From bench to bedside: a Q&A with stem cell expert Jan Nolta

At CIRM we are privileged to work with many remarkable people who combine brilliance, compassion and commitment to their search for new therapies to help people in need. One of those who certainly fits that description is UC Davis’ Jan Nolta.

This week the UC Davis Newsroom posted a great interview with Jan. Rather than try and summarize what she says I thought it would be better to let her talk for herself.

Jan Nolta
Jan Nolta

Talking research, unscrupulous clinics, and sustaining the momentum

(SACRAMENTO) —

In 2007, Jan Nolta returned to Northern California from St. Louis to lead what was at the time UC Davis’ brand-new stem cell program. As director of the UC Davis Stem Cell Program and the Institute for Regenerative Cures, she has overseen the opening of the institute, more than $140 million in research grants, and dozens upon dozens of research studies. She recently sat down to answer some questions about regenerative medicine and all the work taking place at UC Davis Health.

Q: Turning stem cells into cures has been your mission and mantra since you founded the program. Can you give us some examples of the most promising research?

I am so excited about our research. We have about 20 different disease-focused teams. That includes physicians, nurses, health care staff, researchers and faculty members, all working to go from the laboratory bench to patient’s bedside with therapies.

Perhaps the most promising and exciting research right now comes from combining blood-forming

stem cells with gene therapy. We’re working in about eight areas right now, and the first cure, something that we definitely can call a stem cell “cure,” is coming from this combined approach.

Soon, doctors will be able to prescribe this type of stem cell therapy. Patients will use their own bone marrow or umbilical cord stem cells. Teams such as ours, working in good manufacturing practice facilities, will make vectors, essentially “biological delivery vehicles,” carrying a good copy of the broken gene. They will be reinserted into a patient’s cells and then infused back into the patient, much like a bone marrow transplant.

“Perhaps the most promising and exciting research right now comes from combining blood-forming stem cells with gene therapy.”

Along with treating the famous bubble baby disease, where I had started my career, this approach looks very promising for sickle cell anemia. We’re hoping to use it to treat several different inherited metabolic diseases. These are conditions characterized by an abnormal build-up of toxic materials in the body’s cells. They interfere with organ and brain function. It’s caused by just a single enzyme. Using the combined stem cell gene therapy, we can effectively put a good copy of the gene for that enzyme back into a patient’s bone marrow stem cells. Then we do a bone marrow transplantation and bring back a person’s normal functioning cells.

The beauty of this therapy is that it can work for the lifetime of a patient. All of the blood cells circulating in a person’s system would be repaired. It’s the number one stem cell cure happening right now. Plus, it’s a therapy that won’t be rejected. These are a patient’s own stem cells. It is just one type of stem cell, and the first that’s being commercialized to change cells throughout the body.

Q: Let’s step back for a moment. In 2004, voters approved Proposition 71. It has funded a majority of the stem cell research here at UC Davis and throughout California. What’s been the impact of that ballot measure and how is it benefiting patients?

We have learned so much about different types of stem cells, and which stem cell will be most appropriate to treat each type of disease. That’s huge. We had to first do that before being able to start actual stem cell therapies. CIRM [California Institute for Regenerative Medicine] has funded Alpha Stem Cell Clinics. We have one of them here at UC Davis and there are only five in the entire state. These are clinics where the patients can go for high-quality clinical stem cell trials approved by the FDA [U.S. Food and Drug Administration]. They don’t need to go to “unapproved clinics” and spend a lot of money. And they actually shouldn’t.

“By the end of this year, we’ll have 50 clinical trials.”

By the end of this year, we’ll have 50 clinical trials [here at UC Davis Health]. There are that many in the works.

Our Alpha Clinic is right next to the hospital. It’s where we’ll be delivering a lot of the immunotherapies, gene therapies and other treatments. In fact, I might even get to personally deliver stem cells to the operating room for a patient. It will be for a clinical trial involving people who have broken their hip. It’s exciting because it feels full circle, from working in the laboratory to bringing stem cells right to the patient’s bedside.

We have ongoing clinical trials for critical limb ischemia, leukemia and, as I mentioned, sickle cell disease. Our disease teams are conducting stem cell clinical trials targeting sarcoma, cellular carcinoma, and treatments for dysphasia [a swallowing disorder], retinopathy [eye condition], Duchenne muscular dystrophy and HIV. It’s all in the works here at UC Davis Health.

There’s also great potential for therapies to help with renal disease and kidney transplants. The latter is really exciting because it’s like a mini bone marrow transplant. A kidney recipient would also get some blood-forming stem cells from the kidney donor so that they can better accept the organ and not reject it. It’s a type of stem cell therapy that could help address the burden of being on a lifelong regime of immunosuppressant drugs after transplantation.

Q: You and your colleagues get calls from family members and patients all the time. They frequently ask about stem cell “miracle” cures. What should people know about unproven treatments and unregulated stem cell clinics?

That’s a great question.The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.

When it comes to advertised therapies: “The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.”

Unfortunately, there are unscrupulous people out there in “unapproved clinics” who prey on desperate people. What they are delivering are probably not even stem cells. They might inject you with your own fat cells, which contain very few stem cells. Or they might use treatments that are not matched to the patient and will be immediately rejected. That’s dangerous. The FDA is shutting these unregulated clinics down one at a time. But it’s like “whack-a-mole”: shut one down and another one pops right up.

On the other hand, the Alpha Clinic is part of our mission is to help the public get to the right therapy, treatment or clinical trial. The big difference between those who make patients pay huge sums of money for unregulated and unproven treatments and UC Davis is that we’re actually using stem cells. We produce them in rigorously regulated cleanroom facilities. They are certified to contain at least 99% stem cells.

Patients and family members can always call us here. We can refer them to a genuine and approved clinical trial. If you don’t get stem cells at the beginning [of the clinical trial] because you’re part of the placebo group, you can get them later. So it’s not risky. The placebo is just saline. I know people are very, very desperate. But there are no miracle cures…yet. Clinical trials, approved by the FDA, are the only way we’re going to develop effective treatments and cures.

Q: Scientific breakthroughs take a lot of patience and time. How do you and your colleagues measure progress and stay motivated?   

Motivation?  “It’s all for the patients.”

It’s all for the patients. There are not good therapies yet for many disorders. But we’re developing them. Every day brings a triumph. Measuring progress means treating a patient in a clinical trial, or developing something in the laboratory, or getting FDA approval. The big one will be getting biological license approval from the FDA, which means a doctor can prescribe a stem cell or gene therapy treatment. Then it can be covered by a patient’s health insurance.

I’m a cancer survivor myself, and I’m also a heart patient. Our amazing team here at UC Davis has kept me alive and in great health. So I understand it from both sides. I understand the desperation of “Where do I go?” and “What do I do right now?” questions. I also understand the science side of things. Progress can feel very, very slow. But everything we do here at the Institute for Regenerative Cures is done with patients in mind, and safety.

We know that each day is so important when you’re watching a loved one suffer. We attend patient events and are part of things like Facebook groups, where people really pour their hearts out. We say to ourselves, “Okay, we must work harder and faster.” That’s our motivation: It’s all the patients and families that we’re going to help who keep us working hard.

Developing a non-toxic approach to bone-crushing cancers

When cancer spreads to the bone the results can be devastating

Battling cancer is always a balancing act. The methods we use – surgery, chemotherapy and radiation – can help remove the tumors but they often come at a price to the patient. In cases where the cancer has spread to the bone the treatments have a limited impact on the disease, but their toxicity can cause devastating problems for the patient. Now, in a CIRM-supported study, researchers at UC Irvine (UCI) have developed a method they say may be able to change that.

Bone metastasis – where cancer starts in one part of the body, say the breast, but spreads to the bones – is one of the most common complications of cancer. It can often result in severe pain, increased risk of fractures and compression of the spine. Tackling them is difficult because some cancer cells can alter the environment around bone, accelerating the destruction of healthy bone cells, and that in turn creates growth factors that stimulate the growth of the cancer. It is a vicious cycle where one problem fuels the other.

Now researchers at UCI have developed a method where they combine engineered mesenchymal stem cells (taken from the bone marrow) with targeting agents. These act like a drug delivery device, offloading different agents that simultaneously attack the cancer but protect the bone.

Weian Zhao; photo courtesy UC Irvine

In a news release Weian Zhao, lead author of the study, said:

“What’s powerful about this strategy is that we deliver a combination of both anti-tumor and anti-bone resorption agents so we can effectively block the vicious circle between cancers and their bone niche. This is a safe and almost nontoxic treatment compared to chemotherapy, which often leaves patients with lifelong issues.”

The research, published in the journal EBioMedicine, has already been shown to be effective in mice. Next, they hope to be able to do the safety tests to enable them to apply to the Food and Drug Administration for permission to test it in people.

The team say if this approach proves effective it might also be used to help treat other bone-related diseases such as osteoporosis and multiple myeloma.

Media matters in spreading the word

Cover of New Yorker article on “The Birth Tissue Profiteers”. Illustration by Ben Jones

When you have a great story to tell the best and most effective way to get it out to the widest audience is still the media, both traditional mainstream and new social media. Recently we have seen three great examples of how that can be done and, hopefully, the benefits that can come from it.

First, let’s go old school. Earlier this month Caroline Chen wrote a wonderful in-depth article about clinics that are cashing in on a gray area in stem cell research. The piece, a collaboration between the New Yorker magazine and ProPublica, focused on the use of amniotic stem cell treatments and the gap between what the clinics who offer it are claiming it can do, and the reality.

Here’s one paragraph profiling a Dr. David Greene, who runs a company providing amniotic fluid to clinics. It’s a fine piece of writing showing how the people behind these therapies blur the lines between fact and reality, not just about the cells but also about themselves:

“Greene said that amniotic stem cells derive their healing power from an ability to develop into any kind of tissue, but he failed to mention that mainstream science does not support his claims. He also did not disclose that he lost his license to practice medicine in 2009, after surgeries he botched resulted in several deaths. Instead, he offered glowing statistics: amniotic stem cells could help the heart beat better, “on average by twenty per cent,” he said. “Over eighty-five per cent of patients benefit exceptionally from the treatment.”

Greene later backpedals on that claim, saying:

“I don’t claim that this is a treatment. I don’t claim that it cures anything. I don’t claim that it’s a permanent fix. All I discuss is maybe, potentially, people can get some improvements from stem-cell care.”

CBS2 TV Chicago

This week CBS2 TV in Chicago did their own investigative story about how the number of local clinics offering unproven and unapproved therapies is on the rise. Reporter Pam Zekman showed how misleading newspaper ads brought in people desperate for something, anything, to ease their arthritis pain.

She interviewed two patients who went to one of those clinics, and ended up out of pocket, and out of luck.

“They said they would regenerate the cartilage,” Patricia Korona recalled. She paid $4500 for injections in her knee, but the pain continued. Later X-rays were ordered by her orthopedic surgeon.

He found bone on bone,” Korona said. “No cartilage grew, which tells me it failed; didn’t work.”

John Zapfel paid $14,000 for stem cell injections on each side of his neck and his shoulder. But an MRI taken by his current doctor showed no improvement.

“They ripped me off, and I was mad.” Zapfel said.      

TV and print reports like this are a great way to highlight the bogus claims made by many of these clinics, and to shine a light on how they use hype to sell hope to people who are in pain and looking for help.

At a time when journalism seems to be increasingly under attack with accusations of “fake news” it’s encouraging to see reporters like these taking the time and news outlets devoting the resources to uncover shady practices and protect vulnerable patients.

But the news isn’t all bad, and the use of social media can help highlight the good news.

That’s what happened yesterday in our latest CIRM Facebook Live “Ask the Stem Cell Team” event. The event focused on the future of stem cell research but also included a really thoughtful look at the progress that’s been made over the last 10-15 years.

We had two great guests, UC Davis stem cell researcher and one of the leading bloggers on the field, Paul Knoepfler PhD; and David Higgins, PhD, a scientist, member of the CIRM Board and a Patient Advocate for Huntington’s Disease. They were able to highlight the challenges of the early years of stem cell research, both globally and here at CIRM, and show how the field has evolved at a remarkable rate in recent years.

Paul Knoepfler

Naturally the subject of the “bogus clinics” came up – Paul has become a national expert on these clinics and is quoted in the New Yorker article – as did the subject of the frustration some people feel at what they consider to be the too-slow pace of progress. As David Higgins noted, we all think it’s too slow, but we are not going to race recklessly ahead in search of something that might heal if we might also end up doing something that might kill.

David Higgins

A portion of the discussion focused on funding and, in particular, what happens if CIRM is no longer around to fund the most promising research in California. We are due to run out of funding for new projects by the end of this year, and without a re-infusion of funds we will be pretty much closing our doors by the end of 2020. Both Paul and David felt that could be disastrous for the field here in California, depriving the most promising projects of support at a time when they needed it most.

It’s probably not too surprising that three people so closely connected to CIRM (Paul has received funding from us in the past) would conclude that CIRM is needed for stem cell research to not just survive but thrive in California.

A word of caution before you watch: fashion conscious people may be appalled at how my pocket handkerchief took on a life of its own.

Stories that caught our eye: FDA grants orphan drug status to CIRM-funded therapy; stunning discovery upends ideas of cell formation; and how tadpoles grow new tails

Gut busting discovery

Intestinal stem cells: Photo courtesy Klaus Kaestner, Penn Institute for Regenerative Medicine

It’s not often you read the word “sensational” in a news release about stem cells. But this week researchers at the University of Copenhagen released findings that are overturning long-held ideas about the development of cells in our stomachs. So perhaps calling it “sensational” is not too big a stretch.

In the past it was believed that the development of immature cells in our stomachs, before a baby is born, was predetermined, that the cells had some kind of innate sense of what they were going to become and when. Turns out that’s not the case. The researchers say it’s the cells’ environment that determines what they will become and that all cells in the fetus’ gut have the potential to turn into stem cells.

In the “sensational” news release lead author, Kim Jensen, says this finding could help in the development of new therapies.

“We used to believe that a cell’s potential for becoming a stem cell was predetermined, but our new results show that all immature cells have the same probability for becoming stem cells in the fully developed organ. In principle, it is simply a matter of being in the right place at the right time. Here signals from the cells’ surroundings determine their fate. If we are able to identify the signals that are necessary for the immature cell to develop into a stem cell, it will be easier for us to manipulate cells in the wanted direction’.

The study is published in the journal Nature.                             

A tale of a tail

African clawed frog tadpole: Photo courtesy Gary Nafis

It’s long been known that some lizards and other mammals can regrow severed limbs, but it hasn’t been clear how. Now scientists at the University of Cambridge in the UK have figured out what’s going on.

Using single-cell genomics the scientists were able to track which genes are turned on and off at particular times, allowing them to watch what happens inside the tail of the African clawed frog tadpole as it regenerates the damaged limb.

They found that the response was orchestrated by a group of skin cells they called Regeneration-Organizing Cells, or ROCs. Can Aztekin, one of the lead authors of the study in the journal Science, says seeing how ROCs work could lead to new ideas on how to stimulate similar regeneration in other mammals.

“It’s an astonishing process to watch unfold. After tail amputation, ROCs migrate from the body to the wound and secrete a cocktail of growth factors that coordinate the response of tissue precursor cells. These cells then work together to regenerate a tail of the right size, pattern and cell composition.”

Orphan Drug Designation for CIRM-funded therapy

Poseida Therapeutics got some good news recently about their CIRM-funded therapy for multiple myeloma. The US Food and Drug Administration (FDA) granted them orphan drug designation.

Orphan drug designation is given to therapies targeting rare diseases or disorders that affect fewer than 200,000 people in the U.S. It means the company may be eligible for grant funding toward clinical trial costs, tax advantages, FDA user-fee benefits and seven years of market exclusivity in the United States following marketing approval by the FDA.

CIRM’s President and CEO, Dr. Maria Millan, says the company is using a gene-modified cell therapy approach to help people who are not responding to traditional approaches.

“Poseida’s technology is seeking to destroy these cancerous myeloma cells with an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells.”

Poseida’s CEO, Eric Ostertag, said the designation is an important milestone for the company therapy which “has demonstrated outstanding potency, with strikingly low rates of toxicity in our phase 1 clinical trial. In fact, the FDA has approved fully outpatient dosing in our Phase 2 trial starting in the second quarter of 2019.”

Stem cell stories that caught our eye: CIRM-funded scientist wins prestigious prize and a tooth trifecta

CIRM-grantee wins prestigious research award

Do we know how to pick ‘em or what? For a number of years now we have been funding the work of Stanford’s Dr. Marius Wernig, who is doing groundbreaking work in helping advance stem cell research. Just how groundbreaking was emphasized this week when he was named as the winner of the 2018 Ogawa-Yamanaka Stem Cell Prize.

WernigMarius_Stanford

Marius Wernig, MD, PhD. [Photo: Stanford University]

The prestigious award, from San Francisco’s Gladstone Institutes, honors Wernig for his innovative work in developing a faster, more direct method of turning ordinary cells into, for example, brain cells, and for his work advancing the development of disease models for diseases of the brain and skin disorders.

Dr. Deepak Srivastava, the President of Gladstone, announced the award in a news release:

“Dr. Wernig is a leader in his field with extraordinary accomplishments in stem cell reprogramming. His team was the first to develop neuronal cells reprogrammed directly from skin cells. He is now investigating therapeutic gene targeting and cell transplantation–based strategies for diseases with mutations in a single gene.”

Wernig was understandably delighted at the news:

“It is a great honor to receive this esteemed prize. My lab’s goal is to discover novel biology using reprogrammed cells that aids in the development of effective treatments.”

Wernig will be presented with the award, and a check for $150,000, at a ceremony on Oct. 15 at the Gladstone Institutes in San Francisco.

A stem cell trifecta for teeth research

It was a tooth trifecta among stem cell scientists this week. At Tufts University School of Medicine, researchers made an important advance in the development of bioengineered teeth. The current standard for tooth replacement is a dental implant. This screw-shaped device acts as an artificial tooth root that’s inserted into the jawbone. Implants have been used for 30 years and though successful they can lead to implant failure since they lack many of the properties of natural teeth. By implanting postnatal dental cells along with a gel material into mice, the team demonstrated, in a Journal of Dental Research report, the development of natural tooth buds. As explained in Dentistry Today, these teeth “include features resembling natural tooth buds such as the dental epithelial stem cell niche, enamel knot signaling centers, transient amplifying cells, and mineralized dental tissue formation.”

Another challenge with the development of a bioengineered tooth replacement is reestablishing nerve connections within the tooth, which plays a critical role in its function and protection but doesn’t occur spontaneously after an injury. A research team across the “Pond” at the French National Institute of Health and Medical Research, showed that bone marrow-derived mesenchymal stem cells in the presence of a nerve fiber can help the nerve cells make connections with bioengineered teeth. The study was also published in the Journal of Dental Research.

And finally, a research report about stem cells and the dreaded root canal. When the living soft tissue, or dental pulp, of a tooth becomes infected, the primary course of action is the removal of that tissue via a root canal. The big downside to this procedure is that it leaves the patient with a dead tooth which can be susceptible to future infections. To combat this side effect, researchers at the New Jersey Institute of Technology report the development of a potential remedy: a gel containing a fragment of a protein that stimulates the growth of new blood vessels as well as a fragment of a protein that spurs dental stem cells to divide and grow. Though this technology is still at an early stage, it promises to help keep teeth alive and healthy after root canal. The study was presented this week at the National Meeting of the American Chemical Society.

Here’s an animated video that helps explain the research:

New Study on Humans Shows Promise for Sepsis Therapy

A new study published in STEM CELLS, conducted by researchers at the University of Amsterdam, shows how mesenchymal stem cells (MSCs) can restore the health and improve the function of the immune system,  which could benefit the treatment of sepsis. Sepsis is a life-threatening complication from an infection that can lead to multiple organ failure. It is a major cause of illness and death worldwide and despite the use of antibiotics it kills about one in every four patients who contract it.

Since early studies done on animals have shown that treating sepsis with MSCs can reduce the mortality rate by as much as 73 percent, a group of researchers from University of Amsterdam sought to answer this question:  could humans realize the same benefits?

So, the team conducted an experiment by taking a group of healthy volunteers and inducing endotoxemia in them, where bacterial toxins can build up and cause fever, nausea and vomiting but do not cause long-term harm to the participants (?).  The idea was that by inducing endotoxemia, which exhibits some of the key characteristics of sepsis, that they could model the condition in people.

One hour prior to the initial dose, each person was given an infusion of either adipose (fat) mesenchymal stem cells (ACSs) taken from a donor,  or a placebo as a control. Those receiving the ASCs were divided into three groups, with each group receiving a consecutively higher dose of cells.

In a news release, Desiree Perlee, senior author of the study, said the study provided some valuable insights and information:

gI_100288_foto_perlee.png

Desirée Perlee

“The results showed that the ASCs were well tolerated…We realize that there is a limitation with the endotoxemia model. Although in a qualitative way it resembles responses seen in patients with sepsis, it differs in that sepsis-associated alterations are more severe and sustained, while in the endotoxemia model responses occur in a very rapid, short-lived and transient way. But despite these limitations, some of our findings confirm the earlier studies on animals. We believe they show further testing of ASCs in actual sepsis patients is warranted.”

Dr. Jan Nolta, Editor-in-Chief of STEM CELLS (and a CIRM-grantee), said, “This novel clinical trial provides important insight into the mechanism of action of MSCs in inflammation and provides human safety data in support of treatment of sepsis using MSCs.

 

The Five Types of Stem Cells

When I give an “Intro to Stem Cells” presentation to, say, high school students or to a local Rotary Club, I begin by explaining that there are three main types of stem cells: (1) embryonic stem cells (ESCs) (2) adult stem cells and (3) induced pluripotent stem cells (iPSCs). Well, like most things in science, it’s actually not that simple.

To delve a little deeper into the details of characterizing stem cells, I recommend checking out a video animation produced by BioInformant, a stem cell market research company. The video is introduced in a blog, “Do you know the 5 types of stem cells?” by Cade Hildreth, BioInformant’s founder and president.

Stem-Cell-Types

Image credit: BioInformant

Hildreth’s list categorizes stem cells by the extent of each type’s shape-shifting abilities. So while we sometimes place ESCs and iPSCs in different buckets because the methods for obtaining them are very different, in this list, they both belong to the pluripotent stem cell type. Pluri (“many”) – potent (“potential”) refers to the ability of both stem cell types to specialize into all of the cell types in the body. They can’t, though, make the cells of the placenta and other extra-embryonic cells too. Those ultimate blank-slate stem cells are called toti (“total”) – potent (“potential”).

When it comes to describing adult stem cells in my talks, I often lump blood stem cells together with muscle stem cells because they are stem cells that are present within us throughout life. But based on their ability to mature into specialized cells, these two stem cell types fall into two different categories in Hildreth’s list:  blood stem cells which can specialize into closely related cell types – the various cell types found in the blood – are considered “oligopotent” while muscle stem cells are “unipotent” because the can only mature into one type of cell, a muscle cell.

For more details on the five types of stem cells based on their potential to specialize, head over to the BioInformant blog. And scroll to the very bottom for the video animation which can also viewed on FaceBook.

Starving stem cells of oxygen can help build stronger bones

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J. Kent Leach: Photo courtesy UC Davis

We usually think that starving something of oxygen is going to make it weaker and maybe even kill it. But a new study by J. Kent Leach at UC Davis shows that instead of weakening bone defects, depriving them of oxygen might help boost their ability to create new bone or repair existing bone.

Leach says in the past the use of stem cells to repair damaged or defective bone had limited success because the stem cells often didn’t engraft in the bone or survive long if they did. That was because the cells were being placed in an environment that lacked oxygen (concentration levels in bone range from 3% to 8%) so the cells found it hard to survive.

However, studies in the lab had shown that if you preconditioned mesenchymal stem cells (MSCs), by exposing them to low oxygen levels before you placed them on the injury site, you helped prolong their viability. That was further enhanced by forming the MSCs into three dimensional clumps called spheroids.

Lightbulb goes off

In the  current study, published in Stem Cells, Leach says the earlier spheroid results  gave him an idea:

“We hypothesized that preconditioning MSCs in hypoxic (low oxygen) culture before spheroid formation would increase cell viability, proangiogenic potential (ability to create new blood vessels), and resultant bone repair compared with that of individual MSCs.”

So, the researchers placed one group of human MSCs, taken from bone marrow, in a dish with just 1% oxygen, and another identical group of MSCs in a dish with normal oxygen levels. After three days both groups were formed into spheroids and placed in an alginate hydrogel, a biopolymer derived from brown seaweed that is often used to build cellular cultures.

Seaweed

Brown seaweed

The team found that the oxygen-starved cells lasted longer than the ones left in normal oxygen, and the longer those cells were deprived of oxygen the better they did.

Theory is great, how does it work in practice?

Next was to see how those two groups did in actually repairing bones in rats. Leach says the results were encouraging:

“Once again, the oxygen-deprived, spheroid-containing gels induced significantly more bone healing than did gels containing either preconditioned individual MSCs or acellular gels.”

The team say this shows the use of these oxygen-starved cells could be an effective approach to repairing hard-to-heal bone injuries in people.

“Short‐term exposure to low oxygen primes MSCs for survival and initiates angiogenesis (the development of new blood vessels). Furthermore, these pathways are sustained through cell‐cell signaling following spheroid formation. Hypoxic (low oxygen) preconditioning of MSCs, in synergy with transplantation of cells as spheroids, should be considered for cell‐based therapies to promote cell survival, angiogenesis, and bone formation.”

CIRM & Dr. Leach

While CIRM did not fund this study we have invested more than $1.8 million in another study Dr. Leach is doing to develop a new kind of imaging technology that will help us see more clearly what is happening in bone and cartilage-targeted therapies.

In addition, back in March of 2012, Dr. Leach spoke to the CIRM Board about his work developing new approaches to growing bone.

 

A Cowboys Fan’s Take on The Catch and Dwight Clark’s Passing Due to ALS

I grew up in Dallas in the 80’s. Needless to say, I was a diehard fan of the Dallas Cowboys National Football League (NFL) team and January 10, 1982 will forever be seared into my memory. Late in the fourth quarter, the Cowboys were leading the San Francisco 49ers 27-21 in the conference championship with the winner moving on to the Super Bowl. But then, with less than a minute remaining, The Catch happened. Dwight Clark of the 49ers sailed over the Cowboys’ Everson Walls to catch Joe Montana’s game-winning pass in the end zone. I was crushed and had a dark cloud over my head for many days afterward.

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Dwight Clark sails over Everson Walls for The Catch

Though I’ve lived in the Bay Area for the past twenty years and become a 49ers fan, it’s still hard for me to watch video clips of The Catch which is arguably this region’s greatest moment in the history of professional sports. Over the years of listening to sports talk radio, I heard interviews with and about Dwight Clark and have come to realize what a terrific person he was. So, I may hate that play, but I certainly can’t hate the man. That’s why I was as heartbroken as everyone else around here with yesterday’s news that Clark had succumbed, at only 61 years of age, to his battle with amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease, an incurable neurodegenerative disorder that is usually fatal within 2 to 5 years after diagnosis.

Not surprisingly, the ALS Association’s Golden West Chapter, which covers the entire West Coast, was contacted by every Bay Area TV station about Clark’s death. In her KTVU news segment, TV reporter Deborah Villalon explained what Clark meant to ALS patient advocates who often feel invisible:

“To the ALS community he is a hero for raising awareness in the very public way he faced the disease. Clark faced the terminal illness head-on, speaking publicly of his challenges, even appearing on the big screen at Levi’s Stadium last fall, to thank fans for their support.”

At CIRM, we are funding two clinical trials run by Cedars-Sinai and BrainStorm Cell Therapeutics testing stem cell-based treatments for ALS. In Clark’s memory and for everyone in the ALS community, we hope these trials one day lead to new treatment options for the 5,000 thousand newly diagnosed cases each year in the U.S.

Can stem cells help people recover from a stroke? Join us for a Facebook Live event this Thursday, May 31 for the answers

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Stroke is one of the leading causes of death in the US and the leading cause of serious, long-term disability. But could stem cell therapies change that and help people who’ve had a brain attack?  Could stem cells help repair the damage caused by a stroke and restore a person’s ability to speak normally, to be able to walk without a limp or regain strength in their hands and arms?

To find out the answers to these and other questions joins us for “Ask the Expert”, a special Facebook Live event this Thursday, May 31, from noon till 1pm PDT

 The event will feature Dr. Gary Steinberg, the Chair of Neurosurgery at Stanford University. Dr. Steinberg is currently running a CIRM-funded clinical trial targeting stroke.

We will also be joined by CIRM Senior Science Officer Lila Collins, PhD who can talk about the broad range of other projects using stem cells to help people recover from a stroke.

We are also delighted to welcome Sonia Coontz, who suffered a devastating stroke several years ago and made a remarkable recovery after getting a stem cell therapy.

To join us for the event, all you have to do is go to our Facebook page on Thursday at noon (PDT) and you should see a video playing, which you can watch on mobile or desktop. Click the video to enter viewing mode.

Also, make sure to “like” our page before the event to receive a notification that we’ve gone live.

And we want to hear from you, so you will be able to post questions for the experts to answer or, you can email them directly to us at info@cirm.ca.gov

We look forward to seeing you there.