CIRM-Funded Clinical Trials Targeting Brain and Eye Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

 This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Our Agency has funded a total of 40 trials since its inception. 23 of these trials were funded after the launch of our Strategic Plan in 2016, bringing us close to the half way point of our goal to fund 50 new clinical trials by 2020.

Today we are featuring CIRM-funded trials in our neurological and eye disorders portfolio.  CIRM has funded a total of nine trials targeting these disease areas, and seven of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

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CIRM Bridges Student Researcher Discovers Mentoring is a Two-Way Street

Jasmine Carter is a CIRM Bridges Scholar a Sacramento State University. She currently is interning in the lab of Dr. Kyle Fink at UC Davis and her research focuses on developing induced neurons from skin cells to model neurological disorders and develop novel therapeutics. Jasmine was a mentor to one of our UC Davis CIRM SPARK high school students this summer, and we asked her to share her thoughts on the importance of mentorship in science.

I began my scientific journey as an undergraduate student in the biomedical sciences, determined to get into medical school to become a surgeon. But I was perpetually stressed, always pushing towards the next goal and never stopping to smell the roses. Until one day, I did stop because a mentor encouraged me to figure out how I wanted to contribute to the medical field. In the midst of contemplating this important question, I was offered an undergraduate research position studying stem cells. It wasn’t long before I realized I had found my calling. Those little stem cells were incredibly fascinating to me, and I really enjoyed my time in a research lab. Being able to apply my scientific knowledge at the lab bench and challenge myself to solve biological problems was truly enjoyable to me so I applied to and was accepted into Sacramento State’s CIRM Bridges Program.

Jasmine working with stem cells in the cell culture hood.

To say I was excited to learn more about stem cell biology would be an understatement. I started volunteering in the Translational Research Lab at the Institute for Regenerative Cures at UC Davis as soon as I could. And I started to feel way outside my comfort zone as I walked into the lab because the seemingly endless rows of research benches and all the lab equipment can be a lot to take in when you first begin your research journey. When I started to actually run experiments, I worried that I may have messed the experiment up. I worried that I might SAY or DO something that would make me appear less intelligent because everyone was so knowledgeable. I struggled with figuring out whether or not I was cut out for the research environment.

I have now started my formal research internship and am constantly amazed at the mentorship I receive and collaboration I witness every day; everyone is always willing to lend a helping hand or simply be a sounding board for ideas. I have learned an immense amount of knowledge about stem cell research and its potential to improve knowledge for the scientific community and treatment options for patients. But I would not have had the opportunity to grow as an intern and learn from experts in various disciplines if it were not for the CIRM Bridges Program. The Bridges Program has allowed me to apply basic biological principles as I learn about stem cell biology and the applications of stems cells while completing a Master’s research project. Diving into the research environment has been challenging at times, but guidance from knowledgeable and encouraging mentors in the Translational Research Laboratory has helped to shape me into a more confident researcher.

Jasmine and Yasmine.

As fate would have it, just as I was becoming more and more confident in myself as a researcher, I found myself becoming a mentor to our CIRM SPARK high school intern, Yasmine. During Yasmine’s first week, I saw the exact same feelings of doubt on her face that I had experienced when I first volunteered in the laboratory. I saw how she challenged herself to absorb and understand every word and concept we said to her. I saw that familiar worried expression she’d displayed when unsure if she just messed up on an experiment or the hesitation when trying to figure out if the question she was about to ask was the “right” one. Because I had faced the same struggles, I could assure her that the internship was a learning experience and that each success and setback she encountered while working on her project would make her a better scientist.

During Yasmine’s eight-week summer internship, she observed and helped members of our team on various experiments while conducting her own research project. At the end of the first week, Yasmine commented on how diligent all the researchers in the lab were; how she hadn’t known the amount of effort and work that’s required to develop and complete a research project. Yasmine’s project focused on optimizing the protocols, or recipes, for editing genes in different types of cells for use as potential treatments for neurological disorders. Many days, you’d find Yasmine peering into the microscope and imaging cells – for her project or one of ours. Being able to visually assess the success of our experiments was exciting for her. The time we spent trying to track down just one fluorescent cell was a great opportunity for us to review the experiment and brainstorm the next set of experiments we wanted to run. I enjoyed explaining the science behind the experiments we set up, and Yasmine’s thought provoking questions sometimes led to a learning session where we figured out the answer together. Yasmine even used the knowledge she was acquiring in a graduate level Good Manufacturing Practice (GMP) course to explain her flow cytometry results to our team during a lab meeting.

Yasmine at the microscope.

It was actually during one of these lab meetings when I was practicing my poster presentation for the 2017 Annual CIRM Bridges Trainee Meeting when Yasmine said, “I finally understand your project”. She and I had frequently discussed my project, but towards the end of the internship she was integrating what she learned in lectures, whiteboard review sessions and scientific papers to the research we were doing at the lab bench. It was incredibly gratifying to see how much she had learned and how her confidence as a young scientist grew while she interned with us. The internship was an invaluable experience for Yasmine because it helped to reinforce her commitment to improving the lives of patients who suffer from brain cancer. She hopes to use the research skills that the SPARK program provided to seek out research opportunities in college.

But the learning wasn’t one-sided this summer because I was also learning from Yasmine. The CIRM SPARK students are encouraged to document their internship on social media. And with Yasmine’s encouragement, I have started to document my experiences in the Bridges program by showing what the day to day life of a graduate student looks like, what experiments are going well and how I am trouble-shooting the failed experiments. Sometimes those failed experiments can be discouraging, but taking the time to discuss it with a mentor, mentee or an individual on social media can help me to figure out how I should change the experiment. So, when self-doubt sprouted back up as I began to document my experiences in the program, I reminded myself that being pushed outside my comfort zone is a great way to learn. But one of the greatest lessons I learned from Yasmine’s summer internship is the importance of sharing in a mentor-mentee relationship. After sharing my knowledge with Yasmine, I got to watch her confidence shine when she took the reins with experiments and then shared the fruits of her labor with me.

There can be a lot of ups and downs in research. However, opportunities for mentorship and learning with such bright, enthusiastic and dedicated students has certainly validated the importance of the CIRM Bridges and SPARK programs. The mentorship and collaboration that occurs between high school interns, undergraduates, graduate students, post-docs and principal investigators to develop therapies for patients with unmet medical needs is truly amazing.

Mentorship leads to productive careers and friendships.

Jasmine Carter is also an avid science communicator. You can follow her science journey on Instagram and Twitter.

Blocking spike in stem cell growth after brain injury may lessen memory decline, seizures

Survivors of traumatic brain injury (TBI) often suffer from debilitating, life changing symptoms like memory decline and epileptic seizures. Researchers had observed that following TBI, a stem cell-rich area of the brain provides a spike in new nerve cell growth, presumably to help replace damaged or destroyed brain cells. But, like a lot of things in biology, more is not always better. And a new report in Stem Cell Reports provides evidence that this spark of brain cell growth shortly after TBI may actually be responsible for post-injury seizures as well as long-term memory problems for people with this condition.The Rutgers University research team behind the study came to this counterintuitive conclusion by examining brain injury in laboratory rats. They showed that brain cells at the injury site that are known to play a role in memory had doubled in number within three days after injury. But a month later, these brain cells had decreased by more than half the amount seen in rats without injury. Neural stem cells, which develop into the mature cells found in the brain, showed this same up and down pattern, suggesting they were responsible for the loss of the brain cells. Lead scientist, professor Viji Santhakumar, described how these changes in brain cell growth lead to brain injury symptoms:

“There is an initial increase in birth of new neurons after a brain injury but within weeks, there is a dramatic decrease in the normal rate at which neurons are born, depleting brain cells that under normal circumstances should be there to replace damaged cells and repair the brain’s network,” she said in a press release. “The excess new neurons lead to epileptic seizures and could contribute to cognitive decline. It is normal for the birth of new neurons to decline as we age. But what we found in our study was that after a head injury the decline seems to be more rapid.”

The researchers next aimed to slow down this increase in nerve cell growth after injury. To accomplish this goal, they used an anti-cancer drug currently in clinical trials which has been known to block the growth and survival of new nerve cells. Sure enough, the drug blocked this initial, rapid burst in nerve cells in the rats, which prevented the long-term decline in the brain cells that are involved in memory decline. The team also reported that the rats were less vulnerable to seizures when this drug was administered.

“That’s why we believe that limiting this process might be beneficial to stopping seizures after brain injury,” Dr. Santhakumar commented.

Hopefully, these findings will one day help lessen these short- and long-term, life-altering symptoms seen after brain injury.

Hearts and brains are center stage at CIRM Patient Advocate event

Describing the work of a government agency is not the most exciting of topics. Books on the subject would probably be found in the “Self-help for Insomniacs” section of a good bookstore (there are still some around). But at CIRM we are fortunate. When we talk about what we do, we don’t talk about the mechanics of our work, we talk about our mission: accelerating stem cell therapies to people with unmet medical needs.

Yesterday at the Gladstone Institutes in San Francisco we did just that, talking about the progress being made in stem cell research to an audience of friends, supporters and patient advocates. We had a lot to talk about, including the 35 clinical trials we have funded so far, and our goals and hopes for the future.

We were lucky to have Dr. Deepak Srivastava and Dr. Steve Finkbeiner from Gladstone join us to talk about their work. Some people are good scientists, some are good communicators. Deepak and Steve are great scientists and equally great communicators.

Deepak Srivastava highlighted ongoing stem cell research at the Gladstone
(Photo: Todd Dubnicoff/CIRM)

Deepak is the Director of the Roddenberry Stem Cell Center at Gladstone (and yes, it’s named after Gene Roddenberry of Star Trek fame) and an expert on heart disease. He talked about how advances in research have enabled us to turn heart scar tissue cells into new heart muscle cells, creating the potential to use a person’s own cells to help them recover from a heart attack.

“If you have a heart attack, your heart turns that muscle into scar tissue which affects the heart’s ability to pump blood around the body. We identified a combination of factors that support cells that are already in your heart and we have found a way of converting those scar cells into muscle. This could help repair the heart enough so you may not need a transplant, but you can lead a much more normal life.”

He said this research is now advancing to the point where they hope it could be ready for testing in people in the not too distant future and joked that his father, who has had a heart attack, volunteered to be the second person to try it. “Not the first but definitely the second.”

Steve, who is the Director of the Taube/Koret Center for Neurodegenerative Disease Research, specializes in problems in the brain; everything from Alzheimer’s and Parkinson’s to schizophrenia and ALS (also known as Lou Gehrig’s disease.

He talked about his uncle, who has end stage Parkinson’s disease, and how he sees first-hand how devastating this neurodegenerative disease is, and how that personal connection helps motivate him to work ever harder.

He talked about how so many therapies that look promising in mice fail when they are tested in people:

“A huge motivation for me has been to try and figure out a more reliable way to test these potential therapies and to move discoveries from the lab and into clinical trials in patients.”

Steve is using ordinary skin cells or tissue samples, taken from people with Parkinson’s and Alzheimer’s and other neurological conditions, and using the iPSC technique developed by Shinya Yamanaka (who is a researcher at Gladstone and also Director of CIRA in Japan) turns them into the kinds of cells found in the brain. These cells then enable him to study how these different diseases affect the brain, and come up with ways that might stop their progress.

Steve Finkbeiner is using human stem cells to model brain diseases
(Photo: Todd Dubnicoff/CIRM)

He uses a robotic microscope – developed at Gladstone – that allows his team to study these cells and test different potential therapies 24 hours a day, seven days a week. This round-the-clock approach will hopefully help speed up his ability to find something that help patients.

The CIRM speakers – Dr. Maria Millan, our interim President and CEO – and Sen. Art Torres (ret.) the Vice Chair of our Board and a patient advocate for colorectal cancer – talked about the progress we are making in helping push stem cell research forward.

Dr. Millan focused on our clinical trial work and how our goal is to create a pipeline of promising projects from the work being done by researchers like Deepak and Steve, and move those out of the lab and into clinical trials in people as quickly as possible.

Sen. Art Torres (Ret.)
(Photo: Todd Dubnicoff/CIRM)

Sen. Torres focused on the role of the patient advocate at CIRM and how they help shape and influence everything we do, from the Board’s deciding what projects to support and fund, to our creating Clinical Advisory Panels which involve a patient advocate helping guide clinical trial teams.

The event is one of a series that we hold around the state every year, reporting back to our friends and supporters on the progress being made. We feel, as a state agency, that we owe it to the people of California to let them know how their money is being spent.

We are holding two more of these events in the near future, one at UC Davis in Sacramento on October 10th, and one at Cedars-Sinai Medical Center in Los Angeles on October 30th.

CIRM weekly stem cell roundup: minibrain model of childhood disease; new immune insights; patient throws out 1st pitch

New human Mini-brain model of devastating childhood disease.
The eradication of Aicardi-Goutieres Syndrome (AGS) can’t come soon enough. This rare but terrible inherited disease causes the immune system to attack the brain. The condition leads to microcephaly (an abnormal small head and brain size), muscle spasms, vision problems and joint stiffness during infancy. Death or a persistent comatose state is common by early childhood. There is no cure.

Though animal models that mimic AGS symptoms are helpful, they don’t reflect the human disease closely enough to provide researchers with a deeper understanding of the mechanisms of the disease. But CIRM-funded research published this week may be a game changer for opening up new therapeutic strategies for the children and their families that are suffering from AGS.

Organoid mini-brains are clusters of cultured cells self-organized into miniature replicas of organs. Image courtesy of Cleber A. Trujillo, UC San Diego.

To get a clearer human picture of the disease, Dr. Alysson Muotri of UC San Diego and his team generated AGS patient-derived induced pluripotent stem cells (iPSCs). These iPSCs were then grown into “mini-brains” in a lab dish. As described in Cell Stem Cell, their examination of the mini-brains revealed an excess of chromosomal DNA in the cells. This abnormal build up causes various toxic effects on the nerve cells in the mini-brains which, according to Muotri, had the hallmarks of AGS in patients:

“These models seemed to mirror the development and progression of AGS in a developing fetus,” said Muotri in a press release. “It was cell death and reduction when neural development should be rising.”

In turns out that the excess DNA wasn’t just a bunch of random sequences but instead most came from so-called LINE1 (L1) retroelements. These repetitive DNA sequences can “jump” in and out of DNA chromosomes and are thought to be remnants of ancient viruses in the human genome. And it turns out the cell death in the mini-brains was caused by the immune system’s anti-viral response to these L1 retroelements. First author Charles Thomas explained why researchers may have missed this in their mouse models:

“We uncovered a novel and fundamental mechanism, where chronic response to L1 elements can negatively impact human neurodevelopment. This mechanism seems human-specific. We don’t see this in the mouse.”

The team went on to test the anti-retroviral effects of HIV drugs on their AGS models. Sure enough, the drugs decreased the amount of L1 DNA and cell growth rebounded in the mini-brains. The beauty of using already approved drugs is that the route to clinical trials is much faster and in fact a European trial is currently underway.

For more details, watch this video interview with Dr. Muotri:

New findings about immune cell development may open door to new cancer treatments
For those of you who suffer with seasonal allergies, you can blame your sniffling and sneezing on an overreaction by mast cells. These white blood cells help jump start the immune system by releasing histamines which makes blood vessels leaky allowing other immune cells to join the battle to fight disease or infection. Certain harmless allergens like pollen are mistaken as dangerous and can also cause histamine release which triggers tearing and sneezing.

Mast cells in lab dish. Image: Wikipedia.

Dysfunction of mast cells are also involved in some blood cancers. And up until now, it was thought a protein called stem cell factor played the key role in the development of blood stem cells into mast cells. But research reported this week by researchers at Karolinska Institute and Uppsala University found cracks in that previous hypothesis. Their findings published in Blood could open the door to new cancer therapies.

The researchers examine the effects of the anticancer drug Glivec – which blocks the function of stem cell factor – on mast cells in patients with a form of leukemia. Although the number of mature mast cells were reduced by the drug, the number of progenitor mast cells were not. The progenitors are akin to teenagers in that they’re at an intermediate stage of development, more specialized than stem cells but not quite mast cells. The team went on to confirm that stem cell factor was not required for the mast cell progenitors to survive, multiply and mature. Instead, their work identified two other growth factors, interleukin 3 and 6, as important for mast cell development.

In a press release, lead author Joakim Dahlin, explained how these new insights could lead to new therapies:

“The study increases our understanding of how mast cells are formed and could be important in the development of new therapies, for example for mastocytosis for which treatment with imatinib/Glivec is not effective. One hypothesis that we will now test is whether interleukin 3 can be a new target in the treatment of mast cell-driven diseases.”

Patient in CIRM-funded trial regains use of arms, hands and fingers will throw 1st pitch in MLB game.
We end this week with some heart-warming news from Asterias Biotherapeutics. You avid Stem Cellar readers will remember our story about Lucas Lindner several weeks back. Lucas was paralyzed from the neck down after a terrible car accident. Shortly after the accident, in June of 2016, he enrolled in Asterias’ CIRM-funded trial testing an embryonic stem cell-based therapy to treat his injury. And this Sunday, August 13th, we’re excited to report that due to regaining the use of his arms, hands and fingers since the treatment, he will throw out the first pitch of a Major League Baseball game in Milwaukee. Congrats to Lucas!

For more about Lucas’ story, watch this video produced by Asterias Biotherapeutics:

Making brain stem cells act more like salmon than bloodhounds

Like salmon swimming against a river current, brain stem cells can travel against their normal migration stream with the help of electrical stimuli, so says CIRM-funded research published this week in Stem Cell Reports. The research, carried out by a team of UC Davis scientists, could one day provide a means for guiding brain stem cells, or neural stem cells (NSCs), to sites of disease or injury in the brain.

Min_SCR full

Human neural stem cells (green) guided by electrical stimulation migrated to and colonized the subventricular zone of rats’ brains. This image was taken three weeks after stimulation. Image: Jun-Feng Feng/UC DAVIS, Sacramento and Ren Ji Hospital, Shanghai.

NSCs are a key ingredient in the development of therapies that aim to repair damaged areas of the brain. Given the incredibly intricate structure of nerve connections, targeting these stem cells to their intended location is a big challenge for therapy development. One obstacle is mobility. Although resident NSCs can travel long distances within the brain, the navigation abilities of transplanted NSCs gets disrupted and becomes very limited.

In earlier work, the research team had shown that electrical currents could nudge NSCs to move in a petri dish (watch team lead Dr. Min Zhao describe this earlier work in the 30 second video below) so they wanted to see if this technique was possible within the brains of living rats. By nature, NSCs are more like bloodhounds than salmon, moving from one location to another by sensing an increasing gradient of chemicals within the brain. In this study, the researchers transplanted human NSCs in the middle of such a such gradient, called the rostral migration stream, that normally guides the cells to the olfactory bulb, the area responsible for our sense of smell.

Electrodes were implanted into the brains of the rats and an electrical current flowing in the opposite direction of the rostral migration stream was applied. This stimulus caused the NSCs to march in the direction of the electrical current. Even at three and four weeks after the stimulation, the altered movement of the NSCs continued. And there was indication that the cells were specializing into various types of brain cells, an important observation for any cell therapy meant to replace diseased cells.

The Scientist interviewed Dr. Alan Trounson, of the Hudson Institute of Australia, who was not involved in study, to get his take on the results:

“This is the first study I’ve seen where stimulation is done with electrodes in the brain and has been convincing about changing the natural flow of cells so they move in the opposite direction. The technique has strong possibilities for applications because the team has shown you can move cells, and you could potentially move them into seriously affected brain areas.”

Though it’s an intriguing proof-of-concept, much works remains to show this technique is plausible in the clinic. Toward that goal, the team has plans to repeat the studies in primates using a less invasive method that transmits the electrical signals through the skull.

Scientist grow diseased brain cells in bulk to study Alzheimer’s and Parkinson’s disease

Daily trips to the local grocery store have become a thing of the past for many with the rise of wholesale stores like Costco and online giants like Amazon. Buying in bulk is attractive for people who lead busy lives, have large families, or just love having endless pairs of clean socks.

Scientists who study neurodegenerative diseases like Alzheimer’s and Parkinson’s use disease-in-a-dish models that are much like the daily visits to the nearby Safeway. They can make diseased brain cells, or neurons, from human pluripotent stem cells and study them in the lab. But often, they can’t generate large enough quantities of cells to do important experiments like test new drugs or develop diagnostic platforms to identify disease at an earlier age.

What scientists need is a Costco for brain cells, a source that can make diseased brain cells in bulk. Such a method would open a new avenue of research into what causes neurodegeneration and how the aging process affects its progression.

This week, this need was answered. A team of researchers from Lund University in Sweden developed a method that can efficiently generate neurons from patients with a range of neurodegenerative diseases including Parkinson’s, Huntington’s and Alzheimer’s disease. The study was published in EMBO Molecular Medicine and was led by senior author Dr. Malin Parmar.

Diseased neurons made by the Lund University team. (Photo, Kennet Ruona)

Parmar and her team took an alternative approach to making their neurons. Their technology involves converting human skin cells into neurons without reprogramming the skin cells back to a pluripotent stem cell state first. This process is called “direct conversion” and is considered an effective shortcut for generating mature cells like neurons in a dish. Direct conversion of skin cells into neurons was first published by Dr. Marius Wernig, a CIRM-grantee and professor at Stanford University.

There is also scientific evidence suggesting that reprogramming patient cells back to a pluripotent state wipes out the effects of aging in those cells and has a Benjamin Button-like effect on the resulting neurons. By directly converting patient skin cells into neurons, many of these aging “signatures” are retained and the resulting neurons are more representative of the aging brain.

So how did they make brain cells in bulk? Parmar explained their method in a Lund University news release,

Malin Parmar

“Primarily, we inhibited a protein, REST, involved in establishing identity in cells that are not nerve cells. After limiting this protein’s impact in the cells during the conversion process, we’ve seen completely different results.”

 

Besides blocking REST, the team also turned on the production of two proteins, Ascl1 and Brn2, that are important for the development of neurons. This combination of activating pro-neural genes and silencing anti-neural genes was successful at converting skin cells into neurons on a large scale. Parmar further explained,

“We’ve been playing around with changing the dosage of the other components in the previous method, which also proved effective. Overall, the efficiency is remarkable. We can now generate almost unlimited amounts of neurons from one skin biopsy.”

As mentioned previously, this technology is valuable because it provides better brain disease models for scientists to study and to screen for new drugs that could treat or delay disease onset. Additionally, scientists can study the effects of the aging in the brain at different stages of neurodegeneration. Aging is a well-known risk factor for many neurodegenerative diseases, especially Alzheimer’s, so the ability to make large quantities of brain cells from elderly Alzheimer’s patients will unlock new clues into how age influences disease.

Co-author Dr. Johan Jakobsson concluded,

Johan Jakobsson

“This takes us one step closer to reality, as we can now look inside the human neurons and see what goes on inside the cell in these diseases. If all goes well, this could fundamentally change the field of research, as it helps us better understand the real mechanisms of the disease. We believe that many laboratories around the world would like to start testing on these cells to get closer to the diseases.”

For more on this study, check out this short video provided by Lund University.

Stories that caught our eye: An antibody that could make stem cell research safer; scientists prepare for clinical trial for Parkinson’s disease; and the stem cell scientist running for Congress

Antibody to make stem cells safer:

There is an old Chinese proverb that states: ‘What seems like a blessing could be a curse’. In some ways that proverb could apply to stem cells. For example, pluripotent stem cells have the extraordinary ability to turn into many other kinds of cells, giving researchers a tool to repair damaged organs and tissues. But that same ability to turn into other kinds of cells means that a pluripotent stem cell could also turn into a cancerous one, endangering someone’s life.

A*STAR

Researchers at the A*STAR Bioprocessing Technology Institute: Photo courtesy A*STAR

Now researchers at the Agency for Science, Technology and Research (A*STAR) in Singapore may have found a way to stop that happening.

When you change, or differentiate, stem cells into other kinds of cells there will always be some of the original material that didn’t make the transformation. Those cells could turn into tumors called teratomas. Scientists have long sought for a way to identify pluripotent cells that haven’t differentiated, without harming the ones that have.

The team at A*STAR injected mice with embryonic stem cells to generate antibodies. They then tested the ability of the different antibodies to destroy pluripotent stem cells. They found one, they called A1, that did just that; killing pluripotent cells but leaving other cells unharmed.

Further study showed that A1 worked by attaching itself to specific molecules that are only found on the surface of pluripotent cells.

In an article on Phys.Org Andre Choo, the leader of the team, says this gives them a tool to get rid of the undifferentiated cells that could potentially cause problems:

“That was quite exciting because it now gives us a view of the mechanism that is responsible for the cell-killing effect.”

Reviving hope for Parkinson’s patients:

In the 1980’s and 1990’s scientists transplanted fetal tissue into the brains of people with Parkinson’s disease. They hoped the cells in the tissue would replace the dopamine-producing cells destroyed by Parkinson’s, and stop the progression of the disease.

For some patients the transplants worked well. For some they produced unwanted side effects. But for most they had little discernible effect. The disappointing results pretty much brought the field to a halt for more than a decade.

But now researchers are getting ready to try again, and a news story on NPR explained why they think things could turn out differently this time.

tabar-viviane

Viviane Tabar, MD; Photo courtesy Memorial Sloan Kettering Cancer Center

Viviane Tabar, a stem cell researcher at Memorial Sloan Kettering Cancer Center in New York, says in the past the transplanted tissue contained a mixture of cells:

“What you were placing in the patient was just a soup of brain. It did not have only the dopamine neurons, which exist in the tissue, but also several different types of cells.”

This time Tabar and her husband, Lorenz Studer, are using only cells that have been turned into the kind of cell destroyed by the disease. She says that will, hopefully, make all the difference:

“So you are confident that everything you are putting in the patient’s brain will consist of  the right type of cell.”

Tabar and Studer are now ready to apply to the Food and Drug Administration (FDA) for permission to try their approach out in a clinical trial. They hope that could start as early as next year.

Hans runs for Congress:

Keirstead

Hans Keirstead: Photo courtesy Orange County Register

Hans Keirstead is a name familiar to many in the stem cell field. Now it could become familiar to a lot of people in the political arena too, because Keirstead has announced he’s planning to run for Congress.

Keirstead is considered by some to be a pioneer in stem cell research. A CIRM grant helped him develop a treatment for spinal cord injury.  That work is now in a clinical trial being run by Asterias. We reported on encouraging results from that trial earlier this week.

Over the years the companies he has founded – focused on ovarian, skin and brain cancer – have made him millions of dollars.

Now he says it’s time to turn his sights to a different stage, Congress. Keirstead has announced he is going to challenge 18-term Orange County Republican Dana Rohrabacher.

In an article in the Los Angeles Times, Keirstead says his science and business acumen will prove important assets in his bid for the seat:

“I’ve come to realize more acutely than ever before the deficits in Congress and how my profile can actually benefit Congress. I’d like to do what I’m doing but on a larger stage — and I think Congress provides that, provides a forum for doing the greater good.”

Stem cell repair of birth defect during pregnancy possible, rodent study shows

As far-fetched as it may sound, performing prenatal surgery on a fetus still growing inside its mother’s womb is actually possible. This specialized procedure is done to repair birth defects like spina bifida, in which a baby’s back bones don’t form properly around the spinal cord. This opening in the spine that leads to excess spinal fluid and leaves spinal cord nerve cells unprotected from the surrounding tissue.  These abnormalities can lead to brain damage, paralysis and loss of bladder control.

Although prenatal surgery to close up the defect can reduce future neurological problems in the child’s life, there is an increased danger of significant complications including preterm birth, separation of the placenta from the uterus and premature breaking on the amniotic membrane (ie breaking the mother’s water).

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Microscopy image of iSkin, three-dimensional cultured skin derived from human iPSCs. Credit: Kazuhiro Kajiwara.

A research team at Japan’s National Research Institute for Child Health and Development is trying to overcome these problems by developing a less invasive prenatal therapy for spina bifida using stem cells. And this week, they published a Stem Cell Reports study that shows encouraging preclinical results in rodents.

The most severe and common form of spina bifida called myelomeningocele usually leads to the formation of a fluid-filled bulge protruding from a newborn’s back. The team’s therapeutic approach is to graft 3D layers of stem cell-derived skin early in the pregnancy to prevent the bulge from forming in the first place. This minimally invasive procedure would hopefully be less risky than the surgical approach.

To demonstrate a proof of concept for this approach, skin graft experiments were performed on fetal rats that had myelomeningocele-like symptoms induced by the hormone retinoic acid. Human amniotic fluid cells collected from two pregnancies with severe fetal defects were used to derived human iPSCs which were then specialized into skin cells. Over a 14-week period – a timeline short enough to allow the eventual human procedure to be performed within the 28th to 29th week of pregnancy – the cells were grown into 3D layers they call, “iSkin”.

The iSkin grafts were transplanted in 20 fetal rats through a small cut into the wall of the uterus. At birth, the myelomeningocele defect in four rats was completely covered and partially covered in another eight rats. It’s encouraging to note that no tumors formed from the skin transplants, a concern when dealing with iPSC-derived cell therapies. In press release, team lead Dr. Akihiro Umezawa spoke about the promise of this approach but also the work that still lies ahead:

“We are encouraged by our results and believe that our fetal stem cell therapy has great potential to become a novel treatment for myelomeningocele. However, additional studies in larger animals are needed to demonstrate that our fetal stem cell therapy safely promotes long-term skin regeneration and neurological improvement.”

New stem cell technique gives brain support cells a starring role

Gage et al

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

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

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

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

Finding a better way

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

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

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

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

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

But wait, there’s more!

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

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

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