Scientists make stem cell-derived nerve cells damaged in spinal cord injury

The human spinal cord is an information highway that relays movement-related instructions from the brain to the rest of the body and sensory information from the body back to the brain. What keeps this highway flowing is a long tube of nerve cells and support cells bundled together within the spine.

When the spinal cord is injured, the nerve cells are damaged and can die – cutting off the flow of information to and from the brain. As a result, patients experience partial or complete paralysis and loss of sensation depending on the extent of their injury.

Unlike lizards which can grow back lost tails, the spinal cord cannot robustly regenerate damaged nerve cells and recreate lost connections. Because of this, scientists are looking to stem cells for potential solutions that can rebuild injured spines.

Making spinal nerve cells from stem cells

Yesterday, scientists from the Gladstone Institutes reported that they used human pluripotent stem cells to create a type of nerve cell that’s damaged in spinal cord injury. Their findings offer a new potential stem cell-based strategy for restoring movement in patients with spinal cord injury. The study was led by Gladstone Senior Investigator Dr. Todd McDevitt, a CIRM Research Leadership awardee, and was published in the journal Proceedings of the National Academy of Sciences.

The type of nerve cell they generated is called a spinal interneuron. These are specialized nerve cells in the spinal cord that act as middlemen – transporting signals between sensory neurons that connect to the brain to the movement-related, or motor, neurons that connect to muscles. Different types of interneurons exist in the brain and spinal cord, but the Gladstone team specifically created V2a interneurons, which are important for controlling movement.

V2a interneurons extend long distances in the spinal cord. Injuries to the spine can damage these important cells, severing the connection between the brain and the body. In a Gladstone news release, Todd McDevitt explained why his lab is particularly interested in making these cells to treat spinal cord injury.

Todd McDevitt, Gladstone Institutes

“Interneurons can reroute after spinal cord injuries, which makes them a promising therapeutic target. Our goal is to rewire the impaired circuitry by replacing damaged interneurons to create new pathways for signal transmission around the site of the injury.”

 

Transplanting nerve cells into the spines of mice

After creating V2a interneurons from human stem cells using a cocktail of chemicals in the lab, the team tested whether these interneurons could be successfully transplanted into the spinal cords of normal mice. Not only did the interneurons survive, they also set up shop by making connections with other nerve cells in the spinal cord. The mice that received the transplanted cells didn’t show differences in their movement suggesting that the transplanted cells don’t cause abnormalities in motor function.

Co-author on the paper, Dylan McCreedy, described how the transplanted stem cell-derived cells behaved like developing V2a interneurons in the spine.

“We were very encouraged to see that the transplanted cells sprouted long distances in both directions—a key characteristic of V2a interneurons—and that they started to connect with the relevant host neurons.”

Todd McDevitt (right), Jessica Butts (center) and Dylan McCreedy (left) created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. (Photo: Chris Goodfellow, Gladstone)

A new clinical strategy?

Looking forward, the Gladstone team plans to test whether these V2a interneurons can improve movement in mice with spinal cord injury. If results look promising in mice, this strategy of transplanting V2a interneurons could be translated into human clinic trials although much more time and research are needed to get there.

Trials testing stem cell-based treatments for spinal cord injury are already ongoing. Many of them involve transplanting progenitor cells that develop into the different types of cells in the spine, including nerve and support cells. These progenitor cells are also thought to secrete important growth factors that help regenerate damaged tissue in the spine.

CIRM is funding one such clinical trial sponsored by Asterias Biotherapeutics. The company is transplanting oligodendrocyte progenitor cells (which make nerve support cells called oligodendrocytes) into patients with severe spinal cord injuries in their neck. The trial has reported encouraging preliminary results in all six patients that received a dose of 10 million cells. You can read more about this trial here.

What the Gladstone study offers is a different stem cell-based strategy for treating spinal cord injury – one that produces a specific type of spinal nerve cell that can reestablish important connections in the spinal cord essential for movement.

For more on this study, watch the Gladstone’s video abstract “Discovery Offers New Hope to Repair Spinal Cord.


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Telomere length matters: scientists find shorter telomeres may cause aging-related disease

Aging is inevitable no matter how much you exercise, sleep or eat healthy. There is no magic pill or supplement that can thwart growing older. However, preventing certain age-related diseases is a different story. Genetic mutations can raise the risk of acquiring age-related diseases like heart disease, diabetes, cancer and dementia. And scientists are on the hunt for treatments that target these mutations in hopes of preventing these diseases from happening.

Telomeres shown in white act as protective caps at the ends of chromosomes.

Another genetic component that can accelerate diseases of aging are telomeres. These are caps made up of repeat sequences of DNA that sit at the ends of chromosomes and prevent the loss of important genetic material housed within chromosomes. Healthy cells have long telomeres, and ascells divide these telomeres begin to shorten. If telomere shortening is left unchecked, cells become unhealthy and either stop growing or self-destruct.

Cells have machinery to regrow their telomeres, but in most cases, the machinery isn’t activated and over time, the resulting shortened telomeres can lead to problems like an impaired immune system and organ degeneration. Shortened telomeres are associated with age-related diseases, but the reasons why have remained elusive until recently.

Scientists from the Gladstone Institutes have found a clue to this telomere puzzle that they shared in a study published yesterday in the Journal of Clinical Investigation. This research was funded in part by a CIRM Discovery stage award.

In their study, the team found that mice with a mutation that causes a heart condition known as calcific aortic valve disease (CAVD) were more likely to get the disease if they had short telomeres. CAVD causes the heart valves and vessels to turn hard as rock due to a buildup of calcium. It’s the third leading cause of heart disease and the only effective treatment requires surgery to replace the calcified parts of the heart.

Old age and mutations in one of the copies of the NOTCH1 gene can cause CAVD in humans. However, attempts to model CAVD in mice using the same NOTCH1 mutation have failed to produce symptoms of the disease. The team at Gladstone knew that mice inherently have longer telomeres than humans and hypothesized that these longer telomeres could protect mice with the NOTCH1 mutation from getting CAVD.

They decided to study NOTCH1 mutant mice that had short telomeres and found that these mice had symptoms of CAVD including hardened arteries. Furthermore, mice that had the shortest telomeres had the most severe heart-related symptoms.

First author on the study Christina Theodoris, explained in a Gladstone news release how telomere length matters in animal models of age-related diseases:

“Our findings reveal a critical role for telomere length in a mouse model of age-dependent human disease. This model provides a unique opportunity to dissect the mechanisms by which telomeres affect age-dependent disease and also a system to test novel therapeutics for aortic valve disease.”

Deepak Srivastava and Christina Theodoris created mouse models of CAVD that may be used to test drug therapies for the disease. (Photo: Chris Goodfellow, Gladstone Institutes)

The team believes that there is a direct relationship between short telomeres and CAVD, likely through alterations in the activity of gene networks related to CAVD. They also propose that telomere length could influence how severe the symptoms of this disease manifest in humans.

This study is important to the field because it offers a new strategy to study age-related diseases in animal models. Senior author on the study, Dr. Deepak Srivastava, elaborated on this concept:

Deepak Srivastava, Gladstone Institutes

“Historically, we have had trouble modeling human diseases caused by mutation of just one copy of a gene in mice, which impedes research on complex conditions and limits our discovery of therapeutics. Progressive shortening of longer telomeres that are protective in mice not only reproduced the clinical disease caused by NOTCH1 mutation, it also recapitulated the spectrum of disease severity we see in humans.”

Going forward, the Gladstone team will use their new mouse model of CAVD to test drug candidates that have the potential to treat CAVD in humans. If you want to learn more about this study, watch this Gladstone video featuring an interview of Dr. Srivastava about this publication.

Using stem cells to fix bad behavior in the brain

 

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Gladstone Institutes Steven Finkbeiner and Gaia Skibinski: Photo courtesy Chris Goodfellow, Gladstone Institutes

Diseases of the brain have many different names, from Alzheimer’s and Parkinson’s to ALS and Huntington’s, but they often have similar causes. Researchers at the Gladstone Institutes in San Francisco are using that knowledge to try and find an approach that might be effective against all of these diseases. In a new CIRM-funded study, they have identified one protein that could help do just that.

Many neurodegenerative diseases are caused by faulty proteins, which start to pile up and cause damage to neurons, the brain cells that are responsible for processing and transmitting information. Ultimately, the misbehaving proteins cause those cells to die.

The researchers at the Gladstone found a way to counter this destructive process by using a protein called Nrf2. They used neurons from humans (made from induced pluripotent stem cells – iPSCs – hence the stem cell connection here) and rats. They then tested these cells in neurons that were engineered to have two different kinds of mutations found in  Parkinson’s disease (PD) plus the Nrf2 protein.

Using a unique microscope they designed especially for this study, they were able to track those transplanted neurons and monitor what happened to them over the course of a week.

The neurons that expressed Nrf2 were able to render one of those PD-causing proteins harmless, and remove the other two mutant proteins from the brain cells.

In a news release to accompany the study in The Proceedings of the National Academy of Sciences, first author Gaia Skibinski, said Nrf2 acts like a house-cleaner brought in to tidy up a mess:

“Nrf2 coordinates a whole program of gene expression, but we didn’t know how important it was for regulating protein levels until now. Over-expressing Nrf2 in cellular models of Parkinson’s disease resulted in a huge effect. In fact, it protects cells against the disease better than anything else we’ve found.”

Steven Finkbeiner, the senior author on the study and a Gladstone professor, said this model doesn’t just hold out hope for treating Parkinson’s disease but for treating a number of other neurodegenerative problems:

“I am very enthusiastic about this strategy for treating neurodegenerative diseases. We’ve tested Nrf2 in models of Huntington’s disease, Parkinson’s disease, and ALS, and it is the most protective thing we’ve ever found. Based on the magnitude and the breadth of the effect, we really want to understand Nrf2 and its role in protein regulation better.”

The next step is to use this deeper understanding to identify other proteins that interact with Nrf2, and potentially find ways to harness that knowledge for new therapies for neurodegenerative disorders.

Translating great stem cell ideas into effective therapies

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CIRM funds research trying to solve the Alzheimer’s puzzle

In science, there are a lot of terms that could easily mystify people without a research background; “translational” is not one of them. Translational research simply means to take findings from basic research and advance them into something that is ready to be tested in people in a clinical trial.

Yesterday our Governing Board approved $15 million in funding for four projects as part of our Translational Awards program, giving them the funding and support that we hope will ultimately result in them being tested in people.

Those projects use a variety of different approaches in tackling some very different diseases. For example, researchers at the Gladstone Institutes in San Francisco received $5.9 million to develop a new way to help the more than five million Americans battling Alzheimer’s disease. They want to generate brain cells to replace those damaged by Alzheimer’s, using induced pluripotent stem cells (iPSCs) – an adult cell that has been changed or reprogrammed so that it can then be changed into virtually any other cell in the body.

CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs and Alzheimer’s – which has no cure and no effective long-term treatments – clearly represents an unmet medical need.

Another project approved by the Board is run by a team at Children’s Hospital Oakland Research Institute (CHORI). They got almost $4.5 million for their research helping people with sickle cell anemia, an inherited blood disorder that causes intense pain, and can result in strokes and organ damage. Sickle cell affects around 100,000 people in the US, mostly African Americans.

The CHORI team wants to use a new gene-editing tool called CRISPR-Cas9 to develop a method of editing the defective gene that causes Sickle Cell, creating a healthy, sickle-free blood supply for patients.

Right now, the only effective long-term treatment for sickle cell disease is a bone marrow transplant, but that requires a patient to have a matched donor – something that is hard to find. Even with a perfect donor the procedure can be risky, carrying with it potentially life-threatening complications. Using the patient’s own blood stem cells to create a therapy would remove those complications and even make it possible to talk about curing the disease.

While damaged cartilage isn’t life-threatening it does have huge quality of life implications for millions of people. Untreated cartilage damage can, over time lead to the degeneration of the joint, arthritis and chronic pain. Researchers at the University of Southern California (USC) were awarded $2.5 million to develop an off-the-shelf stem cell product that could be used to repair the damage.

The fourth and final award ($2.09 million) went to Ankasa Regenerative Therapeutics, which hopes to create a stem cell therapy for osteonecrosis. This is a painful, progressive disease caused by insufficient blood flow to the bones. Eventually the bones start to rot and die.

As Jonathan Thomas, Chair of the CIRM Board, said in a news release, we are hoping this is just the next step for these programs on their way to helping patients:

“These Translational Awards highlight our goal of creating a pipeline of projects, moving through different stages of research with an ultimate goal of a successful treatment. We are hopeful these projects will be able to use our newly created Stem Cell Center to speed up their progress and pave the way for approval by the FDA for a clinical trial in the next few years.”

A new and improved method for making healthy heart tissue is here

Scientists from the Gladstone Institutes have done it again. They’ve made a better and faster way of generating healthy heart tissue in mice with damaged hearts. With further advancements, their findings could potentially be translated into a new way of treating heart failure in patients.

Previously, the Gladstone team discovered that they could transform scar tissue in the damaged hearts of mice into healthy, beating heart muscle cells by a process called direct reprogramming. The team found that turning on three transcription factors, Gata4, Mef2c and Tbx5 (collectively called GMT), in the damaged hearts of mice activated heart genes that turned scar tissue cells, also known as cardiac fibroblasts, into beating heart cells or cardiomyocytes.

Their GMT direct cardiac reprogramming technology was only able to turn 10 percent of cardiac fibroblasts into cardiomyocytes in mice over the period of six to eight week. In their new CIRM-funded study published in Circulation, they improved upon their original reprogramming method by identifying two chemicals that improved the efficiency of making new heart cells. Not only were they able to create eight times the number of beating cardiomyocytes from mouse cardiac fibroblasts, but they were also able to speed up the reprogramming process to a period of just one week.

To find these chemicals, they screened a library of 5,500 small molecules. The chemicals that looked most promising for cardiac reprogramming were inhibitors of the TGF-β and WNT signaling pathways. The importance of these chemicals was explained in a Gladstone news release:

“The first chemical inhibits a growth factor that helps cells grow and divide and is important for repairing tissue after injury. The second chemical inhibits an important pathway that regulates heart development. By combining the two chemicals with GMT, the researchers successfully regenerated heart muscle and greatly improved heart function in mice that had suffered a heart attack.”

Senior author on the study, Deepak Srivastava, further explained:

“While our original process for direct cardiac reprogramming with GMT has been promising, it could be more efficient. With our screen, we discovered that chemically inhibiting two biological pathways active in embryonic formation improves the speed, quantity, and quality of the heart cells produced from our original process.”

Encouraged by their studies in mice, the scientists also tested their new and improved direct reprogramming method on human cells. Previously they found that while the same GMT transcription factors could reprogram human cardiac fibroblasts into cardiomyocytes, a combination of seven factors was required to make quality cardiomyocytes comparable to those seen in mice. But with the addition of the two inhibitors, they were able to reduce the number of reprogramming factors from seven to four, which included the GMT factors and one additional factor called Myocardin. These four factors plus the two chemical inhibitors were capable of reprograming human cardiac fibroblasts into beating heart cells.

With heart failure affecting more than 20 million people globally, the need for new therapies that can regenerate the heart is pressing. The Gladstone team is hoping to advance their research to a point where it could be tested in human patients with heart failure. First author on the study, Tamer Mohamed, concluded:

“Heart failure afflicts many people worldwide, and we still do not have an effective treatment for patients suffering from this disease. With our enhanced method of direct cardiac reprogramming, we hope to combine gene therapy with drugs to create better treatments for patients suffering from this devastating disease.”

Tamer Mohamed and Deepak Srivastava, Gladstone Institutes

Tamer Mohamed and Deepak Srivastava. Photo courtesy of Chris Goodfellow, Gladstone Institutes


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How research on a rare disease turned into a faster way to make stem cells

Forest Gump. (Paramount Pictures)

Forest Gump. (Paramount Pictures)

If Forest Gump were a scientist, I’d like to think he would have said his iconic line a little differently. Dr. Gump would have said, “scientific research is like a box of chocolates – you never know what you’re gonna get.”

A new CIRM-funded study coming out of the Gladstone Institutes certainly proves this point. Published yesterday in the Proceedings of the National Academy of Sciences, the study found that a specific genetic mutation known to cause a rare disease called fibrodysplasia ossificans progressiva (FOP) makes it easier to reprogram adult skin cells into induced pluripotent stem cells (iPSCs).

Shinya Yamanaka received the Nobel Prize in medicine in 2012 for his seminal discovery of the iPSC technology, which enabled scientists to generate patient specific pluripotent stem cell lines from adult cells like skin and blood. These iPSC lines are useful for modeling disease in a dish, identifying new therapeutic drugs, and potentially for clinical applications in patients. However, one of the rate-limiting steps to this technology is the inefficient process of making iPSCs.

Yamanaka, a senior investigator at Gladstone, knows this problem all too well. In a Gladstone news release he commented, “inefficiency in creating iPSCs is a major roadblock toward applying this technology to biomedicine. Our study identified a surprising way to increase the number of iPSCs that we can generate.”

So how did Yamanaka and his colleagues discover this new trick for making iPSCs more efficiently? Originally, their intentions were to model a rare genetic disease called FOP. It’s commonly known as “stone man syndrome” because the disease converts normal muscle and connective tissue into bone either spontaneously or spurred by injury. Bone growth begins at a young age starting at the neck and progressively moving down the body. Because there is no treatment or cure, patients typically have a lifespan of only 40 years.

The Gladstone team wanted to understand this rare disease better by modeling it in a dish using iPSCs generated from patients with FOP. These patients had a genetic mutation in the ACVR1 gene, which plays an important role in the development of the embryo. FOP patients have a mutant form of ACVR1 that overstimulates this developmental pathway and boosts the activity of a protein called BMP (bone morphogenic protein). When BMP signaling is ramped up, they discovered that they could produce significantly more iPSCs from the skin cells of FOP patients compared to normal, healthy skin cells.

First author on the study, Yohei Hayashi, explained their hypothesis for why this mutation makes it easier to generate iPSCs:

“Originally, we wanted to establish a disease model for FOP that might help us understand how specific gene mutations affect bone formation. We were surprised to learn that cells from patients with FOP reprogrammed much more efficiently than cells from healthy patients. We think this may be because the same pathway that causes bone cells to proliferate also helps stem cells to regenerate.”

To be sure that enhanced BMP signaling caused by the ACVR1 mutation was the key to generating more iPSCs, they blocked this signal and discovered that much fewer iPSCs were made from FOP patient skin cells.

Senior Investigator Bruce Conklin, who was a co-author on this study, succinctly summarized the importance of their findings:

“This is the first reported case showing that a naturally occurring genetic mutation improves the efficiency of iPSC generation. Creating iPSCs from patient cells carrying genetic mutations is not only useful for disease modeling, but can also offer new insights into the reprogramming process.”

Gladstone investigators Bruce Conklin and Shinya Yamanaka. (Photo courtesy of Chris Goodfellow, Gladstone Institutes)

Gladstone investigators Bruce Conklin and Shinya Yamanaka. (Photo courtesy of Chris Goodfellow, Gladstone Institutes)

From Pig Parts to Stem Cells: Scientist Douglas Melton Wins Ogawa-Yamanaka Prize for Work on Diabetes

Since the 1920s, insulin injections have remained the best solution for managing type 1 diabetes. Patients with this disease do not make enough insulin – a hormone that regulates the sugar levels in your blood – because the insulin-producing cells, or beta cells, in their pancreas are destroyed.

Back then, it took two tons of pig parts to make eight ounces of insulin, which was enough to treat 10,000 diabetic patients for six months. Biotech and pharmaceutical companies have since developed different types of human insulin treatments that include fast and long acting versions of the hormone. It’s estimated that $22 billion will be spent on developing insulin products for patients this year and that costs will rise to $32 billion in the year 2019.

These costs are necessary to keep insulin-dependent diabetes patients alive and healthy, but what if there was a different, potentially simpler solution to manage diabetes? One that looks to insulin-producing beta cells as the solution rather than daily hormone shots?

Douglas Melton Receives Stem Cell Prize for Work on Diabetes

Harvard scientist Douglas Melton envisions a world where one day, insulin-dependent diabetic patients are given stem cell transplants rather than shots to manage their diabetes. In the 90s, Melton’s son was diagnosed with type 1 diabetes. Motivated by his son’s diagnosis, Melton dedicated the focus of his research on understanding how beta cells develop from stem cells in the body and also in a cell culture dish.

Almost 30 years later, Melton has made huge strides towards understanding the biology of beta cell development and has generated methods to “reprogram” or coax pluripotent stem cells into human beta cells.

Melton was honored for his important contributions to stem cell and diabetes research at the second annual Ogawa-Yamanaka Stem Cell Prize ceremony last week at the Gladstone Institutes. This award recognizes outstanding scientists that are translating stem cell research from the lab to clinical trials in patients.

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Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease, explained why Melton was selected as this year’s prize winner:

Deepak Srivastava, Gladstone Institutes

Deepak Srivastava, Gladstone Institutes

“Doug’s research on genetic markers expressed during pancreas development have led to a reliable way to reprogram stem cells into human beta cells. His work provides the foundation for the ultimate goal of transplantable, patient-specific beta cells.”

 

Making Beta Cells for Patients

During the awards ceremony, Melton discussed his latest work on generating beta cells from human stem cells and how this technology could transform the way insulin-dependent patients are treated.

Douglas Melton, Harvard University.

Douglas Melton, Harvard University.

“I don’t mean to say that this [insulin treatment] isn’t a good idea. That’s keeping these people alive and in good health,” said Melton during his lecture. “What I want to talk about is a different approach. Rather than making more and better insulins and providing them by different medical devices, why not go back to nature’s solution which is the beta cells that makes the insulin?”

Melton first described his initial research on making pancreatic beta cells from embryonic and induced pluripotent stem cells in a culture dish. He described the power of this system for not only modeling diabetes, but also screening for potential drugs, and testing new therapies in animal models.

He also mentioned how he and his colleagues are developing methods to manufacture large amounts of human beta cells derived from pluripotent stem cells for use in patients. They are able to culture stem cells in large spinning flasks that accelerate the growth and development of pluripotent stem cells into billions of human beta cells.

Challenges and Future of Stem-Cell Derived Diabetes Treatments

Melton expressed a positive outlook for the future of stem cell-derived treatments for insulin-dependent diabetes, but he also mentioned two major challenges. The first is the need for better control over the methods that make beta cells from stem cells. These methods could be more efficient and generate higher numbers of beta cells (beta cells make up 16% of stem cell-derived cells using their current culturing methods). The second is preventing an autoimmune attack after transplanting the stem-cell derived beta cells into patients.

Melton and other scientists are already working on improving techniques to make more beta cells from stem cells. As for preventing transplanted beta cells from being attacked by the patient’s immune system, Melton described two possibilities: using an encapsulation device or biological protection to mask the transplanted cells from an attack.

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He mentioned a CIRM-funded clinical trial by ViaCyte, which is testing an encapsulation device that is placed under the skin. The device contains embryonic stem cell-derived pancreatic progenitor cells that develop into beta cells that secrete insulin into the blood stream. The device also prevents the immune system from attacking and killing the beta cells.

Melton also discussed a biological approach to protecting transplanted beta cells. In collaboration with Dan Anderson at MIT, they coated stem cell-derived beta cells in a biomaterial called alginate, which comes from seaweed. They injected alginate microcapsule-containing beta cells into diabetic mice and were able control their blood sugar levels.

At the end of his talk, Melton concluded that he believes that beta cell transplantation in an immunoprotective device containing stem cell-derived cells will have the most benefit for diabetes patients.

Gladstone Youtube video of Douglas Melton’s lecture at the Ogawa-Yamanaka Prize lecture.


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Multi-Talented Stem Cells: The Many Ways to Use Them in the Clinic

CIRM kicked off the 2016 International Society for Stem Cell Research (ISSCR) Conference in San Francisco with a public stem cell event yesterday that brought scientists, patients, patient advocates and members of the general public together to discuss the many ways stem cells are being used in the clinic to develop treatments for patients with unmet medical needs.

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, an Investigator at the Gladstone Institutes and UCSF Professor, moderated the panel of four scientists and three patient advocates. He immediately captured the audience’s attention by showing a stunning video of human heart cells, beating in synchrony in a petri dish. Conklin explained that scientists now have the skills and technology to generate human stem cell models of cardiomyopathy (heart disease) and many other diseases in a dish.

Conklin went on to highlight four main ways that stem cells are contributing to human therapy. First is using stem cells to model diseases whose causes are still largely unknown (like with Parkinson’s disease). Second, genome editing of stem cells is a new technology that has the potential to offer cures to patients with genetic disorders like sickle cell anemia. Third, stem cells are known to secrete healing factors, and transplanting them into humans could be beneficial. Lastly, stem cells can be engineered to attack cancer cells and overcome cancer’s normal way of evading the immune system.

Before introducing the other panelists, Conklin made the final point that stem cell models are powerful because scientists can use them to screen and develop new drugs for diseases that have no treatments or cures. His lab is already working on identifying new drugs for heart disease using human induced pluripotent stem cells derived from patients with cardiomyopathy.

Scientists and Patient Advocates Speak Out

Malin Parmar, Lund University

Malin Parmar, Lund University

The first scientist to speak was Malin Parmar, a Professor at Lund University. She discussed the history of stem cell development for clinical trials in Parkinson’s disease (PD). Her team is launching the first in-human trial for Parkinson’s using cells derived from human pluripotent stem cells in 2016. After Parmar’s talk, John Lipp, a PD patient advocate. He explained that while he might look normal standing in front of the crowd, his PD symptoms vary wildly throughout the day and make it hard for him to live a normal life. He believes in the work that scientists like Parmar are doing and confidently said, “In my lifetime, we will find a stem cell cure for Parkinson’s disease.”

Adrienne Shapiro, Patient Advocate

Adrienne Shapiro, Patient Advocate

The next scientist to speak was UCLA Professor Donald Kohn. He discussed his lab’s latest efforts to develop stem cell treatments for different blood disorder diseases. His team is using gene therapy to modify blood stem cells in bone marrow to treat and cure babies with SCID, also known as “bubble-boy disease”. Kohn also mentioned their work in sickle cell disease (SCD) and in chronic granulomatous disease, both of which are now in CIRM-funded clinical trials. He was followed by Adrienne Shapiro, a patient advocate and mother of a child with SCD. Adrienne gave a passionate and moving speech about her family history of SCD and her battle to help find a cure for her daughter. She said “nobody plans to be a patient advocate. It is a calling born of necessity and pain. I just wanted my daughter to outlive me.”

Henry Klassen (UC Irvine)

Henry Klassen, UC Irvine

Henry Klassen, a professor at UC Irvine, next spoke about blinding eye diseases, specifically retinitis pigmentosa (RP). This disease damages the photo receptors in the back of the eye and eventually causes blindness. There is no cure for RP, but Klassen and his team are testing the safety of transplanting human retinal progenitor cells in to the eyes of RP patients in a CIRM-funded Phase 1/2 clinical trial.

Kristen MacDonald, RP patient

Kristen MacDonald, RP patient

RP patient, Kristen MacDonald, was the trial’s first patient to be treated. She bravely spoke about her experience with losing her vision. She didn’t realize she was going blind until she had a series of accidents that left her with two broken arms. She had to reinvent herself both physically and emotionally, but now has hope that she might see again after participating in this clinical trial. She said that after the transplant she can now finally see light in her bad eye and her hope is that in her lifetime she can say, “One day, people used to go blind.”

Lastly, Catriona Jamieson, a professor and Alpha Stem Cell Clinic director at UCSD, discussed how she is trying to develop new treatments for blood cancers by eradicating cancer stem cells. Her team is conducting a Phase 1 CIRM-funded clinical trial that’s testing the safety of an antibody drug called Cirmtuzumab in patients with chronic lymphocytic leukemia (CLL).

Scientists and Patients need to work together

Don Kohn, Catriona Jamieson, Malin Parmar

Don Kohn, Catriona Jamieson, Malin Parmar

At the end of the night, the scientists and patient advocates took the stage to answer questions from the audience. A patient advocate in the audience asked, “How can we help scientists develop treatments for patients more quickly?”

The scientists responded that stem cell research needs more funding and that agencies like CIRM are making this possible. However, we need to keep the momentum going and to do that both the physicians, scientists and patient advocates need to work together to advocate for more support. The patient advocates in the panel couldn’t have agreed more and voiced their enthusiasm for working together with scientists and clinicians to make their hopes for cures a reality.

The CIRM public event was a huge success and brought in more than 150 people, many of whom stayed after the event to ask the panelists more questions. It was a great kick off for the ISSCR conference, which starts today. For coverage, you can follow the Stem Cellar Blog for updates on interesting stem cell stories that catch our eye.

CIRM Public Stem Cell Event

CIRM Public Stem Cell Event

A new way to make heart stem cells could potentially repair the damage of heart disease

Today we’re going to talk about heart failure. It’s a sobering topic given that over 20 million people world wide are currently suffering from this disease. Heart failure happens when the body’s heart can no longer pump blood effectively, which can lead to many nasty side effects and inevitably hastens death.

Typical strategies for treating heart failure focus on managing symptoms and delaying disease progression. But for patients, many of whom are elderly, a life of chronic management and frequent hospital stays is daunting. They deserve better.

Here’s where stem cell research could provide new treatments for heart failure. Some stem cells can be coaxed into new heart tissue that could repair damage and restore heart function. While other types of stem cells can release factors that facilitate the development of new blood vessels or that reduce tissue scarring, both of which improve heart function. Some of these treatments are being tested in clinical trials (for instance CIRM is funding a stem cell trial for heart disease sponsored by Capricor Therapeutics), although none have been approved yet.

But there’s good news on this front. Today, the Gladstone Institutes published a study in Cell Stem Cell describing a new method for making transplantable heart stem cells that improved heart function in mice and could potentially treat heart failure in humans.

A new method for making transplantable heart stem cells

The goal of the Gladstone study was to generate a specific type of heart stem cell called a cardiovascular progenitor cell that could survive and develop into the different types of mature heart cells to improve heart function when transplanted into mice.

Using technology previously developed in the lab of Gladstone Professor Sheng Ding, the team used a cocktail of chemicals to turn skin cells into cardiac progenitor cells (CPCs). These cells are like stem cells but specific to the heart and thus can only make heart cells. The CPCs they made had two important qualities: they could be expanded in a culture dish for multiple generations and they could develop into the three main types of adult heart cells (cardiomyocytes, endothelial cells and smooth muscle cells) that are required for heart regeneration.

Scientists made a new type of heart stem cell that can turn into the three main types of adult heart cells. (Image: Yu Zhang)

Gladstone scientists made a new type of heart stem cell that can make the three main types of adult heart cells. (Image: Yu Zhang)

Because of their ability to replicate and to become adult heart cells, they named these cells induced expandable cardiovascular progenitor cells or ieCPCs. They transplanted ieCPCs in mice that had suffered a heart attack and were pleased to see that 90% of engrafted cells (the ones that survived and stuck around) developed into functioning heart cells that worked seamlessly with the existing heart cells to improve the damaged heart’s ability to pump blood. From a single injection of one million ieCPCs, the improvements in heart function lasted for three months.

In a Gladstone News Release, first author on the study, Yu Zhang, explained why ieCPCs are better for transplantation into damaged hearts than adult heart cells like cardiomyocytes or the muscle cells of the heart:

“Scientists have tried for decades to treat heart failure by transplanting adult heart cells, but these cells cannot reproduce themselves, and so they do not survive in the damaged heart. Our generated ieCPCs can prolifically replicate and reliably mature into the three types of cells in the heart, which makes them a very promising potential treatment for heart failure.”

Another benefit to ieCPCs was that they did not generate tumors when transplanted. This can happen with non-heart stem cells or with cells derived from pluripotent stem cells.

What does the future hold for ieCPCs?

A heart attack can kill more than one billion heart cells, and while the heart has some regenerative ability, it cannot replace that many cells on its own. The Gladstone study is exciting because it provides a new population of heart stem cells that can be expanded in a dish to generate a large donor population of stem cells for transplantation.

Senior author Shen Ding spoke to the robustness of their new stem cell technology:

Sheng Ding

Sheng Ding

“Cardiac progenitor cells could be ideal for heart regeneration. They are the closest precursor to functional heart cells, and, in a single step, they can rapidly and efficiently become heart cells, both in a dish and in a live heart. With our new technology, we can quickly create billions of these cells in a dish and then transplant them into damaged hearts to treat heart failure.”

Additionally, their new method opens the doors for generating patient-specific stem cell treatments.

“Because these cells are generated from skin cells, it opens the door for personalized medicine, using a patient’s own cells to treat their disease.”

Sheng Ding’s lab is one to watch if you follow research in stem cell biology and regenerative medicine. We recently blogged about a different but equally important study from his lab where he made functional pancreatic beta cells from skin as a potential cell therapy for diabetes. I hope that his team will ultimately be able to translate their current research in both diabetes and heart disease towards clinical applications in humans.

Growing Stem Cell Research in California (Video)

How a Gladstone scientist is using bioengineering to push the pace of stem cell research

At CIRM, we strive to fund the most promising stem cell research and speed the advancement of stem cell treatments to patients who need them. Because we are a state agency, we generally focus on funding scientists, universities, and companies located in California. But we recognize that high quality stem cell research is ongoing throughout the country. That’s why CIRM has programs that fund research originating outside California and that recruit talented stem cell scientists to join our state’s vibrant stem cell community.

Today we want to share a video we produced titled, “Growing Stem Cell Research in California” that provides an example of how CIRM has catalyzed the growth of stem cell research by helping recruit Dr. Todd McDevitt, a leading biomedical engineer in stem cell research, to the Gladstone Institutes in San Francisco.

Todd started his lab at the Georgia Institute of Technology in Atlanta and moved to the Gladstone a year ago to conduct research using human pluripotent stem cells to engineer 3D micro-tissues for use in drug development and disease modeling. His move was made possible by a CIRM Research Leadership Award, which allowed the Gladstone to recruit Todd and is now his lab’s major source of funding.

Todd McDevitt, Gladstone Institutes

Todd McDevitt, Gladstone Institutes

With an expertise in tissue engineering, Todd and his team are collaborating with other researchers at the Gladstone on projects that use human stem cells to create organ-like tissues to advance research and therapeutic development for a wide range of areas including brain disease, heart disease and spinal cord injury.

Todd is a young and talented scientist who is using his expertise in bioengineering to push the pace of stem cell research ultimately, we hope, to improve human health. You can read more about Todd’s first year anniversary at the Gladstone in their latest news release.