Cranking it Up to Eleven: Heightened Growth of Neural Stem Cells Linked to Autism-like Behavior

Autism is not one single disease but a suite of many, which is why researchers have long struggled to understand its underlying causes. Often referred to as the Autism Spectrum Disorders, autism has been linked to multiple genetic and environmental factors—different combinations of which can all result in autism or autistic-like behavior.

Could an unusual boost in neural stem cell growth during pregnancy be linked to autistim-like behavior in children?

Could an unusual boost in neural stem cell growth during pregnancy be linked to autitism-like behavior in children?

But as we first reported in last week’s Weekly Roundup, scientists at the University of California, Los Angeles (UCLA) have identified a new factor that can occur during pregnancy and that may be linked to the development of autism-like behavior. These results shed new light on a notoriously murky condition.

UCLA scientist Dr. Harley Kornblum led the study, which was published last week in the journal Stem Cell Reports.

In it, Kornblum and his team describe how inflammation in pregnant mice, known as ‘maternal inflammation’ caused a spike in the production of neural stem cells—cells that one day develop into mature brain cells, such as neurons and glia cells. This abnormal growth, the team argues, led to enlarged brains in the newborn mice and, importantly, autism-like behavior such as decreased vocalization and social behavior, as well as overall increase in anxiety and repetitive behaviors, such as grooming. As Kornblum explained in a news release:

“We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals.”

However, Kornblum notes that many environmental factors may cause inflammation during pregnancy—and the inflammation itself is not thought to directly cause autism.

“Autism is a complex group of disorders, with a variety of causes. Our study shows a potential way that maternal inflammation could be one of those contributing factors, even if it is not solely responsible, through interactions with known risk factors.”

These known risk factors include genetic mutations, such as those to a gene called PTEN, which have been shown to increase one’s risk for autism.

Further research by Kornblum’s team further clarified the connection between inflammation and neural stem cell overgrowth. Specifically, they noticed a series of chemical reactions, known as a molecular pathway, appeared to stimulate the growth of neural stem cells in the developing mice. The identification of pathways such as these are vital when exploring new types of therapies—because once you know the pathway’s role in disease, you can then figure out how to change it.

“The discovery of these mechanisms has identified new therapeutic targets for common autism-associated risk factors,” said Dr. Janel Le Belle, the paper’s lead author. “The molecular pathways that are involved in these processes are ones that can be manipulated and possibly even reversed pharmacologically.”

These findings also support previous clinical findings that the roots of autism likely begin in the womb and continue to develop after birth.

One key difference between this work and previous studies, however, was that most studies point to irregularities in the way that neurons are connected as a key factor that leads to autism. This study points to not just a network ‘dysregulation,’ but also perhaps an overabundance of neurons overall.

“Our hypothesis—that one potential means by which autism may develop is through an overproduction of cells in the brain, which then results in altered connectivity—is a new way of thinking about autism.”

Advances in the fields of stem cell biology and regenerative medicine have given new hope to families caring for autistic loved ones. Read more about one such family in our Stories of Hope series. You can also learn more about how CIRM-funded researchers are building our understanding of autism in our recent video: Reversing Autism in the Lab with help from Stem Cells and the Tooth Fairy.

Stem cell stories that caught our eye: fast track marketing in Japan, a 3D cell tour and autism

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.

Event showed great progress, but Japan nipping at our heals. The San Diego Union Tribune’s Brad Fikes seemed to be enjoying covering the Stem Cell Meeting on the Mesa in his own backyard in La Jolla. He stayed for the full two days of the industry Partnering Forum and when we chatted he said he had more good material than he could use. I was certainly willing to second the sentiment of the opening paragraph of the story he wrote:

“More than ever before, stem cell therapies appear poised to transform medicine — potentially curing heart disease, diabetes and paralyzing injuries, among other ailments.”

But the last portion of his piece was a little unsettling. He noted the frequent discussion at the meeting of Japan’s new fast track path for marketing stem cell therapies. The CEO of Athersys, one of the leading companies in the field, announced at the meeting that his company would be taking their lead product to Japan first for marketing, not the U.S.

Turning cell biology into a 3-D game. The ability to track cells has become one of the most important limiting factors in stem cell biology. We need to know where cells go when they are transplanted in the body, but even before that, we have found that the interaction of cells with their environment often determines if stem cell offspring do their jobs and we need to track cells to understand this.

Now a team at Drexel University that includes an expert in computer software and hardware used in gaming has

Researchers at Drexel touring a group of cells using 3D glasses.

Researchers at Drexel touring a group of cells using 3D glasses.

provided the field with an invaluable tool. They can label various cells with distinctive markers and follow their movements. More important they can use an elaborate software program to integrate individual slices of a tissue into a 3D sample that researchers can “tour” while wearing 3D glasses.

Red Orbit quoted Andrew Cohen the leader of the computer development team:

“It’s like Photoshop for cell biologists. The software outlines cells and blood vessels, keeping track of them as they’re dividing and moving around one another. This provides a wealth of information on the patterns of cell shape, motion and division. Visualization of the 3-D microscopy data together with the analysis results is a key step to measure and ultimately understand what drives these cells.”

Cally Templea, a leading expert from the Neural Stem Cell Institute in Rensselaer, NY, was also quoted about the power of this new tool to help stem cell biologists understand how stem cells interact with their environment:

“LEVER 3-D is amazing, it opens new vistas for understanding the stem cell niche.”

Autism linked to stem cell burst (in mice). The accelerated brain growth seen right after birth in many people with autism spectrum disorder has been linked to a burst of nerve stem cell division triggered by inflammation. The study at the University of California, Los Angeles, could explain why inflammation during pregnancy, either due to an autoimmune reaction or an infection, has been shown to be a risk factor for the disorder.

Health Canal posted the press release from the university that quoted the senior author of a paper in the journal Stem Cell Reports, Harley Kornblum:

“We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals.”

The researchers gave pregnant mice a toxin found in bacteria and discovered that it triggered an excess production of nerve stem cells in their pups. This resulted in enlarged brains and behavior associated with autism, such as a reduced interest in interacting with other mice.

Little guy regrowing his head could help us. While a few species have the ability to regrow a severed body part, the tiny Hydractinia—commonly called snail fur—out does the rest in that it can regrow its head. BBC did a nice job of describing work at the University of Galway trying to explain how it accomplishes the feat and putting the work into perspective with other recent research findings.

After harvesting the creatures off the backs of hermit crabs the Galway team isolated embryonic stem cells from them, to which they attributed the ability to regrow something as complex as a head. The snail fur may be unique in that no other adult animal is believed to harbor embryonic stem cells. The researchers hope to use the tiny creature to learn how we might be able to turn on some ancestral regenerative capacity in humans.

Don Gibbons

Scientists Reach Yet Another Milestone towards Treating Type 1 Diabetes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Policy Matters: Stem Cells and the Public Interest

Guest Author Geoff Lomax is CIRM’s Senior Officer for Medical and Ethical Standards.

In the spirit of Stem Cell Awareness Day, Cell Stem Cell has compiled a “Public Interest” collection of articles covering ethical, legal, and social implications of stem cell research and made it freely available. The collection may be found here.

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The collection covers issues ranging from research involving human embryos to the use of stem cell therapies in patients. For those of you interested in a good primer on the history of stem cell controversies, Herbert Gottweis provides a detailed review of the federal policy debate in the United States. This debate has resulted in inconsistent policy and disrupted research. Gottweis uses this history to support his message that a “comprehensive, and proactive policy approach in this field beyond the quick legal fix” is needed for patients to ultimately benefit from the science.

What I found most interesting about this collection was the focus on stem cell treatments and “tourism.” A majority of the articles address the use of stem cells in patients. This focus is an indicator of how far the field has progressed. Stem cells clinical trials are now a reality and this results in two separated but related considerations. First, is how to make sure prospective patients are well informed should they participate in a clinical trial. Second, how to avoid stem cell “snake oil” where someone is pitching an unproven procedure. These issues are related by their solution that involves empowerment and education of patients and their support networks.

For example, in Stem Cell Tourism and Public Education: The Missing Elements, Master writes:

“It is important for the scientific, medical, ethics, and policy communities to continue to promote accurate patient and public information on stem cell research and tourism and to ensure that it is effectively disseminated to patients by working alongside patient advocacy groups.”

Master’s team found that groups committed to the advancement of good science, including patient advocates and researchers, often lacked basic information about clinical trials and other options for patients. This lack of information may contribute to patients being wooed by those pitching unproven procedures. Thus, the research community should continue to work with patients and advocacy organizations to identity options for treatment.

Another aspect of patient empowerment is what Insoo Huyn refers to as “therapeutic hope” in his piece: Therapeutic Hope, Spiritual Distress, and the Problem of Stem Cell Tourism. Huyn suggests that a supportive system for delivering cell therapies should includes nurturing hope. He writes, “patients might understand when an intervention’s chances of success are extremely remote at best, but may still want to ‘‘give it a shot’’ as long as a beneficial outcome cannot be ruled out as categorically impossible.” Huyn recognizes that well developed early-stage clinical trials are not expected to provide a benefit to patients (they are designed to evaluate safety), but the nature of the therapeutic (often cells) means there may be some real effect.

A third piece by the ISSCR Ethics Taskforce titled Patients Beware: Commercialized Stem Cell Treatments on the Web presents a guide to evaluating therapies. They present five principles that patients, researchers and advocates can rally around to identify credible interventions. The taskforce states:

The guiding principles for the development of the recommended process were that (1) the standards for identifying and reviewing clinics and suppliers should be objective and clear; (2) the inquiry and review process should be publicly transparent and relatively straight- forward for any clinic or practitioner to comply with; (3) conflicts of interest, if any, of the declarant ought to be disclosed to the ISSCR; (4) there should be no actual or apparent conflicts of interest of staff or others involved in the inquiry or review process for any particular matter; and (5) any findings that a clinic fails to meet standards should be communicated in a specific factual way, rather than with broad conclusions of fraudulent practices.

While the Cell Stem Cell Public Interest series covers a range of issues related to stem cells and society, the emphasis on treatments and patients is a reminder of how far the field has come. There is broad consensus that patients, researchers and advocates have roles to play in advancing safe and effective cell therapies.

Geoff Lomax

Stem Cell Awareness Day and the Stem Cell Person of the Year

Today is Stem Cell Awareness Day, an event that seeks to bring together individuals and organizations around the world working to celebrate and raise awareness about the tremendous progress being made in stem cell research, and to ensure we remain focused on keeping that progress going until we have cures or treatments for people in need.

Paul Knoepfler

Paul Knoepfler

Today is also the day that our colleague, U.C. Davis stem cell researcher and avid blogger, Paul Knoepfler reveals the nominations for his annual Stem Cell Person of the Year award. It’s perfect timing, because many of those nominated have been pivotal in helping move the research forward, and in helping raise awareness about the field in general.

The rules for the competition are pretty simple. In Paul’s own words: “Who has been the single most important, influential person in the world of stem cells this year? Who has made the biggest positive contribution in 2014?”

This is the third year of the competition and Paul is not just a tireless champion of stem cell research, he’s also someone who puts his money where his mouth is. The prize for this year’s winner is $2,000, double that of the previous two years, and all that cash comes out of Paul’s own pocket. It’s a generous gesture from a tireless advocate. In fact those two qualities alone would suggest Paul qualifies to win his own competition. But he has too much integrity to ever even consider that.

So without further ado here is the list of nominations with quotes from some of the people who nominated them in green.

*Spoiler alert: a couple of those nominated are colleagues of mine here at the stem cell agency. I didn’t nominate them, but I can certainly testify to the fact that they deserve it.

Bernie Siegel – a long-time stem cell advocate who runs the yearly World Stem Cell Summit. “Has any one single person done more for the stem cell field?”

Chris Fasano: A principal investigator at the Neural Stem Cell Institute where he uses stem cells to study early nervous system development. Chris stands out for his energy, enthusiasm, dedication to the field, creativity and accomplishments.”

Diana DeGette, the Democratic Congresswoman from Colorado: a politician who has been working to pass important stem cell legislation. “Long time supporter of legislation to support stem cell research and regenerative medicine.”

Don Reed: long-time stem cell research advocate who played a key role in the success of Prop 71 and the creation of CIRM. “A tireless stem cell advocate always there to make a positive difference.”

Emmanuel (Ed) Baetge: Head of Nestlé Institute of Health Sciences at Nestlé Health Science and formerly CSO of Novocell/ViaCyte. “Ed was the driving force behind the development of Novocell (Viacyte’s) diabetes program using hESCs to develop a cell therapy for T1/2 patients…the phase 1 trial is enrolling this year. It has huge potential and Ed deserves the credit for his leadership and development of the technology as well as the company.”

Ellen Feigal; Vice President, Research and Development at the California Institute for Regenerative Medicine (CIRM). “At CIRM Dr. Feigal makes the Development Program happen.”

Ian mcNiece: Professor, Department of Stem Cell Transplantation,
Division of Cancer Medicine, The University of Texas MD Anderson
Cancer Center.

Janet Rossant: Senior Scientist in the Developmental & Stem Cell Biology Program and Chief of Research at The Hospital for Sick Children, Toronto

Jeanne Loring: Stem cell researcher and scholar, leading iPS cell clinical work in the pipeline for Parkinson’s Disease, and patient advocate. “Supportive to the advocacy community. Courage in supporting the challenge to WARF patents. Excellent scientist engaged in policy discussions.”

John Sinden: The co-founder of ReNeuron, a biotech company based in UK. “Thanks to his determination, and drive ReNeuron has a clinical approved stem cell product currently tested in two clinical trials.”

Judy Roberson: Long-time Huntington’s Disease patient advocate. “She makes concrete positive developments happen such as millions of dollars in research funding for HD.”

Leigh Turner: Outspoken advocate of evidence-based medicine in the stem cell field. “Gave an inspiringly frank talk about for-profit stem cell clinics flouting FDA regulations at ISSCR 2014.”

Malin Parmer: Associate Professor, Developmental and Regenerative Neurobiology, Lund University. Top neural regeneration scientist. “Young, hard worker who is doing very well”.

Masayo Takahashi: Stem cell researcher leading the team that is doing the first ever clinical study based on human iPS cells. “Creative and courageous clinical stem cell researcher.”

Mike West: He founded Geron and was CSO of Advanced Cell Technology before his current position as head of BioTime. “He has been a leader in our regen field for many years but he made a bold decision to resurrect Geron’s cell therapy for spinal cord injury this year and hopefully confirm the promise of hESC technology clinically.”

Patricia Olson: Executive Director of Scientific Activities at CIRM and active in CIRM scientific leadership from day 1. “A driving force in the stem cell field.”

Peter Zandstra: Professor at University of Toronto. Stem cell researcher. Canada Research Chair of Stem Cell Bioengineering. “Peter is a recognized pioneer and respected world leader at bringing concepts of scale-up, regulation, and industrialization to stem cell-derived cell therapy technologies.”

Pope Francis: Leader of Worldwide Catholic Church. “Strong supporter of adult stem cell biotechs and research”.

Richard Cohen: An MS patient in a clinical trial who has chronicled his experiences. An author and Meredith Vieira’s husband, father of three children. “Mr. Cohen is an inspiration to me and others because he’s very honest and doesn’t sugar-coat his struggles, losses, frustrations, anger, embarrassments, and he also shares his gains.”

Richard Garr: CEO of Neuralstem, conducting work on using stem cells for ALS and advocate of Right To Try laws. “Richard does two excellent things at once: making a treatment for ALS and connecting with ALS patients.”

Robert Lanza: CEO of Advanced Cell Technology, which has multiple ES cell-based clinical trials ongoing. “Visionary and practical so makes the impossible possible”.

Shoukhrat Mitalipov: Stem cell researcher who first successfully made nuclear transfer human ES cells by therapeutic cloning and developing oocyte transfer-based therapies for mitochondrial disorders. “Gutsy pioneer of new, game changing technologies.”

Susan Solomon: Co-Founder and CEO of The New York Stem Cell Foundation (NYSCF). Remarkably effective advocate for stem cell research. “not many leaders have created their own research laboratories and raised $100 million plus. Seriously, what an accomplishment!”

Takaho Endo: Senior Researcher at the Riken Center for Integrative Medical Sciences in Yokohama who published key genetic work on the possible origin of STAP cells. “Courage to publish this being from RIKEN.”

Ted Harada: Leading stem cell research advocate and very effective ALS patient advocate. “An Energizer Bunny for the ALS community and stem cell advocate”

Tory Williams: Stem cell advocate and author of the 2014 book, Inevitable Collision. Co-Founder and Executive Director of the Alabama Institute of Medicine (AIM). “A true hero who inspires and makes concrete things happen like AIM”.

These Are the Cells You’re Looking for: Scientists Devise New Way to Extract Bone-Making Stem Cells from Fat

Buried within our fat tissue are stashes of stem cells—a hidden reservoir of cells that, if given the right cues, can transform into cells that make up bone, cartilage or fat. These cells therefore represent a much-needed store for regenerative therapies that rebuild bone or cartilage lost to disease or injury.

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). [Credit: Darling lab/Brown University]

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). The center image shows both types of cells prior to sorting [Credit: Darling lab/Brown University]

The only problem with these tucked-away cellular reservoirs, however, is identifying them and getting them out.

But now, researchers at Brown University have devised a unique method of identifying, extracting and then cultivating these bone-producing stem cells. Their results, published today in the journal Stem Cell Research & Therapy, seem to offer a much-needed alternative resource for growing bone.

Traditional methods attempting to locate and extract these stem cells focused on proteins that reside on the surface of the cells. Find the proteins, scientists reasoned, and you’ve found the cell.

Unfortunately, that method was not fool proof, and many argued that it wasn’t finding all the cells that reside in the fat tissue. So Brown scientists, led by Dr. Eric Darling found an alternative.

They knew that a gene called ALPL is an indicator of bone-making cells. If the gene is switched on, the cell has the potential to make bone. If it’s switched off, it does not. So Darling and his team devised a fluorescent marker, or tag, that stuck to the cells with activated ALPL. They then used a special machine to sort the cells: those that glowed went into one bucket, those that did not went into the other.

To prove that these ALPL-activated cells were indeed capable of becoming bone and cartilage, they then cultivated them for several weeks in a petri dish. Not only did they transform into the right cell types—they did so in greater numbers than cells extracted using traditional methods.

Hetal Marble, a graduate student in Darling’s lab and the paper’s first author, argues that tagging genes—rather than surface proteins—in order to distinguish and weed out cell types represents an important paradigm shift in the field. As he stated in a press release:

“Approaches like this allow us to isolate all the cells that are capable of doing what we want, whether they fit the archetype of what a stem cell is or is not. The paradigm shift is thinking about isolating populations that are able to achieve an end point rather than isolating populations that fit a strictly defined archetype.”

While their method is both precise and accurate, there is one drawback: it is slow.

Currently, it takes four days to tag, extract and cultivate the bone-making cells. In the future, the team hopes they can shorten this time frame so that they could perform the required steps within a single surgical session. As Darling stated:

“If you can take a patient into the OR, isolate a bunch of their cells, sort them and put them back in—that’s ideally where we’d like to go with this.”

Stem cell stories that caught our eye: heart disease, blindness and replacement teeth

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.

Review looks at approaches to blindness.
The Scientist published a nice lay level overview of various teams’ work to use stem cells to cure blindness. The bulk of the story covers age-related macular degeneration, the most common form of blindness in the elderly, with six approaches discussed and compared including the CIRM-funded California Project to Cure Blindness.

Dennis Clegg, one member of the California project team, was featured in a story posted by his university

The piece smartly includes an overview of the reasons eye diseases make up a disproportionate number of early stem cell trials using stem cells from sources other than bone marrow. Many in the field view it as the perfect target for early therapies where safety will be a main concern. It is a confined space so the cells are less likely to roam; it is small so fewer cells will be needed; and it has reduced immune activity so less likely to reject new cells.

The author describes three approaches to using cells derived from embryonic stem cells, one using iPS-type stem cells, one using fetal-derived nerve stem cells and one using cells from umbilical cord blood. An ophthalmologist from the University of Wisconsin who was not associated with any of the trials offered a fair assessment:

“We’re pushing the boundaries of this technology. And as such, we expect there to be probably more bumps in the road than smooth parts.”


A heart of gold, nanoparticles that is.
Most teams using scaffolds seeded with cells to create patches to strengthen damaged hearts start with animal material to create the scaffold, which can cause immune problems. An Israeli group has developed a way to use a patient’s own fat tissue to create these scaffolds. But that left the remaining problem of getting cells in a scaffold to beat in unison with the native heart. They found that by lacing the scaffold with gold nanoparticles they could create an effective conduction system for the heart’s electrical signals.

A story in ScienceDaily quotes the lead researcher Tal Dvir:

“The result was that the nonimmunogenic hybrid patch contracted nicely due to the nanoparticles, transferring electrical signals much faster and more efficiently than non-modified scaffolds.”

If you read the story parts of it are a little overwrought. The headline, “A Heartbeat away? Hybrid patch could replace transplants,” pushes credibility on two fronts. The first half suggests this therapy is imminent, rather than the reality of years away. Patches could only replace the need for transplants. They could never work as well as a full new heart, but since we only need partial function in our heart to live relatively OK, and they might be safer than a transplant they might replace the need.

Could teeth be first complex organ stem cell success? The Seattle Times did a pretty thorough story about why the tooth might be the first complex organ replaced via stem cells and regenerative medicine. While it is a complex organ with multiple layers, a blood system and a nervous system, it does not have moveable parts and we understand each part better than with other major organs.

The paper starts with a good reminder of just how far dental hygiene has come, with few elderly people needing dentures today—leaving the need for new teeth, suggests the author, to people such as hockey players.

A CIRM-funded team is investigating various ways to build a new tooth.

Even the Tea Party would like this regulation.
We have roughly as many genes as a frog, but are much more complicated. Our higher function evolved in part by making our genes more highly regulated. A CIRM-funded team now reports that this particularly applies to our “jumping genes,” and no that does not have anything to do with jumping frogs.

The work focuses on transposons, bits of our DNA that literally move around, or jump, between our functional genes and change how they are turned on or off. We also have evolved a set of genes to control the jumping genes, and the researchers at the University of California, Santa Cruz, suggest that evolution has been a never ending tug of war between the jumping genes and the genes that are supposed to control them.

HealthCanal ran the university’s press release, which quotes lead researcher Sofie Salama:

“We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about.”

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/