of the very few to focus on non-ambulant patients. These boys and young men are looking to maintain what function they have in their arms and hands and, based on our previous study, we think CAP-1002 may be able to do exactly that.”

New stem cell technique gives brain support cells a starring role

Gage et al

The Salk team. From left: Krishna Vadodaria, Lynne Moore, Carol Marchetto, Arianna Mei, Fred H. Gage, Callie Fredlender, Ruth Keithley, Ana Diniz Mendes. Photo courtesy Salk Institute

Astrocytes are some of the most common cells in the brain and central nervous system but they often get overlooked because they play a supporting role to the more glamorous neurons (even though they outnumber them around 50 to 1). But a new way of growing those astrocytes outside the brain could help pave the way for improved treatments for stroke, Alzheimer’s and other neurological problems.

Astrocytes – which get their name because of their star shape (Astron – Greek for “star” and “kyttaron” meaning cell) – have a number of key functions in the brain. They provide physical and metabolic support for neurons; they help supply energy and fuel to neurons; and they help with detoxification and injury repair, particularly in terms of reducing inflammation.

Studying these astrocytes in the lab has not been easy, however, because existing methods of producing them have been slow, cumbersome and not altogether effective at replicating their many functions.

Finding a better way

Now a team at the Salk Institute, led by CIRM-funded Professor Fred “Rusty” Gage, has developed a way of using stem cells to create astrocytes that is faster and more effective.

Their work is published in the journal Stem Cell Reports. In a news release, Gage says this is an important discovery:

“This work represents a big leap forward in our ability to model neurological disorders in a dish. Because inflammation is the common denominator in many brain disorders, better understanding astrocytes and their interactions with other cell types in the brain could provide important clues into what goes wrong in disease.”

Stylized microscopy image of an astrocyte (red) and neuron (green). (Salk Institute)

In a step by step process the Salk team used a series of chemicals, called growth factors, to help coax stem cells into becoming, first, generic brain cells, and ultimately astrocytes. These astrocytes not only behaved like the ones in our brain do, but they also have a particularly sensitive response to inflammation. This gives the team a powerful tool in helping develop new treatment to disorders of the brain.

But wait, there’s more!

As if that wasn’t enough, the researchers then used the same technique to create astrocytes from induced pluripotent stem cells (iPSCs) – adult cells, such as skin, that have been re-engineered to have the ability to turn into any other kind of cell in the body. Those man-made astrocytes also showed the same characteristics as natural ones do.

Krishna Vadodaria, one of the lead authors on the paper, says having these iPSC-created astrocytes gives them a completely new tool to help explore brain development and disease, and hopefully develop new treatments for those diseases.

“The exciting thing about using iPSCs is that if we get tissue samples from people with diseases like multiple sclerosis, Alzheimer’s or depression, we will be able to study how their astrocytes behave, and how they interact with neurons.”

Avalanches of exciting new stem cell research at the Keystone Symposia near Lake Tahoe

From January 8th to 13th, nearly 300 scientists and trainees from around the world ascended the mountains near Lake Tahoe to attend the joint Keystone Symposia on Neurogenesis and Stem Cells at the Resort at Squaw Creek. With record-high snowfall in the area (almost five feet!), attendees had to stay inside to stay warm and dry, and even when we lost power on the third day on the mountain there was no shortage of great science to keep us entertained.

Boy did it snow at the Keystone Conference in Tahoe!

Boy did it snow at the Keystone Conference in Tahoe!

One of the great sessions at the meeting was a workshop chaired by CIRM’s Senior Science Officer, Dr. Kent Fitzgerald, called, “Bridging and Understanding of Basic Science to Enable/Predict Clinical Outcome.” This workshop featured updates from the scientists in charge of three labs currently conducting clinical trials funded and supported by CIRM.

Regenerating injured connections in the spinal cord with neural stem cells

Mark Tuszynski, UCSD

Mark Tuszynski, UCSD

The first was a stunning talk by Dr. Mark from UCSD who is investigating how neural stem cells can help outcomes for those with spinal cord injury. The spinal cord contains nerves that connect your brain to the rest of your body so you can sense and move around in your environment, but in cases of severe injury, these connections are cut and the signal is lost. The most severe of these injuries is a complete transection, which is when all connections have been cut at a given spot, meaning no signal can pass through, just like how no cars could get through if a section of the Golden Gate Bridge was missing. His lab works in animal models of complete spinal cord transections since it is the most challenging to repair.

As Dr. Tuszynski put it, “the adult central nervous system does not spontaneously regenerate [after injury], which is surprising given that it does have its own set of stem cells present throughout.” Their approach to tackle this problem is to put in new stem cells with special growth factors and supportive components to let this process occur.

Just as most patients wouldn’t be able to come in for treatment right away after injury, they don’t start their tests until two weeks after the injury. After that, they inject neural stem cells from either the mouse, rat, or human spinal cord at the injury site and then wait a bit to see if any new connections form. Their group has shown very dramatic increases in both the number of new connections that regenerate from the injury site and extend much further than previous efforts have shown. These connections conduct electrochemical messages as normal neurons do, and over a year later they see no functional decline or tumors forming, which is often a concern when transplanting stem cells that normally like to divide a lot.

While very exciting, he cautions, “this research shows a major opportunity in neural repair that deserves proper study and the best clinical chance to succeed”. He says it requires thorough testing in multiple animal models before going into humans to avoid a case where “a clinical trial fails, not because the biology is wrong, but because the methods need tweaking.”

Everyone needs support – even dying cells

The second great talk was by Dr. Clive Svendsen of Cedars-Sinai Regenerative Medicine Institute on how stem cells might help provide healthy support cells to rescue dying neurons in the brains of patients with neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s. Some ALS cases are hereditary and would be candidates for a treatment using gene editing techniques. However, around 90 percent of ALS cases are “sporadic” meaning there is no known genetic cause. Dr. Svendsen explained how in these cases, a stem cell-based approach to at least fix the cellular cause of the disease, would be the best option.

While neurons often capture all the attention in the brain, since they are the cells that actually send messages that underlie our thoughts and behaviors, the Svendsen lab spends a great deal of time thinking about another type of cell that they think will be a powerhouse in the clinic: astrocytes. Astrocytes are often labeled as the support cells of the brain as they are crucial for maintaining a balance of chemicals to keep neurons healthy and functioning. So Dr. Svendsen reasoned that perhaps astrocytes might unlock a new route to treating neurodegenerative diseases where neurons are unhealthy and losing function.

ALS is a devastating disease that starts with early muscle twitches and leads to complete paralysis and death usually within four years, due to the rapid degeneration of motor neurons that are important for movement all over the body. Svendsen’s team found that by getting astrocytes to secrete a special growth factor, called “GDNF”, they could improve the survival of the neurons that normally die in their model of ALS by five to six times.

After testing this out in several animal models, the first FDA-approved trial to test whether astrocytes from fetal tissue can slow spinal motor neuron loss will begin next month! They will be injecting the precursor cells that can make these GDNF-releasing astrocytes into one leg of ALS patients. That way they can compare leg function and track whether the cells and GDNF are enough to slow the disease progression.

Dr. Svendsen shared with us how long it takes to create and test a treatment that is committed to safety and success for its patients. He says,

Clive Svendsen has been on a 15-year quest to develop an ALS therapy

Clive Svendsen 

“We filed in March 2016, submitted the improvements Oct 2016, and we’re starting our first patient in Feb 2017. [One document is over] 4500 pages… to go to the clinic is a lot of work. Without CIRM’s funding and support we wouldn’t have been able to do this. This isn’t easy. But it is doable!”

 

Improving outcomes in long-term stroke patients in unknown ways

Gary Steinberg

Gary Steinberg

The last speaker for the workshop, Dr. Gary Steinberg, a neurosurgeon at Stanford who is looking to change the lives of patients with severe limitations after having a stroke. The deficits seen after a stroke are thought to be caused by the death of neurons around the area where the stroke occurred, such that whatever functions they were involved with is now impaired. Outcomes can vary for stroke patients depending on how long it takes for them to get to the emergency department, and some people think that there might be a sweet spot for when to start rehabilitative treatments — too late and you might never see dramatic recovery.

But Dr. Steinberg has some evidence that might make those people change their mind. He thinks, “these circuits are not irreversibly damaged. We thought they were but they aren’t… we just need to continue figuring out how to resurrect them.”

He showed stunning videos from his Phase 1/2a clinical trial of several patients who had suffered from a stroke years before walking into his clinic. He tested patients before treatment and showed us videos of their difficulty to perform very basic movements like touching their nose or raising their legs. After carefully injecting into the brain some stem cells taken from donors and then modified to boost their ability to repair damage, he saw a dramatic recovery in some patients as quickly as one day later. A patient who couldn’t lift her leg was holding it up for five whole seconds. She could also touch her arm to her nose, whereas before all she could do was wiggle her thumb. One year later she is even walking, albeit slowly.

He shared another case of a 39 year-old patient who suffered a stroke didn’t want to get married because she felt she’d be embarrassed walking down the aisle, not to mention she couldn’t move her arm. After Dr. Steinberg’s trial, she was able to raise her arm above her head and walk more smoothly, and now, four years later, she is married and recently gave birth to a boy.

But while these studies are incredibly promising, especially for any stroke victims, Dr. Steinberg himself still is not sure exactly how this stem cell treatment works, and the dramatic improvements are not always consistent. He will be continuing his clinical trial to try to better understand what is going on in the injured and recovering brain so he can deliver better care to more patients in the future.

The road to safe and effective therapies using stem cells is long but promising

These were just three of many excellent presentations at the conference, and while these talks involved moving science into human patients for clinical trials, the work described truly stands on the shoulders of all the other research shared at conferences, both present and past. In fact, the reason why scientists gather at conferences is to give one another feedback and to learn from each other to better their own work.

Some of the other exciting talks that are surely laying down the framework for future clinical trials involved research on modeling mini-brains in a dish (so-called cerebral organoids). Researchers like Jürgen Knoblich at the Institute of Molecular Biotechnology in Austria talked about the new ways we can engineer these mini-brains to be more consistent and representative of the real brain. We also heard from really fundamental biology studies trying to understand how one type of cell becomes one vs. another type using the model organism C. elegans (a microscopic, transparent worm) by Dr. Oliver Hobert of Columbia University. Dr. Austin Smith, from the University of Cambridge in the UK, shared the latest about the biology of pluripotent cells that can make any cell type, and Stanford’s Dr. Marius Wernig, one of the meeting’s organizers, told us more of what he’s learned about the road to reprogramming an ordinary skin cell directly into a neuron.

Stay up to date with the latest research on stem cells by continuing to follow this blog and if you’re reading this because you’re considering a stem cell treatment, make sure you find out what’s possible and learn about what to ask by checking out closerlookatstemcells.org.


Samantha Yammine

Samantha Yammine

Samantha Yammine is a science communicator and a PhD candidate in Dr. Derek van der Kooy’s lab at the University of Toronto. You can learn more about Sam and her research on her website.

New approach could help turn back the clock and reverse damage for stroke patients

stroke

Stroke: courtesy WebMD

Stroke is the leading cause of serious, long-term disability in the US. Every year almost 800,000 people suffer from a stroke. The impact on their lives, and the lives of those around them can be devastating.

Right now the only treatment approved by the US Food and Drug Administration (FDA) is tissue plasminogen activator or tPA. This helps dissolve the blood clot causing most strokes and restores blood flow to the brain. However, to be fully effective this has to be administered within about 3-4 hours after the stroke. Many people are unable to get to the hospital in time and as a result suffer long-term damage, damage that for most people has been permanent.

But now a new study in Nature Medicine shows that might not be the case, and that this damage could even be reversible.

The research, done by a team at the University of Southern California (USC) uses a one-two punch combination of stem cells and a protein that helps those cells turn into neurons, the cells in the brain damaged by a stroke.

First, the researchers induced a stroke in mice and then transplanted human neural stem cells alongside the damaged brain tissue. They then added in a dose of the protein 3K3A-APC or a placebo.

hey found that mice treated with 3K3A-APC had 16 times more human stem-cell derived neurons than the mice treated with the placebo. Those neurons weren’t just sitting around doing nothing. USC’s Berislav Zlokovic, senior author of the paper, says they were actively repairing the stroke-induced damage.

“We showed that 3K3A-APC helps the grafted stem cells convert into neurons and make structural and functional connections with the host’s nervous system. No one in the stroke field has ever shown this, so I believe this is going to be the gold standard for future studies. Functional deficits after five weeks of stroke were minimized, and the mice were almost back to normal in terms of motor and sensorimotor functions. Synapses formed between transplanted cells and host cells, so there is functional activation and cooperation of transplanted cells in the host circuitry.”

The researchers wanted to make sure the transplanted cell-3K3A-ACP combination was really the cause of the improvement in the mice so they then used what’s called an “assassin toxin” to kill the neurons they had created. That reversed the improvements in the treated mice, leaving them comparable to the untreated mice. All this suggests the neurons had become an integral part of the mouse’s brain.

So how might this benefit people? You may remember that earlier this summer Stanford researchers produced a paper showing they had helped some 18 stroke patients, by injecting stem cells from donor bone marrow into their brain. The improvements were significant, including in at least one case regaining the ability to walk. We blogged about that work here

In that study, however, the cells did not become neurons nor did they seem to remain in the brain for an extended period. It’s hoped this new work can build on that by giving researchers an additional tool, the 3K3A-ACP protein, to help the transplanted cells convert to neurons and become integrated into the brain.

One of the other advantages of using this protein is that it has already been approved by the FDA for use in people who have experienced an ischemic stroke, which accounts for about 87 percent of all strokes.

The USC team now hope to get approval from the FDA to see if they can replicate their experiences in mice in people, through a Phase 2 clinical trial.

 

 

 

 

 

 

 

What’s the big idea? Or in this case, what’s the 19 big ideas?

supermarket magazineHave you ever stood in line in a supermarket checkout line and browsed through the magazines stacked conveniently at eye level? (of course you have, we all have). They are always filled with attention-grabbing headlines like “5 Ways to a Slimmer You by Christmas” or “Ten Tips for Rock Hard Abs” (that one doesn’t work by the way).

So with those headlines in mind I was tempted to headline our latest Board meeting as: “19 Big Stem Cell Ideas That Could Change Your Life!”. And in truth, some of them might.

The Board voted to invest more than $4 million in funding for 19 big ideas as part of CIRM’s Discovery Inception program. The goal of Inception is to provide seed funding for great, early-stage ideas that may impact the field of human stem cell research but need a little support to test if they work. If they do work out, the money will also enable the researchers to gather the data they’ll need to apply for larger funding opportunities, from CIRM and other institutions, in the future

The applicants were told they didn’t have to have any data to support their belief that the idea would work, but they did have to have a strong scientific rational for why it might

As our President and CEO Randy Mills said in a news release, this is a program that encourages innovative ideas.

Randy Mills, Stem Cell Agency President & CEO

Randy Mills, CIRM President & CEO

“This is a program supporting early stage ideas that have the potential to be ground breaking. We asked scientists to pitch us their best new ideas, things they want to test but that are hard to get funding for. We know not all of these will pan out, but those that do succeed have the potential to advance our understanding of stem cells and hopefully lead to treatments in the future.”

So what are some of these “big” ideas? (Here’s where you can find the full list of those approved for funding and descriptions of what they involve). But here are some highlights.

Alysson Muotri at UC San Diego has identified some anti-retroviral drugs – already approved by the Food and Drug Administration (FDA) – that could help stop inflammation in the brain. This kind of inflammation is an important component in several diseases such as Alzheimer’s, autism, Parkinson’s, Lupus and Multiple Sclerosis. Alysson wants to find out why and how these drugs helps reduce inflammation and how it works. If he is successful it is possible that patients suffering from brain inflammation could immediately benefit from some already available anti-retroviral drugs.

Stanley Carmichael at UC Los Angeles wants to use induced pluripotent stem (iPS) cells – these are adult cells that have been genetically re-programmed so they are capable of becoming any cell in the body – to see if they can help repair the damage caused by a stroke. With stroke the leading cause of adult disability in the US, there is clearly a big need for this kind of big idea.

Holger Willenbring at UC San Francisco wants to use stem cells to create a kind of mini liver, one that can help patients whose own liver is being destroyed by disease. The mini livers could, theoretically, help stabilize a person’s own liver function until a transplant donor becomes available or even help them avoid the need for liver transplantation in the first place. Considering that every year, one in five patients on the US transplant waiting list will die or become too sick for transplantation, this kind of research could have enormous life-saving implications.

We know not all of these ideas will work out. But all of them will help deepen our understanding of how stem cells work and what they can, and can’t, do. Even the best ideas start out small. Our funding gives them a chance to become something truly big.


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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.

Stories of Hope: Stroke

Six months after surviving a stroke, Sonia Olea wanted to die. Her right leg was weak, her right arm useless. She had trouble speaking and even small tasks were challenging. Just making a phone call was virtually impossible. One morning, she woke up with her arm pinned in an awkward, painful position. After finally repositioning it, she wanted to call her fiancé, but knew she couldn’t get the words out. That’s when it hit her.

Sonia has seen first hand how a stroke can rob you of even your most basic abilities.

Sonia has seen first hand how a stroke can rob you of even your most basic abilities.

“I thought, I’m only 32,” says Sonia. “How could this be happening to me?”

Nobody really had an answer. A stroke occurs when a blood clot blocks a vessel in the brain and cuts off blood flow. Brain cells begin to die within minutes when they are deprived of oxygen and nutrients. Stroke rates are on the rise for young adults for a variety of reasons but no one could pinpoint specifically what caused hers.

Slowly, Sonia fought back from her depression and realized she could do this. She would find a way to recover. Just one year later, she got a call from Stanford University; asking if she would be willing to participate in a cutting-edge, stem cell-based clinical trial.

Was she ever. The answer, says Sonia, was a no-brainer.

Rescuing Brain Cells
Led by CIRM grantee Gary Steinberg, M.D., Ph.D., chairman of the Department of Neurosurgery at Stanford School of Medicine, the early phase clinical trial tested the safety of transplanting bone marrow stem cells into the brain. It was a revolutionary approach.

“The old notion was that you couldn’t recover from a stroke after around three months,” says Steinberg. “At that point, the circuits were completely dead—and you couldn’t revive them.”

While this was partially true, it was thought that brain cells, or neurons, just outside the stroke damage might be saved. Steinberg and collaborators at the University of Pittsburgh recognized that stem cells taken from bone marrow wouldn’t transform into functioning neurons. However, the transplanted cells could release molecules that might rescue neurons that were impaired, but not yet dead.

Brain Surgery
Sonia had surgery to transplant bone marrow stem cells into her brain in late May 2013. The improvement was almost instantaneous. “When I woke up, my speech was strong, I could lift up my feet and keep them in the air, I even raised my right hand,” says Sonia. Though the trial was primarily designed to study the stem cell therapy’s safety, researchers were also interested in its effectiveness.

“Sonia was one of our two remarkable patients who got better the day after surgery and continued to improve throughout the year,” says Steinberg. 18 patients in total were treated in that study.

Although Sonia’s treatment results are still very preliminary, they bode well for a separate CIRM-funded stroke research project also led by Steinberg. In this study, cells grown from embryonic stem cells will be turned into early-stage neuron, or brain, cells and then transplanted into the area of stroke damage. The team has found that transplanting these neural cells into mice or rats after a stroke helps the animals regain strength in their limbs. The team is busy working out the best conditions for growing these neural cells in order to take them into clinical trials.

In the meantime, Sonia continues to improve. “My leg is about 95 percent better and my arm is around 60 percent there,” says Sonia. “My speech isn’t perfect, but I can talk and that’s something I never could have done before the surgery.”

The added function has made a huge difference in her quality of life. She can walk, run, drive a car, call a restaurant to make a dinner reservation—simple things she took for granted before having a stroke. But most importantly, she has confidence in the future.

“Everything is good,” says Sonia, “and it’s only going to get better.”

To learn about CIRM-funded stroke research, visit our Stroke Fact Sheet. Read more about Sonia’s Story of Hope on our website.

Stem Cell Stories that Caught our Eye: “Let it Grow” Goes Viral, Stroke Pilot Study, The Bowels of Human Stem Cells, Tumor ‘Safety Lock.’

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.

“Let it Grow” Goes Viral (and National!): Last week on The Stem Cellar we shared one of our favorite student videos from our annual Creativity Program. The video, a parody of the hit song from the movie Frozen, highlighted the outstanding creativity of a group of high school students from City of Hope in Los Angeles. And now, the song has made a splash nationwide—with coverage from ABC 7 Bay Area and even NBC New York!

Students from the City of Hope practice their routine for the group video

Students from the City of Hope practice their routine for the group video

Watch the full video on our YouTube page.

Stroke Pilot Study Shows Promise. Researchers at Imperial College London are currently testing whether stem cells extracted from a patient’s bone marrow can reverse the after effects of a stroke.

Reporting in this week’s Stem Cells Translational Medicine the team, lead by Dr. Soma Banjeree, describe their pilot study in which they collect a type of bone marrow stem cells called CD34+ cells. These cells can give rise to cells that make up the blood and the blood vessel lining. Earlier research suggested that treating stroke victims with these cells can improve recovery after a stroke—not because they replace the brain cells lost during a stroke, but because they release a chemical that triggers brain cells to grow. So the team decided to take the next step with a pilot study of five individuals.

As reported in a recent news release, this initial pilot study was only designed to test the safety of the procedure. But in a surprising twist, all patients in the study also showed significant improvement over a period of six months post-treatment. Even more astonishing, three of the patients (who had suffered one of the most severe forms of stroke) were living assistance-free. But since the first six months after injury is a time when many patients see improved function, these results need to be tested in a controlled trial where not all patients receive the cells

Immediate next steps include using advancing imaging techniques to more closely monitor what exactly happens in the brain after the patients are treated.

Want to learn more about using stem cells to treat stroke? Check out our Stroke Fact Sheet.

Deep in the Bowels of Stem Cell Behavior. Another research advance from UK scientists—this time at Queen Mary University of London researchers—announces important new insight into the behavior of adult stem cells that reside in the human gastro-intestinal tract (which includes the stomach and intestines). As described in a news release, this study, which examined the stem cells in the bowels of healthy individuals, as well as cells from early-stage tumors, points to key differences in their behaviors. The results, published this week in the journal Cell Reports, point to a potential link between stem cell behavior and the development of some forms of cancer.

By measuring the timing and frequency of mutations as they occur over time in aging stem cells, the research team, led by senior author Dr. Trevor Graham, found a key difference in stem cell behaviors between healthy individuals, and those with tumors.

In the healthy bowel, there is a relative stasis in the number of stem cells at any given time. But in cancer, that delicate balance—called a ‘stem cell niche’—appears to get thrown out of whack. There appears to be an increased number of cells, paired with more intense competition. And while these results are preliminary, they mark the first time this complex stem cell behavior has been studied in humans. According to Graham:

“Unearthing how stem cells behave within the human bowel is a big step forward for stem cell research. We now want to use the methods developed in this study to understand how stem cells behave inside bowel cancer, so we can increase our understanding of how bowel cancer grows. This will hopefully shed more light on how we can prevent bowel cancer—the fourth most common cancer in the UK.”

Finding the ‘Safety Lock’ Against Tumor Growth. It’s one of the greatest risks when transplanting stem cells: the possibility that the transplanted cells will grow out of control and form tumors.

But now, scientists from Keio University School of Medicine in Japan have devised an ingenious method that could negate this risk.

Reporting in the latest issue of Cell Transplantation and summarized in a news release, Dr. Masaya Nakamura and his team describe how they transplanted stem cells into the spinal columns of laboratory mice.

And here’s where they switched things up. During the transplantation itself, all mice were receiving immunosuppressant drugs. But then they halted the immunosuppressants in half the mice post-transplantation.

Withdrawing the drugs post-transplantation, according to the team’s findings, had the interesting effect of eliminating the tumor risk, as compared to the group who remained on the drugs. Confirmed with bioluminescent imaging that tracked the implanted cells in both sets of mice, these findings suggest that it in fact may be possible to finely tweak the body’s immune response after stem-cell transplantation.

Want to learn more about stem cells and tumor risk? Check out this recent video from CIRM Grantee Dr. Paul Knoepfler: Paul Knoepfler Talks About the Tendency of Embryonic Stem Cells to Form Tumors.