CCSF’s CIRM Bridges scholars: the future of stem cell research is in good hands

In need of an extra dose of inspiration? You might read a great book or listen to that podcast your friend recommended. You might even take a stroll along the beach. But I can do you one better: go to a conference poster session where young stem cell scientists describe their research.

That’s what I did last week at the City College of San Francisco’s (CCSF) Bioscience Symposium held at UC San Francisco’s Genentech Hall. It’s a day-long conference that showcases the work of CCSF Bioscience interns and gives them a chance to present the results of their research projects, network with their peers and researchers, hear panelists talk about careers in biotechnology and participate in practice job interviews.

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CCSF’s CIRM Bridges Scholars (clockwise from top left): Vanessa Lynn Herrara, Viktoriia Volobuieva, Christopher Nosworthy and Sofiana E. Hamama.

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CCSF’s CIRM Bridges Scholars (clockwise from top left): Seema Niddapu, Mark Koontz, Karolina Kaminska and Iris Avellano

Eight of the dozens of students in attendance at the Symposium are part of the CIRM-funded Bridges Stem Cell Internship program at CCSF. It’s one of 14 CIRM Bridges programs throughout the state that provides paid stem cell research internships to students at universities and colleges that don’t have major stem cell research programs. Each Bridges internship includes thorough hands-on training and education in stem cell research, and direct patient engagement and outreach activities that engage California’s diverse communities.

In the CCSF Bridges Program, directed by Dr. Carin Zimmerman, the students do a 9-month paid internship in top notch labs at UCSF, the Gladstone Institutes and Blood System Research Institute. As I walked from poster to poster and chatted with each Bridges scholar, their excitement and enthusiasm for carrying out stem cell research was plain to see. It left me with the feeling that the future of stem cell research is in good hands and, as I walked into the CIRM office the next day, I felt re-energized to tackle the Agency’s mission to accelerate stem cell treatment for patients with unmet medical needs. But don’t take my word for it, listen to the enthusiastic perspectives of Bridges scholars Mark Koontz and Iris Avellano in this short video.

Gladstone researchers tame toxic protein that carries increased Alzheimer’s risk

With a clinical trial failure rate of 99% over the past 15 years or so, the path to a cure for Alzheimer’s disease is riddled with disappointment. In many cases, candidate therapies looked very promising in pre-clinical animal studies, only to flop when tested in people. Now, a CIRM-funded Nature Medicine study by researchers at the Gladstone Institutes sheds some light on a source of this discrepancy. And more importantly, the study points to a potential treatment strategy that can remove the hallmarks of Alzheimer’s in human brain cells.

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Build up of tau protein (blue) and amyloid-beta (yellow) in and around neurons are hallmarks of the damage caused by Alzheimer’s disease. 
Image courtesy of the National Institute on Aging/National Institutes of Health.

For several decades, researchers have known the ApoE gene can influence the risk for an Alzheimer’s diagnosis in individuals 65 years and older. The gene comes in a few flavors with ApoE3 and ApoE4 differing in only one spot in their DNA sequences. Though nearly identical, the resulting ApoE3 and E4 proteins have very different shapes with differing function. In fact, people who inherit two copies of the ApoE4 gene have a twelve times higher risk for Alzheimer’s compared to those with the more common ApoE3.

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Yadong Huang

To better understand what’s happening at the cellular level, Yadong Huang, PhD and his team at the Gladstone Institutes obtained skin samples from Alzheimer’s donors carrying two copies of the ApoE4 gene and healthy donors with two copies of ApoE3. The skin cells were reprogrammed into induced pluripotent stem cells (iPSCs) and then matured into nerve cells, or neurons.

Compared to ApoE3 cells, the researchers observed that the ApoE4 neurons accumulated higher levels of proteins called p-tau and amyloid beta, which are hallmarks of Alzheimer’s disease. Repeating this same experiment in iPSC-derived mouse neurons showed no difference in the production of amyloid beta levels between the ApoE3 and E4 neurons. This result points to the importance of studying human disease in human cells, as first author Chengzhong Wang, PhD, points out in a press release:

“There’s an important species difference in the effect of apoE4 on amyloid beta. Increased amyloid beta production is not seen in mouse neurons and could potentially explain some of the discrepancies between mice and humans regarding drug efficacy. This will be very important information for future drug development.”

Further experiments aimed to answer a long sought-after question: is it the absence of ApoE3 or the presence of ApoE4 that causes the damaging effects on neurons? Using gene-editing techniques, the team removed both ApoE forms from the donor-derived neurons. The resulting cells appeared healthy but when ApoE4 was added back in, Alzheimer’s-associated problems emerged. This finding points to the toxicity of ApoE4 to neurons.

With this new insight in hand, the team examined what would happen if they converted the ApoE4 form into the ApoE3 form. The team had previously designed molecules, they dubbed “structure correctors”, that physically interact with the ApoE4 protein and cause it to take on the shape of the ApoE3 form found in healthy individuals. When these correctors were added to the ApoE4 neurons, it brought back normal function to the cells.

Given that the structure corrector is a chemical compound that works in human brain cells, it’s tantalizing to think about its possible use as a novel Alzheimer’s drug. And you can bet Dr. Huang and his group are eagerly embarking on that new path.

Gladstone scientists tackle heart failure by repairing the heart from within

Modern medicine often involves the development of a drug or treatment outside the body, which is then given to a patient to fix, improve or even prevent their condition. But what if you could regenerate or heal the body using the cells and tissue already inside a patient?

Scientists at the Gladstone Institutes are pursuing such a strategy for heart disease. In a CIRM-funded study published today in the journal Cell, the team identified four genes that can stimulate adult heart muscle cells, called cardiomyocytes, to divide and proliferate within the hearts of living mice. This discovery could be further developed as a strategy to repair cardiac tissue damage caused by heart disease and heart attacks.

Regenerating the Heart

Heart disease is the leading cause of death in the US and affects over 24 million people around the world. When patients experience a heart attack, blood flow is restricted to the heart, and parts of the heart muscle are damaged or die due to the lack of oxygen. The heart is unable to regenerate new healthy heart muscle, and instead, cardiac fibroblasts generate fibrous scar tissue to heal the injury. This scar tissue impairs the heart’s ability to pump blood, causing it to work harder and putting patients at risk for future heart failure.

Deepak Srivastava, President of the Gladstone Institutes and a senior investigator there, has dedicated his life’s research to finding new ways to regenerate heart tissue. Previously, his team developed methods to reprogram mouse and human cardiac fibroblasts into beating cardiomyocytes in hopes of one day restoring heart function in patients. The team is advancing this research with the help of a CIRM Discovery Stage research grant, which will aid them in developing a gene therapy product that delivers reprogramming factors into scar tissue cells to regenerate new heart muscle.

In this new study, Srivastava took a slightly different approach and attempted to coax cardiomyocytes, rather than cardiac fibroblasts, to divide and regenerate the heart. During development, fetal cardiomyocytes rapidly divide to create heart tissue. This regenerative ability is lost in adult cardiomyocytes, which are unable to divide because they’ve already exited the cell cycle (a series of phases that a cell goes through that ultimately results in its division).

Deepak Srivastava (left) and first author Tamer Mohamed (right). Photo credits: Diana Rothery.

Unlocking proliferative potential

Srivastava had a hunch that genes specifically involved in the cell division could be used to jump-start an adult cardiomyocyte’s re-entry into the cell cycle. After some research, they identified four genes (referred to as 4F) involved in controlling cell division. When these genes were turned on in adult cardiomyocytes, the cells started to divide and create new heart tissue.

This 4F strategy worked in mouse and rat cardiomyocytes and also was successful in stimulating cell division in 15%-20% of human cardiomyocytes. When they injected 4F into the hearts of mice that had suffered heart attacks, they observed an improvement in their heart function after three months and a reduction in the size of the scar tissue compared to mice that did not receive the injection.

The team was able to further refine their method by replacing two of the four genes with chemical inhibitors that had similar functions. Throughout the process, the team did not observe the development of heart tumors caused by the 4F treatment. They attributed this fact to the short-term expression of 4F in the cardiomyocytes. However, Srivastava expressed caution towards using this method in a Gladstone news release:

“In human organs, the delivery of genes would have to be controlled carefully, since excessive or unwanted cell division could cause tumors.”

First stop heart, next stop …

This study suggests that it’s possible to regenerate our tissues and organs from within by triggering adult cells to re-enter the cell cycle. While more research is needed to ensure this method is safe and worthy of clinical development, it could lead to a regenerative treatment strategy for heart failure.

Srivastava will continue to unravel the secrets to the proliferative potential of cardiomyocytes but predicts that other labs will pursue similar methods to test the regenerative potential of adult cells in other tissues and organs.

“Heart cells were particularly challenging because when they exit the cell cycle after birth, their state is really locked down—which might explain why we don’t get heart tumors. Now that we know our method is successful with this difficult cell type, we think it could be used to unlock other cells’ potential to divide, including nerve cells, pancreatic cells, hair cells in the ear, and retinal cells.”


Related Links:

Stem Cell Roundup: Rainbow Sherbet Fruit Fly Brains, a CRISPR/iPSC Mash-up and more

This week’s Round Up is all about the brain with some CRISPR and iPSCs sprinkled in:

Our Cool Stem Cell Image of the Week comes from Columbia University’s Zuckerman Institute:

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(Credit: Jon Enriquez/Mann Lab/Columbia’s Zuckerman Institute).

This rainbow sherbet-colored scientific art is a microscopy image of a fruit fly nervous system in which brain cells were randomly labeled with different colors. It was a figure in a Neuron study published this week showing how cells derived from the same stem cells can go down very different developmental paths but then later are “reunited” to carry out key functions, such as in this case, the nervous system control of leg movements.


A new therapeutic avenue for Parkinson’s diseaseBuck Institute

Many animal models of Parkinson’s disease are created by mutating specific genes to cause symptoms that mimic this incurable, neurodegenerative disorder. But, by far, most cases of Parkinson’s are idiopathic, a fancy term for spontaneous with no known genetic cause. So, researchers at the Buck Institute took another approach: they generated a mouse model of Parkinson’s disease using the pesticide, paraquat, exposure to which is known to increase the risk of the idiopathic form of Parkinson’s.

Their CIRM-funded study in Cell Reports showed that exposure to paraquat leads to cell senescence – in which cells shut down and stop dividing – particularly in astrocytes, brain cells that support the function of nerve cells. Ridding the mice of these astrocytes relieved some of the Parkinson’s like symptoms. What makes these results so intriguing is the team’s analysis of post-mortem brains from Parkinson’s patients also showed the hallmarks of increased senescence in astrocytes. Perhaps, therapeutic approaches that can remove senescent cells may yield novel Parkinson’s treatments.


Discovery may advance neural stem cell treatments for brain disordersSanford-Burnham Prebys Medical Discovery Institute (via Eureka Alert)

Another CIRM-funded study published this week in Nature Neuroscience may also help pave the way to new treatment strategies for neurologic disorders like Parkinson’s disease. A team at Sanford Burnham Prebys Medical Discovery Institute (SBP) discovered a novel gene regulation system that brain stem cells use to maintain their ability to self-renew.

The study centers around messenger RNA, a molecular courier that transcribes a gene’s DNA code and carries it off to be translated into a protein. The team found that the removal of a chemical tag on mRNA inside mouse brain stem cells caused them to lose their stem cell properties. Instead, too many cells specialized into mature brain cells leading to abnormal brain development in animal studies. Team lead Jing Crystal Zhao, explained how this finding is important for future therapeutic development:

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Crystal Zhao

“As NSCs are increasingly explored as a cell replacement therapy for neurological disorders, understanding the basic biology of NSCs–including how they self-renew–is essential to harnessing control of their in vivo functions in the brain.”


Researchers Create First Stem Cells Using CRISPR Genome ActivationThe Gladstone Institutes

Our regular readers are most likely familiar with both CRISPR gene editing and induced pluripotent stem cell (iPSC) technologies. But, in case you missed it late last week, a Cell Stem Cell study out of Sheng Ding’s lab at the Gladstone Institutes, for the first time, combined the two by using CRISPR to make iPSCs. The study got a lot of attention including a review by Paul Knoepfler in his blog The Niche. Check it out for more details!

 

CIRM interviews Lorenz Studer: 2017 recipient of the Ogawa-Yamanaka Stem Cell Prize [Video]

For eight long years, researchers who were trying to develop a stem cell-based therapy for Parkinson’s disease – an incurable movement disorder marked by uncontrollable shaking, body stiffness and difficulty walking – found themselves lost in the proverbial wilderness. In initial studies, rodent stem cells were successfully coaxed to specialize into dopamine-producing nerve cells, the type that are lost in Parkinson’s disease. And further animal studies showed these cells could treat Parkinson’s like symptoms when transplanted into the brain.

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Lorenz Studer, MD
Photo Credit: Sloan Kettering

But when identical recipes were used to make human stem cell-derived dopamine nerve cells the same animal experiments didn’t work. By examining the normal developmental biology of dopamine neurons much more closely, Lorenz Studer cracked the case in 2011. Now seven years later, Dr. Studer, director of the Center for Stem Cell Biology at the Memorial-Sloan Kettering Cancer Center, and his team are on the verge of beginning clinical trials to test their Parkinson’s cell therapy in patients

It’s for these bottleneck-busting contributions to the stem cell field that Dr. Studer was awarded the Gladstone Institutes’ 2017 Ogawa-Yamanaka Stem Cell Prize. Now in its third year, the prize was founded by philanthropists Hiro and Betty Ogawa along with  Shinya Yamanaka, Gladstone researcher and director of the Center for iPS Cell Research and Application at Kyoto University, and is meant to inspire and celebrate discoveries that build upon Yamanaka’s Nobel prize winning discovery of induced pluripotent stem cells (iPSCs).

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(L to R) Shinya Yamanaka, Andrew Ogawa, Deepak Srivastava present Lorenz Studer the 2017 Ogawa-Yamanaka Stem Cell Prize at Gladstone Institutes. Photo Credit: Todd Dubnicoff/CIRM

Studer was honored at the Gladstone in November and presented the Ogawa-Yamanka Stem Cell Prize Lecture. He was kind enough to sit down with me for a brief video interview (watch it below) a few minutes before he took the stage. He touched upon his Parkinson’s disease research as well as newer work related to hirschsprung disease, a dangerous intestinal disorder often diagnosed at birth that is caused by the loss of nerve cells in the gut. Using human embryonic stem cells and iPSCs derived from hirschsprung patients, Studer’s team has worked out the methods for making the gut nerve cells that are lost in the disease. This accomplishment has allowed his lab to better understand the disease and to make solid progress toward a stem cell-based therapy.

His groundbreaking work has also opened up the gates for other Parkinson’s researchers to make important insights in the field. In fact, CIRM is funding several interesting early stage projects aimed at moving therapy development forward:

We posted the 8-minute video with Dr. Studer today on our official YouTube channel, CIRM TV. You can watch the video here:

And for a more detailed description of Studer’s research, watch Gladstone’s webcast recording of his entire lecture:

Stem Cell Stories that Caught Our Eye: New law to protect consumers; using skin to monitor blood sugar; and a win for the good guys

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State Senator Ed Hernandez

New law targets stem cell clinics that offer therapies not approved by the FDA

For some time now CIRM and others around California have been warning consumers about the risks involved in going to clinics that offer stem cell therapies that have not been tested in a clinical trial or approved by the U.S. Food and Drug Administration (FDA) for use in patients.

Now a new California law, authored by State Senator Ed Hernandez (D-West Covina) attempts to address that issue. It will require medical clinics whose stem cell treatments are not FDA approved, to post notices and provide handouts to patients warning them about the potential risk.

In a news release Sen. Hernandez said he hopes the new law, SB 512, will protect consumers from early-stage, unproven experimental therapies:

“There are currently over 100 medical offices in California providing non-FDA approved stem cell treatments. Patients spend thousands of dollars on these treatments, but are totally unaware of potential risks and dangerous side effects.”

Sen. Hernandez’s staffer Bao-Ngoc Nguyen crafted the bill, with help from CIRM Board Vice Chair Sen. Art Torres, Geoff Lomax and UC Davis researcher Paul Knoepfler, to ensure it targeted only clinics offering non-FDA approved therapies and not those offering FDA-sanctioned clinical trials.

For example the bill would not affect CIRM’s Alpha Stem Cell Clinic Network because all the therapies offered there have been given the green light by the FDA to work with patients.

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Using your own skin as a blood glucose monitor

One of the many things that people with diabetes hate is the constant need to monitor their blood sugar level. Usually that involves a finger prick to get a drop of blood. It’s simple but not much fun. Attempts to develop non-invasive monitors have been tried but with limited success.

Now researchers at the University of Chicago have come up with another alternative, using the person’s own skin to measure their blood glucose level.

Xiaoyang Wu and his team accomplished this feat in mice by first creating new skin from stem cells. Then, using the gene-editing tool CRISPR, they added in a protein that sticks to sugar molecules and another protein that acts as a fluorescent marker. The hope was that the when the protein sticks to sugar in the blood it would change shape and emit fluorescence which could indicate if blood glucose levels were too high, too low, or just right.

The team then grafted the skin cells back onto the mouse. When those mice were left hungry for a while then given a big dose of sugar, the skin “sensors” reacted within 30 seconds.

The researchers say they are now exploring ways that their findings, published on the website bioRxiv, could be duplicated in people.

While they are doing that, we are supporting ViaCytes attempt to develop a device that doesn’t just monitor blood sugar levels but also delivers insulin when needed. You can read about our recent award to ViaCyte here.

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Dr. Deepak Srivastava

Stem Cell Champion, CIRM grantee, and all-round-nice guy named President of Gladstone Institutes

I don’t think it would shock anyone to know that there are a few prima donnas in the world of stem cell research. Happily, Dr. Deepak Srivastava is not one of them, which makes it such a delight to hear that he has been appointed as the next President of the Gladstone Institutes in San Francisco.

Deepak is a gifted scientist – which is why we have funded his work – a terrific communicator and a really lovely fella; straight forward and down to earth.

In a news release announcing his appointment – his term starts January 1 next year – Deepak said he is honored to succeed the current President, Sandy Williams:

“I joined Gladstone in 2005 because of its unique ability to leverage diverse basic science approaches through teams of scientists focused on achieving scientific breakthroughs for mankind’s most devastating diseases. I look forward to continue shaping this innovative approach to overcome human disease.”

We wish him great success in his new role.

 

 

 

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.

Treatments, cures and clinical trials: an in-person update on CIRM’s progress

Patients and Patient Advocates are at the heart of everything we do at CIRM. That’s why we are holding three free public events in the next few months focused on updating you on the stem cell research we are funding, and our plans for the future.

Right now we have 33 projects that we have funded in clinical trials. Those range from heart disease and stroke, to cancer, diabetes, ALS (Lou Gehrig’s disease), two different forms of vision loss, spinal cord injury and HIV/AIDS. We have also helped cure dozens of children battling deadly immune disorders. But as far as we are concerned we are only just getting started.

Over the course of the next few years, we have a goal of adding dozens more clinical trials to that list, and creating a pipeline of promising therapies for a wide range of diseases and disorders.

That’s why we are holding these free public events – something we try and do every year. We want to let you know what we are doing, what we are funding, how that research is progressing, and to get your thoughts on how we can improve, what else we can do to help meet the needs of the Patient Advocate community. Your voice is important in helping shape everything we do.

The first event is at the Gladstone Institutes in San Francisco on Wednesday, September 6th from noon till 1pm. The doors open at 11am for registration and a light lunch.

Gladstone Institutes

Here’s a link to an Eventbrite page that has all the information about the event, including how you can RSVP to let us know you are coming.

We are fortunate to be joined by two great scientists, and speakers – as well as being CIRM grantees-  from the Gladstone Institutes, Dr. Deepak Srivastava and Dr. Steve Finkbeiner.

Dr. Srivastava is working on regenerating heart muscle after it has been damaged. This research could not only help people recover from a heart attack, but the same principles might also enable us to regenerate other organs damaged by disease. Dr. Finkbeiner is a pioneer in diseases of the brain and has done ground breaking work in both Alzheimer’s and Huntington’s disease.

We have two other free public events coming up in October. The first is at UC Davis in Sacramento on October 10th (noon till 1pm) and the second at Cedars-Sinai in Los Angeles on October 30th (noon till 1pm). We will have more details on these events in the coming weeks.

We look forward to seeing you at one of these events and please feel free to share this information with anyone you think might be interested in attending.

Stem cell stories that caught our eye: skin grafts fight diabetes, reprogramming the immune system, and Asterias expands spinal cord injury trial sites

Here are the stem cell stories that caught our eye this week.

Skin grafts fight diabetes and obesity.

An interesting new gene therapy strategy for fighting type 1 diabetes and obesity surfaced this week. Scientists from the University of Chicago made genetically engineered skin grafts that secrete a peptide hormone called glucagon-liked peptide-1 (GLP-1). This peptide is released by cells in the intestine and can lower blood sugar levels by stimulating pancreatic islet cells to secrete insulin (a hormone that promotes the absorption of glucose from the blood).

The study, which was published in the journal Cell Stem Cell, used CRISPR gene editing technology to introduce a mutation to the GLP-1 gene in mouse and human skin stem cells. This mutation stabilized the GLP-1 peptide, allowing it to hang around in the blood for longer. The team matured these stem cells into skin grafts that secreted the GLP-1 into the bloodstream of mice when treated with a drug called doxycycline.

When fed a high-fat diet, mice with a skin graft (left), genetically altered to secrete GLP-1 in response to the antibiotic doxycycline, gained less weight than normal mice (right). (Image source: Wu Laboratory, the University of Chicago)

On a normal diet, mice that received the skin graft saw a rise in their insulin levels and a decrease in their blood glucose levels, proving that the gene therapy was working. On a high fat diet, mice with the skin graft became obese, but when they were treated with doxycycline, GLP-1 secreted from their grafts reduced the amount of weight gain. So not only does their engineered skin graft technology look like a promising new strategy to treat type 1 diabetes patients, it also could be used to control obesity. The beauty of the technology is in its simplicity.

An article in Genetic Engineering and Biotechnology News that covered this research explained that Xiaoyang Wu, the senior author on the study, and his team “worked with skin because it is a large organ and easily accessible. The cells multiply quickly and are easily transplanted. And, transplanted cells can be removed, if needed. “Skin is such a beautiful system,” Wu says, noting that its features make it a perfect medium for testing gene therapies.”

Wu concluded that, “This kind of therapy could be potentially effective for many metabolic disorders.” According to GenBio, Wu’s team “is now testing the gene-therapy technique in combination with other medications.” They also hope that a similar strategy could be used to treat patients that can’t make certain proteins like in the blood clotting disorder hemophilia.

How to reprogram your immune system (Kevin McCormack)

When your immune system goes wrong it can cause all manner of problems, from type 1 diabetes to multiple sclerosis and cancer. That’s because an overactive immune system causes the body to attack its own tissues, while an underactive one leaves the body vulnerable to outside threats such as viruses. That’s why scientists have long sought ways to correct those immune dysfunctions.

Now researchers at the Gladstone Institutes in San Francisco think they have found a way to reprogram specific cells in the immune system and restore a sense of health and balance to the body. Their findings are published in the journal Nature.

The researchers identified a drug that targets effector T cells, which get our immune system to defend us against outside threats, and turns them into regulatory T cells, which control our immune system and stops it from attacking our own body.

Why would turning one kind of T cell into another be helpful? Well, in some autoimmune diseases, the effector T cells become overly active and attack healthy tissues and organs, damaging and even destroying them. By converting them to regulatory T cells you can prevent that happening.

In addition, some cancers can hijack regulatory T cells and suppress the immune system, allowing the disease to spread. By turning those cells into effector T cells, you can boost the immune system and give it the strength to fight back and, hopefully, kill the cancer.

In a news release, Gladstone Senior Investigator Sheng Ding, the lead scientists on the study, said their findings could have several applications:

“Our findings could have a significant impact on the treatment of autoimmune diseases, as well as on stem cell and immuno-oncology therapies.” 

Gladstone scientists Sheng Ding (right) and Tao Xu (left) discovered how to reprogram cells in our immune system. (Gladstone Institutes)

CIRM-funded spinal cord injury trial expands clinical sites

We have another update from CIRM’s clinical trial front. Asterias Biotherapeutics, which is testing a stem cell treatment for complete cervical (neck) spinal cord injury, is expanding its clinical sites for its CIRM-funded SCiStar Phase 1/2a trial. The company is currently treating patients at six sites in the US, and will be expanding to include two additional sites at Thomas Jefferson University Hospital in Philadelphia and the UC San Diego Medical Center, which is part of the UCSD Health CIRM Alpha Stem Cell Clinic.

In a company news release, Ed Wirth, Chief Medical Officer of Asterias said,

Ed Wirth

“We are excited about the clinical site openings at Thomas Jefferson University Hospital and UC San Diego Health. These sites provide additional geographical reach and previous experience with spinal cord injury trials to our SCiStar study. We have recently reported completion of enrollment in four out of five cohorts in our SCiStar study so we hope these institutions will also participate in a future, larger study of AST-OPC1.”

The news release also gave a recap of the trial’s positive (but still preliminary) results this year and their plans for completing trial enrollment.

“In June 2017, Asterias reported 9 month data from the AIS-A 10 million cell cohort that showed improvements in arm, hand and finger function observed at 3-months and 6-months following administration of AST-OPC1 were confirmed and in some patients further increased at 9-months. The company intends to complete enrollment of the entire SCiStar study later this year, with multiple safety and efficacy readouts anticipated during the remainder of 2017 and 2018.”

Stem Cell Roundup: Battle of the Biotech Bands, “Cells I See” Art Contest and Teaching Baseball Fans the Power of Stem Cells

This Friday’s stem cell roundup is dedicated to the playful side of stem cell science. Scientists are often stereotyped as lab recluses who honorably forgo social lives in the quest to make game-changing discoveries and advance cutting-edge research. But as a former bench scientist, I can attest that scientists are normal people too. They might have a nerdy, slightly neurotic side around their field of research, but they know how to enjoy life and have fun. So here are a few stories that caught our eye this week about scientists having a good time with science.

Rockin’ researchers battle for glory (Kevin McCormack)

Did you know that Bruce Springsteen got his big break after winning the Biotech Battle of the Bands (BBOB)? Probably not, I just made that up. But just because Bruce didn’t hit it big because of BBOB doesn’t mean you can’t.

BBOB is a fun chance for you and your labmates, or research partners, to cast off your lab coats, pick up a guitar, form a band, show off your musical chops, play before a live audience and raise money for charity.  This is the fourth year the event is being held. It’s part of Biotech Week Boston, on Wednesday, September 27th at the Royale Nightclub, Boston.

Biotech Week is a celebration of science and, duh, biotech; bringing together what the event organizers call “the most inventive scientific minds and business leaders in Boston and around the world.” And they wouldn’t lie would they, after all, they’re scientists.

If you want to check out the competition here’s some video from a previous year – see if you can spot the man with the cowbell!

“Cells I See” Stem Cell Art Contest

It’s that time again! The “Cells I See” art contest hosted by Canada’s Centre for Commercialization for Regenerative Medicine (CCRM) and The Stem Cell Network is now open for business. This is a super fun event that celebrates the beauty of stem cells and biomaterials that support regenerative medicine.

Not only is “Cells I See” a great way for scientists to share their research with the public, it’s also a way for them to tap into their artistic, creative side. Last year’s ­contestants submitted breathtaking microscope images, paintings and graphic designs of stem cells in action. The titles for these art submissions were playful. “Nucleic Shower” “The Quest for Innervation” and “Flat, Fluorescent & Fabulous” were some of my favorite title entries.

There are two prizes for this contest. The grand prize of $750 will be awarded to the submission with the highest number of votes from scientists attending the Till and McCulloch Stem Cell Meeting in November. There is also a “People’s Choice” prize of $500 given to the contestant who has the most numbers of likes on the CCRM Facebook page.

The deadline for “Cell I See” submissions is September 8th so you have plenty of time to get your creative juices flowing!

Iris

The 2016 Grand Prize and People’s Choice Winner, Sabiha Hacibekiroglu, won for her photo titled “Iris”.

Scientists Teach Baseball Fans the Power of Stem Cells

San Francisco Giants fans who attended Tuesday’s ball game were in for a special treat – a science treat that is. Researchers from the Gladstone Institutes partnered with the SF Giants to raise awareness about the power of stem cells for advancing research and developing cures for various diseases.

Gladstone PhD student Jessica Butts explains the Stem Cell Plinko game to a Giants fan.

The Gladstone team had a snazzy stem cell booth at the Giant’s Community Clubhouse with fun science swag and educational stem cell activities for fans of all ages. One of the activities was a game called “Stem Cell Plinko” where you drop a ball representing a pluripotent stem cell down a plinko board. The path the ball travels represents how that stem cell differentiates or matures into adult cells like those in the heart.

Gladstone also debuted their new animated stem cell video, which explains how “stem cell research has opened up promising avenues for personalized and regenerative medicine.”

Finally, Gladstone scientists challenged fans to participate in a social media contest about their newfound stem cell knowledge cells on Twitter. The winner of the contest, a woman named Nicole, will get an exclusive, behind-the-scenes lab tour at the Gladstone and “see firsthand how Gladstone is using stem cells to overcome disease.”

The Gladstone “Power of Stem Cells” event is a great example of how scientists are trying to make research and science more accessible to the public. It not only benefits people by educating them about the current state of stem cell research, but also is a fun way for scientists to engage with the local community.

“Participating in the SF Giants game was very fun,” said Megan McDevitt, vice president of communications at the Gladstone Institutes. “Our booth experienced heavy traffic all evening, giving us a wonderful opportunity to engage with the San Francisco community about science and, more specifically, stem cell research. We were delighted to see how interested fans were to learn more on the topic.”

And as if all that wasn’t enough, the Giants won, something that hasn’t been happening very much this season.

Go Giants. Go Gladstone.

Gladstone scientist dropping stem cell knowledge to Giants fans.