CIRM-Funded Scientists Make New Progress Toward Engineering a Human Esophagus

Creating tissues and organs from stem cells—often referred to as ‘tissue engineering’—is hard. But new research has discovered that the process may in fact be a little easier than we once thought, at least in some situations.

Engineered human esophageal tissue [Credit: The Saban Research Institute].

Engineered human esophageal tissue [Credit: The Saban Research Institute].

Last week, scientists at The Saban Research Institute of Children’s Hospital Los Angeles announced that the esophagus—the tube that transports food, liquid and saliva between the mouth and the stomach—can be grown inside animal models after injecting the right mix of early-stage, or ‘progenitor,’ esophageal cells.

These findings, published in the journal Tissue Engineering Part A, are an important step towards generating tissues and organs that have been damaged due to disease or—in some cases—never existed in the first place.

According to stem cell researcher Tracy Grikscheit, who led the CIRM-funded study, the researchers first implanted a biodegradable ‘scaffold’ into laboratory mice. They then injected human progenitor cells into the mice and watched as they first traveled to the correct location—and then began to grow. The ability to both migrate to the right location and differentiate into the right cell type, without the need for any external coaxing, is crucial if scientists are to successfully engineer such a critical type of tissue.

“Different progenitor cells can find the right ‘partner’ in order to grow into specific esophageal cell types—and without the need for [outside] growth factors,” explained Grikscheit in a news release. “This means that successful tissue engineering of the esophagus is simpler than we previously thought.”

Grikscheit, who is also a pediatric surgeon as Children’s Hospital Los Angeles, was particularly hopeful with how their findings might one day be used to treat children born with portions of the esophagus missing—as well as adults suffering from esophageal cancer, the fastest-growing cancer in the U.S.

“We have demonstrated that a simple and versatile, biodegradable polymer is sufficient for the growth of a tissue-engineered esophagus from human cells. This not only serves as a potential source of tissue, but also a source of knowledge—as there are no other robust models available for studying esophageal stem cell dynamics.”

Want to learn more about tissue engineering? Check out these video highlights from a recent CIRM Workshop on the field.

Meeting designed to bring together investors and researchers seemed to hit pay dirt this year

When I helped plan the first Partnering Forum at the Stem Cell Meeting on the Mesa four years ago, I must admit it felt a bit early for the stated goal of the meeting, which was to bring together academic research teams and early stage biotech companies with big pharmaceutical companies and other investors who could help take the therapies to the patients. The air of the resulting meeting was excitement moderated by caution and a healthy dose of skepticism.

This year’s even that ended yesterday felt very different. First it grew from a couple hundred to more than 700. It followed a period that saw a series of major investments in the field. One speaker noted that in the previous 12 months, $2.5 billion had been invested in cell and gene therapies, double the amount of the prior 12 months. At one panel discussion, a venture capital executive announced that his company was ready to invest in one of our grantees. He had seen them present their research in prior years and their project was not ready then, but it is now.

A panel on regulatory hurdles to advancing cell therapies, including CIRM senior VP Ellen Feigal (second from left) talked about the need for the community to share information.

A panel on regulatory hurdles to advancing cell therapies, including CIRM senior VP Ellen Feigal (second from left) talked about the need for the community to share information.

Many speakers still called for caution, but at a different level. Several companies are expected to report results from Phase 3 clinical trials—the large late stage trials that decide if a therapy is ready for marketing—and they noted that the industry needs good results from some of those trials. A frequent refrain voiced the need for clear data on clinical outcome that makes it easy to show a superior benefit for patients compared to what’s available today.

Our President and CEO Randal Mills led off the second day of the event with a discussion of the restructuring of our grant making process that he refers to as “CIRM 2.0.” His goal is to cut the time from eligibility to submit a grant to the time it is awarded from the current average of 22 months to just 81 days. The concept created an immediate buzz in the room that lasted through lunch three hours later.

But as Randy likes to say, “It is all about the patients.” He noted in his presentation that in his prior position, working on a stem cell therapy for pediatric Graft Versus Host Disease—a horrible deadly complication that strikes half of kids getting bone marrow transplants for cancer—that extra 20 months equals another 750 dying kids.

Everyone here seemed to be in sync on reducing the time to develop therapies. If someone produced a word map of the event, “accelerate” would be large and near the middle as one of the most spoken words.

Don Gibbons

Seventh annual Stem Cell Awareness Day, Oct. 8, will share some of the reasons behind the hope

When we organized the first Stem Cell Awareness Day in 2008 it was a small affair with events in Australia, Canada and a couple venues in California. It has quickly grown to become a sufficiently grass roots event worldwide that we can’t capture all the activities. But we feature 10 events in the US and six international events at our web site stemcellday.com.

Last year's Stem Cell Day event at the Sanford Consortium in San Diego drew a full house.

Last year’s Stem Cell Day event at the Sanford Consortium in San Diego drew a full house.

One entry in particular is truly international: the opening of a science museum exhibit “Super Cells” in Canada before it embarks on a five-year tour across North America, the United Kingdom, and potentially Europe as well. We wrote about the exhibit that CIRM helped to develop last week.

One event that fully embraces the spirit of the day this year will be at the annual Stem Cell Meeting on the Mesa in La Jolla, California. All the various players in the field, researchers, industry executives and investors come together at this annual gather on the famous La Jolla mesa to foster partnerships that can accelerate the movement of discoveries into therapies for patients. These international leaders will be joined by the public at an event on the second night of the meeting. The featured speaker will be Carl June, a real star of one of the field’s breakthrough therapies: using genes to modify cells to treat cancer and HIV.

In California, CIRM-funded institutions in San Diego, Irvine, Los Angeles, Berkeley and Sacramento will be hosting lab tours, seminars and other events for the public. We will also be matching CIRM grantees with high schools up and down the state to offer guests talks on stem cell science. We expect to reach at least 50 classes and more than a thousand students. Similar efforts are taking place in Toronto, Canada and in New York State.

Many of the activities today and throughout the month—we consider all of October a time to share stem cell knowledge—are focused on the general public. A list of those we are aware of can be found on the Stem Cell Awareness Day website.
If you can’t make one of these events but want to discover more about stem cells, here are a few of our best resources:
stem cell basics
Disease fact sheets
A list of our therapies in development

This year attendees at all the events are likely to hear much more than in previous years about potential therapies that have made it through the pipeline and are now being tested (or close to being tested) in patients. The promise and hope of stem cell science is starting to be backed up by data.

Don Gibbons

See You Next Week: 2014 Stem Cell Meeting on the Mesa

Next week marks the fourth annual Stem Cell Meeting on the Mesa (SCMOM) Partnering Forum in La Jolla, California and CIRM , one of the main organizers, hopes to see you there.

SCMOM

SCMOM is the first and only meeting organized specifically for the regenerative medicine and cell therapy sectors. The meeting’s unique Partnering Forum brings together a network of companies—including large pharma, investors, research institutes, government agencies and philanthropies seeking opportunities to expand key relationships in the field. The meeting will feature presentations by 50 leading companies in the fields of cell therapy, gene therapy and tissue engineering.

Co-founded by CIRM and the Alliance for Regenerative Medicine (ARM), SCMOM has since grown both in participants and in quality. As Geoff MacKay, President and CEO of Organogenesis, Inc. and ARM’s Chairman, stated in a recent news release:

“This year the Partnering Forum has expanded to include an emphasis not only on cell therapies, but also gene and gene-modified cell therapy technologies. This, like the recent formation of ARM’s Gene Therapy Section, is a natural progression for the meeting as the advanced therapies sector expands.”

This year CIRM President and CEO Dr. C. Randal Mills, as well as Senior Vice President, Research & Development Dr. Ellen Feigal will be speaking to attendees. In addition, 12 CIRM grantees will be among the distinguished speakers, including Drs. Jill Helms, Don Kohn and Clive Svendsen, as well as leaders from Capricor, Asterias, ViaCyte, Sangamo Biosciences and others.

CIRM has made tremendous progress advancing stem cell therapies to patients and expects to have ten approved clinical trials by the end of 2014. The trials which span a variety of therapeutic areas using several therapeutic strategies such as cell therapy, monoclonal antibodies and small molecules are increasingly being partnered with major industry players. CIRM still has more than $1 billion to invest and is interested in co-funding with industry and investors—don’t miss the chance to strike the next partnership at SCMOM next week.

For more details and to view the agenda, please visit: http://stemcellmeetingonthemesa.com/

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.

Stories of Hope: Spinal Cord Injury

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.

Katie Sharify had six days to decide: would she let her broken body become experimental territory for a revolutionary new approach—even if it was unlikely to do her any good? The question was barely fathomable. She had only just regained consciousness. A week earlier, she had been in a car crash that damaged her spine, leaving her with no sensation from the chest down. In the confusion and emotion of those first few days, the family thought that the treatment would fix Katie’s mangled spinal cord. But that was never the goal. The objective, in fact, was simply to test the safety of the treatment. The misunderstanding – a cure, and then no cure — plunged the 23-year-old from hope to despair. And yet she couldn’t let the idea of this experimental approach go.

Katie never gave up hope that stem cell-based therapies could help her or others like her living with spinal cord injury.

Katie never gave up hope that stem cell-based therapies could help her or others like her living with spinal cord injury.

Just days after learning that she would never walk again, that she would never know when her bladder was full, that she would not feel it if she broke her ankle, she was thinking about the next girl who might lie in this bed with a spinal injury. If Katie walked away from this experimental approach—what would happen to others that came after her?

Her medical team provided a crash course in stem cell therapy to help Katie think things through. In this case the team had taken stem cells obtained from a five-day old embryo and converted them into cells that support communication between the brain and body. Those cells would be transplanted into the injured spines. Earlier experiments in animal models suggested that, once in place, these cells might help regenerate a patient’s own nerve tissue. But before scientists could do the experiment, they needed to make sure the technique they were using was safe by using a small number of cells, too few to likely have any benefit. And that’s why they wanted Katie’s help in this CIRM-funded trial. They explained the risks. They explained that she was unlikely to derive any benefit. They explained that she was just a step along the way. Even so, Katie agreed. She became the fifth patient in what’s called a Phase I trial: part of the long, arduous process required to bring new therapies to patients. Shortly after she was treated the trial stopped enrolling patients for financial reasons.

That was nearly three years ago. Since then, she has been through an intensive physical therapy program to increase her strength. She went back to college. She tried skiing and surfing. She learned how to make life work in this new body. But as she rebuilt her life she wondered if taking part in the clinical trial had truly made a difference.

“I was frustrated at first. I felt hopeless. Why did I even do this? Why did I even bother?” But soon she began to see how small advances were moving the science forward. She learned the steep challenges that await new therapies. Then this year, she discovered that the research she participated in was deemed to be safe and is about to enter its next phase, thanks to a $14.3 million grant from CIRM to Asterias Biotherapeutics. “This has been my wish from day one,” Katie says.

“It gives me so much hope to know there is an organization that cares and wants to push these therapies forward, that wants to find a cure or a treatment,” she says. “I don’t know what I would do if I thought nobody cared, nobody wanted to take any risks, nobody wanted to put any funding into spinal cord injuries.

“I really have to have some ray of hope to hold onto, and for me, CIRM is that ray of hope.”

For more information about CIRM-funded spinal cord injury research, visit our Spinal Cord Injury Fact Sheet. You can read more about Katie’s Story of Hope on our website.

CIRM 2.0: How to Build a Better Stem Cell Agency and Speed up Treatments to Patients

Change is never easy. We all get used to doing things in a certain way and it can sometimes be difficult to realize that the way we have chosen, while it may have worked well at one time is perhaps not the best way to achieve our goals at this time. Well, change is coming to the stem cell agency.

CIRM_LogoColor2_L_web_540x216

It’s not surprising that our new President & CEO, C. Randal Mills, Ph.D., would want to introduce some of his own ideas about how best to run the agency in the current moment of stem cell science. After all, it’s those ideas that landed him the job in the first place. Now Randy wants us to develop a clearer focus, one that is more aligned with his 4-point criteria for assessing everything we do.

  1. Will it speed up treatments to patients
  2. Will it increase the likelihood of successful treatments for patients
  3. Does it target an unmet medical need
  4. Is it efficient.

That new focus begins with re-imagining how we can be most effective in the way we fund research. Right now we put out what’s called an RFA or Request for Application, telling people who have promising projects in a particular area of stem cell research to submit an application and if they are successful they’ll get up to $20 million, depending on the kind of project.

The problem is, we often have long gaps between each round of funding and so a company or institution with a promising therapy will sometimes have to wait as much as a couple of years before they can apply again. If they do wait and are successful in their application it could still be another year or two before they are able to gain actual funding and begin a clinical trial. But when lives are at stake, you can’t afford to wait that long. So we’re looking at ways of speeding things up, making it easier for the best science to get the funds needed when they are needed.

At our Board meeting yesterday Randy outlined some broad concepts about what he wants to do and how it can be done. It’s part of his vision for the agency, a new focus that he is calling CIRM 2.0 (with acknowledgments to Dr. Paul Knoepfler who coined the term earlier this year)

As with any simple idea it’s really complicated. We need to achieve greater speed, to streamline the way we do things, without sacrificing the quality of the review process because we need to ensure that we only fund the best science.

In the months to come, as the precise details about these proposed changes are fine tuned, the Board will hear in greater detail how this will work and, as always, it will be up to them to decide if they think it’s a good idea.

Either way it will start a conversation about how we can become more efficient and more effective at living up to our mission, of accelerating therapies that target patients with unmet medical needs. And that always has to be a good thing.

For more details about the other big events at yesterday’s Board meeting, including awarding $16 million to ViaCyte to help it advance its promising therapy for type 1 diabetes, you can read the news release posted on our website.

Stories of Hope: Leukemia

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.

Stem cells create life. But if things go wrong, they can also threaten it. Theresa Blanda found that out the hard way. Fortunately for her, CIRM-funded research helped her fight this threat, and get her life back.

Theresa's battle with leukemia took a happier turn after entering into a stem cell-based clinical trial.

Theresa’s battle with leukemia took a happier turn after entering into a stem cell-based clinical trial.

In the first few days of human development embryonic stem cells are a blank slate; they don’t yet have a special, defined role, but have potential. The potential to turn into the cells that make up our kidneys, heart, brain, every other organ and every tissue in our body. Because of this flexibility, stem cells have shown great promise as a way to regenerate dead, diseased or injured tissue to treat many life-threatening or chronic conditions.

But some studies have suggested a secret, darker side to stem cells—so-called cancer stem cells. Like their embryonic cousins, these cells have the ability to both self-renew— to divide and make more copies of themselves – and specialize into other cell types. Many researchers believe they can serve as a reservoir for cancer, constantly reinvigorating tumors, helping them spread throughout the body. To complicate matters, these slow-growing cells are often impervious to cancer therapies, enabling them to survive chemotherapy.

For Theresa Blanda, cancer stem cells were dragging her down a slippery slope towards disease and possibly death. In 2003, she was diagnosed with polycythemia vera (CV), which causes the body to produce too many red blood cells. As sometimes happens with CV patients, her body began producing too many white blood cells as well. Eventually, she developed an even more serious condition, myelofibrosis, a form of bone marrow scarring that results in an enlarged spleen, bone pain, knee swelling and other debilitating symptoms.

“You couldn’t even breathe my way or I’d bruise,” says Theresa. “I didn’t think I was going to make it.”

Her doctors wanted to do a bone marrow transplant, but were having difficulty finding the right donor. “Finally, I just asked if there was some kind of clinical trial that could help me,” says Theresa.

Fortunately, there was.

The Root Cause
At UC San Diego’s Moores Cancer Center, Catriona Jamieson, M.D., Ph.D., had made a discovery that would have a big impact on Theresa’s health. In research funded in part by CIRM, Jamieson found a key mutation in blood-forming stem cells. Specifically, a mutation in a gene called JAK2 was being passed on to Theresa’s entire blood system, causing CV and myelofibrosis. Without effective treatment, her condition could have progressed into acute myeloid leukemia, a blood cancer with a very poor survival rate.

“These malignant stem cells create an inhospitable environment for regular stem cells, suppressing normal blood formation,” says Jamieson. “We needed to get rid of these mutated stem cells so the normal ones could breathe a sigh of relief.”

The answer was a JAK2 inhibitor being developed by San Diego-based TargeGen. Though the trial had already started, they made room for Theresa and the results were amazing. Within weeks, her discomfort had faded, her spleen had returned to normal and she was back at work.

“In a month or two I was feeling pretty good,” says Theresa. “I could climb stairs and the swelling in my knee had gone down.”

She continued on the drug for five years but safety issues forced the trial to be suspended. But the work continues. With continued support from CIRM, Jamieson and others are investigating new JAK2 inhibitors, and other alternatives, to help myelofibrosis patients.

“Because of CIRM funding, we’ve managed to develop a number of agents that have gone into clinical trials,” says Jamieson. “That means patients have lived to hold their grandchildren, attend their mom’s hundredth birthday party and live fruitful lives.”

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

September ICOC Boarding Meeting Begins Soon

The September ICOC Boarding Meeting begins this morning in Berkeley, CA.

The complete agenda can be found here, including a special Spotlight on Disease focusing on Inflammatory Bowel Disease.

For those not able to attend, feel free to dial in:

Dial in Infomation:

United States: (800) 230-1093
Access Code: 334835

WEB MEETING ACCESS INFORMATION:
——————————-
* https://www.webmeeting.att.com
* Meeting Number(s): 5114686455
* PARTICIPANT CODE: 313650

WEBEX LINK:
1. Go to https://cirm.webex.com/cirm/onstage/g.php?MTID=ef6aa60e45eb581e0e24ea4d2…
2. Click “Join Now”.

We will be providing a summary of the meeting’s highlights after the meeting—so stay tuned!

CIRM at Business of Personalized Medicine Summit

Exciting new technologies such as regenerative medicine, tissue engineering and gene therapy are already at the forefront of a new era of medicine. And today, CIRM’s own Business Development Officer, Neil Littman, moderated a panel titled The Impact of Next Generation Personalized Medicine Technologies: How Disruptive Tech Continues to Advance the Industry, at the annual Business of Personalized Medicine Summit.

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The panel discussed the innovative technologies we have at our disposal today, and provided a glimpse into the future—highlighting promising therapies already in the clinic as well as technologies that may be available in 5 to 10 years. For example, Curt Herberts, Senior Director of Corporate Development & Strategy from Sangamo BioSciences, discussed Sangamo’s grant under CIRM’s Strategic Partnership II Award, which uses genome-editing technology for a one-time treatment for the blood disorder Beta-thalassemia.

Importantly, the panel delved into potential paradigm shifts in medical care that may arise as a result of these new technologies, and discussed how to translate these cutting-edge technologies into human clinical trials. Carlos Olguin, Head of Bio/nano/Programmable Matter Group, Autodesk and Dr. Kumar Sharma, who directs the Center for Renal Translational Medicine University of California, San Diego La Jolla, rounded out the panel.

Finally, Neil asked panel members to discuss the issues surrounding market adoption and the potential resistance to paradigm-shifting technologies, the final hurdle in the delivery of much-needed therapies to patients.