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.

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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.

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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:

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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.”

 

 

 

 

 

 

 

 

 

Stories that caught our eye: color me stem cells, delivering cell therapy with nanomagnets, and stem cell decisions

Nanomagnets: the future of targeted stem cell therapies? Your blood vessels are made up of tightly-packed endothelial cells. This barrier poses some big challenges for the delivery of drugs via the blood. While small molecules are able make their way through the small gaps in the blood vessel walls, larger drug molecules, including proteins and cells, are not able to penetrate the vessel to get therapies to diseased areas.

This week, researchers at Rice University report in Nature Communications on an ingenious technique using tiny magnets that may overcome this drug delivery problem.

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At left, the nanoparticles are evenly distributed among the microtubules that help give the cells their shape. At right, after a magnetic field is applied, the nanoparticles are pulled toward one end of the cells and change their shapes. Credit: Laboratory of Biomolecular Engineering and Nanomedicine/Rice University

Initial studies showed that adding magnetic nanoparticles to the endothelial cells and then applying a magnetic field affected the cells’ internal scaffolding, called microtubules. These structures are responsible for maintaining the tight cell to cell connections. The team took the studies a step further by growing the cells in specialized petri dishes containing tiny, tube-shaped channels. Applying a magnetic field to the cells caused the cell-cell junctions to form gaps, making the blood vessel structures leaky. Simply turning off the magnetic field closed up the gaps within a few hours.

Though a lot of research remains, the team aims to apply this on-demand induction of cell leakiness along with adding the magnetic nanoparticles to stem cell therapy products to help target the treatment to specific area. In a press release, team leader Dr. Gang Bao spoke about possible applications to arthritis therapy:

“The problem is how to accumulate therapeutic stem cells around the knee and keep them there. After injecting the nanoparticle-infused cells, we want to put an array of magnets around the knee to attract them.”

To differentiate or not differentiate: new insights During the body’s development, stem cells must differentiate, or specialize, into functional cells – like liver, heart, brain. But once that specialization occurs, the cells lose their pluripotency, or the ability to become any type of cell. So, stem cells must balance the need to differentiate with the need to make copies of itself to maintain an adequate supply of stem cells to complete the development process. And even after a fully formed baby is born, it’s still critical for adult stem cells to balance the need to regenerate damaged tissue versus stashing away a pool of stem cells in various organs for future regeneration and replacement of damaged or diseased tissues.

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Visualizing activation of Nanog gene activity (bright green spot) within cell nucleus. 
Image: Courtesy of Bony De Kumar, Ph.D., and Robb Krumlauf, Ph.D., Stowers Institute for Medical Research

A report this week in the Proceedings of the National Academy of Sciences finds evidence that the two separate processes – differentiation and pluripotency – directly communicate with each other as way to ensure a proper balance between the two states.

The study, carried out by researchers at Stowers Institute for Medical Research in Kansas City, Missouri, focused on the regulation of two genes: Nanog and Hox. Nanog is critical for maintaining a stem cell’s ability to become a specialized cell type. In fact, it’s one of the four genes initially used to reprogram adult cells back into induced pluripotent stem cells. The Hox gene family is responsible for generating a blueprint of the body plan in a developing embryo. Basically, the pattern of Hox gene activity helps generate the body plan, basically predetermining where the various body parts and organs will form.

Now, both Nanog and Hox proteins act by binding to DNA and turning on a cascade of other genes that ultimately maintain pluripotency or promote differentiation. By examining these other genes, the researchers were surprised to find that both Nanog and Hox were bound to both the pluripotency and differentiation genes. They also found that Nanog and Hox can directly inhibit each other. Taken together, these results suggest that exquisite control of both processes occurs cross regulation of gene activity.

Dr. Robb Krumlauf one of authors on the paper talked about the significance of the result in a press release:

“Over the past 10 to 20 years, biologists have shown that cells are actively assessing their environment, and that they have many fates they can choose. The regulatory loops we’ve found show how the dynamic nature of cells is being maintained.”

Color me stem cells Looking to improve your life and the life of those around you? Then we highly recommend you pay a visit to today’s issue of Right Turn, a regular Friday feature of  Signals, the official blog of CCRM, Canada’s public-private consortium supporting the development of regenerative medicine technologies.

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Collage sample of CCRM’s new coloring sheets. Image: copyright CCRM 2017

As part of an public outreach effort they have created four new coloring sheets that depict stem cells among other sciency topics. They’ve set up a DropBox link to download the pictures so you can get started right away.

Adult coloring has swept the nation as the hippest new pastime. And it’s not just a frivolous activity, as coloring has been shown to have many healthy benefits like reducing stressed and increasing creativity. Just watch any kid who colors. In fact, share these sheet with them, it’s intended for children too.

Stem cell stories that caught our eye: new baldness treatments?, novel lung stem cells, and giraffe stem cells

Novel immune system/stem cell interaction may lead to better treatments for baldness. When one thinks of the immune system it’s usually in terms of the body’s ability to fight off a bad cold or flu virus. But a team of UCSF researchers this week report in Cell that a particular cell of the immune system is key to instructing stem cells to maintain hair growth. Their results suggest that the loss of these immune cells, called regulatory T cells (Tregs for short), may be the cause of baldness seen in alopecia areata, a common autoimmune disorder and may even play a role in male pattern baldness.

Alopecia, a common autoimmune disorder that causes baldness. Image: Shutterstock

While most cells of the immune system recognize and kill foreign or dysfunctional cells in our bodies, Tregs act to subdue those cells to avoid collateral damage to perfectly healthy cells. If Tregs become impaired, it can lead to autoimmune disorders in which the body attacks itself.

The UCSF team had previously shown that Tregs allow microorganisms that are beneficial to skin health in mice to avoid the grasp of the immune system. In follow up studies they intended to examine what happens to skin health when Treg cells were inhibited in the skin of the mice. The procedure required shaving away small patches of hair to allow observation of the skin. Over the course of the experiment, the scientists notice something very curious. Team lead Dr. Michael Rosenblum recalled what they saw in a UCSF press release:

“We quickly noticed that the shaved patches of hair never grew back, and we thought, ‘Hmm, now that’s interesting. We realized we had to delve into this further.”

That delving showed that Tregs are located next to hair follicle stem cells. And during the hair growth, the Tregs grow in number and surround the stem cells. Further examination, found that Tregs trigger the stem cells through direct cell to cell interactions. These mechanisms are different than those used for their immune system-inhibiting function.

With these new insights, Dr. Rosenblum hopes this new-found role for Tregs in hair growth may lead to better treatments for Alopecia, one of the most common forms of autoimmune disease.

Novel lung stem cells bring new insights into poorly understood chronic lung disease. Pulmonary fibrosis is a chronic lung disease that’s characterized by scarring and changes in the structure of tiny blood vessels, or microvessels, within lungs. This so-called “remodeling” of lung tissue hampers the transfer of oxygen from the lung to the blood leading to dangerous symptoms like shortness of breath. Unfortunately, the cause of most cases of pulmonary fibrosis is not understood.

This week, Vanderbilt University Medical Center researchers report in the Journal of Clinical Investigation the identification of a new type of lung stem cell that may play a role in lung remodeling.

Susan Majka and Christa Gaskill, and colleagues are studying certain lung stem cells that likely contribute to the pathobiology of chronic lung diseases.  Photo by: Susan Urmy

Up until now, the cells that make up the microvessels were thought to contribute to the detrimental changes to lung tissue in pulmonary fibrosis or other chronic lung diseases. But the Vanderbilt team wasn’t convinced since these microvessel cells were already fully matured and wouldn’t have the ability to carry out the lung remodeling functions.

They had previously isolated stem cells from both mouse and human lung tissue located near microvessels. In this study, they tracked these mesenchymal progenitor cells (MPCs) in normal and disease inducing scenarios. The team’s leader, Dr. Susan Majka, summarized the results of this part of the study in a press release:

“When these cells are abnormal, animals develop vasculopathy — a loss of structure in the microvessels and subsequently the lung. They lose the surfaces for gas exchange.”

The team went on to find differences in gene activity in MPCs from healthy versus diseased lungs. They hope to exploit these differences to identify molecules that would provide early warnings of the disease. Dr. Majka explains the importance of these “biomarkers”:

“With pulmonary vascular diseases, by the time a patient has symptoms, there’s already major damage to the microvasculature. Using new biomarkers to detect the disease before symptoms arise would allow for earlier treatment, which could be effective at decreasing progression or even reversing the disease process.”

The happy stem cell story of Mahali the giraffe. We leave you this week with a feel-good story about Mahali, a 14-year old giraffe at the Cheyenne Mountain Zoo in Colorado. Mahali had suffered from chronic arthritis in his front left leg. As a result, he could not move well and was kept isolated from his herd.

Giraffes at Cheyenne Mountain Zoo. Photo: Denver Post

The zoo’s head veterinarian, Dr. Liza Dadone, decided to try a stem cell therapy procedure to bring Mahali some relief and a better quality of life. It’s the first time such a treatment would be performed on a giraffe. With the help of doctors at Colorado State University’s James L. Voss Veterinary Teaching Hospital, 100 million stem cells grown from Mahali’s blood were injected into his arthritic leg.

Before treatment, thermograph shows inflammation (red/yellow) in Mahali’s left front foot (seen at far right of each image); after treatment inflammation resolved (blue/green). Photos: Cheyenne Mountain Zoo

In a written statement to the Colorado Gazette, Dr. Dadone summarized the positive outcome:

“Prior to the procedure, he was favoring his left front leg and would lift that foot off the ground almost once per minute. Since then, Mahali is no longer constantly lifting his left front leg off the ground and has resumed cooperating for hoof care. A few weeks ago, he returned to life with his herd, including yard access. On the thermogram, the marked inflammation up the leg has mostly resolved.”

Now, Dr. Dadone made sure to state that other treatments and medicine were given to Mahali in addition to the stem cell therapy. So, it’s not totally clear to what extent the stem cells contributed to Mahali’s recovery. Maybe future patients will receive stem cells alone to be sure. But for now, we’re just happy for Mahali’s new lease on life.

Stem cell stories that caught our eye: lab-grown blood stem cells and puffer fish have the same teeth stem cells as humans

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Scientists finally grow blood stem cells in the lab!

Two exciting stem cell studies broke through the politics-dominated headlines this week. Both studies, published in the journal Nature, demonstrated that human hematopoietic or blood stem cells can be grown in the lab.

This news is a big deal because scientists have yet to make bonafide blood stem cells from pluripotent stem cells or other human cells. These stem cells not only create all the cells in our blood and immune systems, but also can be used to develop therapies for patients with blood cancers and genetic blood disorders.

But to do these experiments, you need a substantial source of blood stem cells – something that has eluded scientists for decades. That’s where these two studies come to the rescue. One study was spearheaded by George Daley at the Boston Children’s Hospital in Massachusetts and the other was led by Shahin Rafii at the Weill Cornell Medical College in New York City.

Researchers have made blood stem cells and progenitor cells from pluripotent stem cells. Credit: Steve Gschmeissner Getty Images

George Daley and his team developed a strategy that matured human induced pluripotent stem cells (iPS cells) into blood-forming stem and progenitor cells. It’s a two-step process that first uses a cocktail of chemicals to make hemogenic endothelium, the embryonic tissue that generates blood stem cells. The second step involved treating these intermediate cells with a combination of seven transcription factors that directed them towards a blood stem cell fate.

These modified human blood stem cells were then transplanted into mice where they developed into blood stem cells that produced blood and immune cells. First author on the study, Ryohichi Sugimura, explained the applications that their technology could be used for in a Boston Children’s Hospital news release,

“This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells. This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions.”

The second study by Shahin Rafii and his team at Cornell used a different strategy to generate blood-forming stem cells. Instead of genetically manipulating iPS cells, they selected a more mature cell type to directly reprogram into blood stem cells. Using four transcription factors, they successfully reprogrammed mouse endothelial cells, which line the insides of blood vessels, into blood-forming stem cells that repopulated the blood and immune systems of irradiated mice.

Raffii believe his method is simpler and more efficient than Daley’s. In coverage by Nature News, he commented,

“Using the most efficient method to generate stem cells matters because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumors if they are implanted into people.”

To play devil’s advocate, Daley’s technique might appeal more to some because the starting source of iPS cells is much easier to obtain and culture in the lab than endothelial cells that have to be extracted from the blood vessels of animals or people. Furthermore, Daley argued that his team’s method could “be made more efficient, and [is] less likely to spur tumor growth and other abnormalities in modified cells.”

The Nature News article compares the achievements of both studies and concluded,

“Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS cells.”

 

Humans and puffer fish have the same tooth-making stem cells.

Here’s a fun fact for your next blind date: humans and puffer fish share the same genes that are responsible for making teeth. Scientists from the University of Sheffield in England discovered that the stem cells that make teeth in puffer fish are the same stem cells that make the pearly whites in humans. Their work was published in the journal PNAS earlier this week.

Puffer fish. Photo by pingpogz on Flickr.

But if you look at this puffer fish, you’ll see a dramatic difference between its smile and ours – their teeth look more like a beak. Research has shown that the tooth-forming stem cells in puffer fish produce tooth plates that form a beak-like structure, which helps them crush and consume their prey.

So why is this shared evolution between humans and puffer fish important when our teeth look and function so differently? The scientists behind this research believe that studying the pufferfish could unearth answers about tooth loss in humans. The lead author on the study, Dr. Gareth Fraser, concluded in coverage by Phys.org,

“Our study questioned how pufferfish make a beak and now we’ve discovered the stem cells responsible and the genes that govern this process of continuous regeneration. These are also involved in general vertebrate tooth regeneration, including in humans. The fact that all vertebrates regenerate their teeth in the same way with a set of conserved stem cells means that we can use these studies in more obscure fishes to provide clues to how we can address questions of tooth loss in humans.”

Stem cell stories that caught our eye: better ovarian cancer drugs, creating inner ear tissue, small fish big splash

Two drugs are better than one for ovarian cancer (Karen Ring). Earlier this week, scientists from UCLA reported that a combination drug therapy could be an effective treatment for 50% of aggressive ovarian cancers. The study was published in the journal Precision Oncology and was led by Dr. Sanaz Memarzadeh.

Women with high-grade ovarian tumors have an 85% chance of tumor recurrence after treatment with a common chemotherapy drug called carboplatin. The UCLA team found in a previous study that ovarian cancer stem cells are to blame because they are resistant to carboplatin. It’s because these stem cells have an abundance of proteins called cIAPs, which prevent cell death from chemotherapy.

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Ovarian cancer cells (blue) expressing cIAP protein (red) on the left are more sensitive to a combination therapy than cancer cells that don’t express the protein on the right. (UCLA Broad Stem Cell Research Center/Precision Oncology)

Memarzadeh discovered that an experimental drug called birinapant made some ovarian cancer tumors more sensitive to chemotherapy treatment by breaking down cIAPs. This gave her the idea that combining the two drugs, birinapant and carboplatin, might be a more effective strategy for treating aggressive ovarian tumors.

By treating with the two drugs simultaneously, the scientists improved the survival rate of mice with ovarian cancer. They also tested this combo drug treatment on 23 ovarian cancer cell lines derived from women with highly aggressive tumors. The treatment killed off half of the cell lines indicating that some forms of this cancer are resistant to the combination treatment.

When they measured the levels of cIAPs in the human ovarian cancer cell lines, they found that high levels of the proteins were associated with ovarian tumor cells that responded well to the combination treatment. This is exciting because it means that clinicians can analyze tumor biopsies for cIAP levels to determine whether certain ovarian tumors would respond well to combination therapy.

Memarzadeh shared her plans for future research in a UCLA news release,

“I believe that our research potentially points to a new treatment option. In the near future, I hope to initiate a phase 1/2 clinical trial for women with ovarian cancer tumors predicted to benefit from this combination therapy.”

In a first, researchers create inner ear tissue. From heart muscle to brain cells to insulin-producing cells, researchers have figured out how to make a long list of different human cell types using induced pluripotent stem cells (iPSCs) – cells taken from the body and reprogrammed into a stem cell-like state.

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Human inner ear organoid with sensory hair cells (cyan) and sensory neurons (yellow). An antibody for the protein CTBP2 reveals cell nuclei as well as synapses between hair cells and neurons (magenta). | Photo: Karl Koehler

This week, a research group at the Indiana University School of Medicine successfully added inner ear cells to that list. This feat, published in Nature Biotechnology, is especially important given the fact that the inner ear is one of the few parts of the body that cannot be biopsied for further examination. With these cells in hands, new insights into the causes of hearing loss and balance disorders may be on the horizon.

The inner ear contains 75,000 sensory hair cells that convert sound waves into electrical signals to the brain. Loud noises, drug toxicity, and genetic mutations can permanently damage the hair cells leading to hearing loss and dizziness. Over 15%  of the U.S. population have some form of hearing loss and that number swells to 67% for people over 75.

Due to the complex shape of the inner ear, the team grew the iPSCs into three dimensional balls of cells rather than growing them as a flat layer of cells on a petri dish. With educated guesses sprinkled in with some trial and error, the scientists, for the time, identified a recipe of proteins that stimulated the iPSCs to transform into inner ear tissue. And like any great recipe, it wasn’t so much the ingredient list but the timing that was key:

“If you apply these signals at the wrong time you can potentially generate a brain instead of an inner ear,” first author Dr. Karl Koehler said in an interview with Gizmodo. “The real breakthrough is that we figured out the exact timing to do each one of these [protein] treatments.”

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Senior author, Eri Hashino, Ph.D., and first author, Karl R. Koehler, Ph.D. Photo: Indiana University

Careful examination shows that the tissue, referred to as organoids, not only contained the sensory hair cells of the inner ear cell but also nerve cells, or neurons, that are responsible for relaying the sound waves to the brain. Koehler explained the importance of this result in a press release:

“We also found neurons, like those that transmit signals from the ear to the brain, forming connections with sensory cells. This is an exciting feature of these organoids because both cell types are critical for proper hearing and balance.”

Though it’s still early days, these iPSC-derived inner ear organoids are a key step toward the ultimate goal of repairing hearing loss. Senior author, Dr. Eri Hashino, talked about the team’s approach to reach that goal:

“Up until now, potential drugs or therapies have been tested on animal cells, which often behave differently from human cells. We hope to discover new drugs capable of helping regenerate the sound-sending hair cells in the inner ear of those who have severe hearing problems.”

This man’s research is no fish tale
And finally, we leave you this week with a cool article and video by STAT. It features Dr. Leonard Zon of Harvard University and his many, many tanks full of zebrafish. This little fish has made a huge splash in understanding human development and disease. But don’t take my word for it, watch the video!

Stem cell stories that caught our eye: spinal cord injury trial keeps pace; SMART cells make cartilage and drugs

CIRM-funded spinal cord injury trial keeping a steady pace

Taking an idea for a stem cell treatment and developing it into a Food and Drug Administration-approved cell therapy is like running the Boston Marathon because it requires incremental progress rather than a quick sprint. Asterias Biotherapeutics continues to keep a steady pace and to hit the proper milestones in its race to develop a stem cell-based treatment for acute spinal cord injury.


Just this week in fact, the company announced an important safety milestone for its CIRM-funded SciStar clinical trial. This trial is testing the safety and effectiveness of AST-OPC1, a human embryonic stem cell-derived cell therapy that aims to regenerate some of the lost movement and feeling resulting from spinal cord injuries to the neck.

Periodically, an independent safety review board called the Data Monitoring Committee (DMC) reviews the clinical trial data to make sure the treatment is safe in patients. That’s exactly what the DMC concluded as its latest review. They recommended that treatments with 10 and 20 million cell doses should continue as planned with newly enrolled clinical trial participants.

About a month ago, Asterias reported that six of the six participants who had received a 10 million cell dose – which is transplanted directly into the spinal cord at the site of injury – have shown improvement in arm, hand and finger function nine months after the treatment. These outcomes are better than what would be expected by spontaneous recovery often observed in patients without stem cell treatment. So, we’re hopeful for further good news later this year when Asterias expects to provide more safety and efficacy data on participants given the 10 million cell dose as well as the 20 million cell dose.

It’s a two-fer: SMART cells that make cartilage and release anti-inflammation drug
“It’s a floor wax!”….“No, it’s a dessert topping!”
“Hey, hey calm down you two. New Shimmer is a floor wax and a dessert topping!”

Those are a few lines from the classic Saturday Night Live skit that I was reminded of when reading about research published yesterday in Stem Cell Reports. The clever study generated stem cells that not only specialize into cartilage tissue that could help repair arthritic joints but the cells also act as a drug dispenser that triggers the release of a protein that dampens inflammation.

Using CRISPR technology, a team of researchers led by Farshid Guilak, PhD, at Washington University School of Medicine in St. Louis, rewired stem cells’ genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter inflammation. The technique eventually could act as a vaccine for arthritis and other chronic conditions. Image: ELLA MARUSHCHENKO

The cells were devised by a research team at Washington University School of Medicine in St. Louis. They started out with skin cells collected from the tails of mice. Using the induced pluripotent stem cell technique, the skin cells were reprogrammed into an embryonic stem cell-like state. Then came the ingenious steps. The team used the CRISPR gene-editing method to create a negative feedback loop in the cells’ inflammation response. They removed a gene that is activated by the potent inflammatory protein, TNF-alpha and replaced it with a gene that blocks TNF-alpha. Analogous experiments were carried out with another protein called IL-1.

Rheumatoid arthritis often affects the small joints causing painful swelling and disfigurement. Image: Wikipedia

Now, TNF-alpha plays a key role in triggering inflammation in arthritic joints. But this engineered cell, in the presence of TNF-alpha, activates the production of a protein that inhibits the actions of TNF-alpha. Then the team converted these stem cells into cartilage tissue and they went on to show that the cartilage was indeed resistant to inflammation. Pretty smart, huh? In fact, the researchers called them SMART cells for “Stem cells Modified for Autonomous Regenerative Therapy.” First author Dr. Jonathan Brunger summed up the approach succinctly in a press release:

“We hijacked an inflammatory pathway to create cells that produced a protective drug.”

This type of targeted treatment of arthritis would have a huge advantage over current anti-TNF-alpha therapies. Arthritis drugs like Enbrel, Humira and Remicade are very effective but they block the immune response throughout the body which carries an increased risk for serious infections and even cancer.

The team is now testing the cells in animal models of rheumatoid arthritis as well as other inflammation disorders. Those results will be important to determine whether or not this approach can work in a living animal. But senior Dr. Farshid Guilak also has an eye on future applications of SMART cells:

“We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, it’s possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.”

Stem Cell Stories That Caught Our Eye: Plasticity in the pancreas and two cool stem cell tools added to the research toolbox

There’s more plasticity in the pancreas than we thought. You’re taught a lot of things about the world when you’re young. As you get older, you realize that not everything you’re told holds true and it’s your own responsibility to determine fact from fiction. This evolution in understanding happens in science too. Scientists do research that leads them to believe that biological processes happen a certain way, only to sometimes find, a few years later, that things are different or not exactly what they had originally thought.

There’s a great example of this in a study published this week in Cell Metabolism about the pancreas. Scientists from UC Davis found that the pancreas, which secretes a hormone called insulin that helps regulate the levels of sugar in your blood, has more “plasticity” than was originally believed. In this case, plasticity refers to the ability of a tissue or organ to regenerate itself by replacing lost or damaged cells.

The long-standing belief in this field was that the insulin producing cells, called beta cells, are replenished when beta cells actively divide to create more copies of themselves. In patients with type 1 diabetes, these cells are specifically targeted and killed off by the immune system. As a result, the beta cell population is dramatically reduced, and patients have to go on life-long insulin treatment.

UC Davis researchers have identified another type of insulin-producing cell in the islets, which appears to be an immature beta cell shown in red. (UC Davis)

But it turns out there is another cell type in the pancreas that is capable of making beta cells and they look like a teenage, less mature version of beta cells. The UC Davis team identified these cells in mice and in samples of human pancreas tissue. These cells hangout at the edges of structures called islets, which are clusters of beta cells within the pancreas. Upon further inspection, the scientists found that these immature beta cells can secrete insulin but cannot detect blood glucose like mature beta cells. They also found their point of origin: the immature beta cells developed from another type of pancreatic cell called the alpha cell.

Diagram of immature beta cells from Cell Metabolism.

In coverage by EurekAlert, Dr Andrew Rakeman, the director of discovery research at the Juvenile Diabetes Research Foundation, commented on the importance of this study’s findings and how it could be translated into a new approach for treating type 1 diabetes patients:

“The concept of harnessing the plasticity in the islet to regenerate beta cells has emerged as an intriguing possibility in recent years. The work from Dr. Huising and his team is showing us not only the degree of plasticity in islet cells, but the paths these cells take when changing identity. Adding to that the observations that the same processes appear to be occurring in human islets raises the possibility that these mechanistic insights may be able to be turned into therapeutic approaches for treating diabetes.”

 

Say hello to iPSCORE, new and improved tools for stem cell research. Stem cells are powerful tools to model human disease and their power got a significant boost this week from a new study published in Stem Cell Reports, led by scientists at UC San Diego School of Medicine.

The team developed a collection of over 200 induced pluripotent stem cell (iPS cell) lines derived from people of diverse ethnic backgrounds. They call this stem cell tool kit “iPSCORE”, which stands for iPSC Collection for Omic Research (omics refers to a field of study in biology ending in -omics, such as genomics or proteomics). The goal of iPSCORE is to identify particular genetic variants (unique differences in DNA sequence between people’s genomes) that are associated with specific diseases and to understand why they cause disease at the molecular level.

In an interview with Phys.org, lead scientist on the study, Dr. Kelly Frazer, further explained the power of iPSCORE:

“The iPSCORE collection contains 75 lines from people of non-European ancestry, including East Asian, South Asian, African American, Mexican American, and Multiracial. It includes multigenerational families and monozygotic twins. This collection will enable us to study how genetic variation influences traits, both at a molecular and physiological level, in appropriate human cell types, such as heart muscle cells. It will help researchers investigate not only common but also rare, and even family-specific variations.”

This research is a great example of scientists identifying a limitation in stem cell research and expanding the stem cell tool kit to model diseases in a diverse human population.

A false color scanning electron micrograph of cultured human neuron from induced pluripotent stem cell. Credit: Mark Ellisman and Thomas Deerinck, UC San Diego.

Stem cells that can grow into ANY type of tissue. Embryonic stem cells can develop into any cell type in the body, earning them the classification of pluripotent. But there is one type of tissue that embryonic stem cells can’t make and it’s called extra-embryonic tissue. This tissue forms the supportive tissue like the placenta that allows an embryo to develop into a healthy baby in the womb.

Stem cells that can develop into both extra-embryonic and embryonic tissue are called totipotent, and they are extremely hard to isolate and study in the lab because scientists lack the methods to maintain them in their totipotent state. Having the ability to study these special stem cells will allow scientists to answer questions about early embryonic development and fertility issues in women.

Reporting this week in the journal Cell, scientists from the Salk Institute in San Diego and Peking University in China identified a cocktail of chemicals that can stabilize human stem cells in a totipotent state where they can give rise to either tissue type. They called these more primitive stem cells extended pluripotent stem cells or EPS cells.

Salk Professor Juan Carlos Izpisua Bemonte, co–senior author of the paper, explained the problem their study addressed and the solution it revealed in a Salk news release:

“During embryonic development, both the fertilized egg and its initial cells are considered totipotent, as they can give rise to all embryonic and extra-embryonic lineages. However, the capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology. This is the first study reporting the derivation of a stable stem cell type that shows totipotent-like bi-developmental potential towards both embryonic and extra-embryonic lineages.”

Human EPS cells (green) can be detected in both the embryonic part (left) and extra-embryonic parts (placenta and yolk sac, right) of a mouse embryo. (Salk Institute)

Using this new method, the scientists discovered that human EPS stem cells were able to develop chimeric embryos with mouse stem cells more easily than regular embryonic stem cells. First author on the study, Jun Wu, explained why this ability is important:

“The superior chimeric competency of both human and mouse EPS cells is advantageous in applications such as the generation of transgenic animal models and the production of replacement organs. We are now testing to see whether human EPS cells are more efficient in chimeric contribution to pigs, whose organ size and physiology are closer to humans.”

The Salk team reported on advancements in generating interspecies chimeras earlier this year. In one study, they were able to grow rat organs – including the pancreas, heart and eyes – in a mouse. In another study, they grew human tissue in early-stage pig and cattle embryos with the goal of eventually developing ways to generate transplantable organs for humans. You can read more about their research in this Salk news release.

Stem cell stories that caught our eye: menstrual cycle on a chip, iPS cells from urine, Alpha Stem Cell Clinic Symposium videos

Say hello to EVATAR, a mini female reproductive system on a 3D chip. (Karen Ring)
I was listening to the radio this week in my car and caught snippets of a conversation that mentioned the word “Evatar”. Having tuned in halfway through the story, naturally I thought that the reporters were talking about James Cameron’s sequel to Avatar, and was slightly puzzled about the early press since the sequel isn’t expected to come out until 2020.

I was wrong in my assumption, but not that far off. It turns out that they were actually talking about a cutting edge new technology that generates artificial organs on 3D microfluidic chips. In the case of EVATAR, scientists have developed a functioning mini female reproductive system with all the essential components to recreate the female menstrual cycle. This sounds like science fiction, but it’s real. If you don’t believe me, you can read the publication in the journal Nature Communications.

EVATAR is a 3D organ-on-a-chip representing the female reproductive system. (Photo credit: Woodruff Lab, Northwestern University.)

 The chip consists of small boxes that each house an essential component of the reproductive system including the uterus, fallopian tubes, ovaries, cervix, and vagina. These tissues are generated from human stem cells except for the ovaries which were derived from mouse stem cells. The mini organs are connected to each other by tiny tubes and pumps that simulate blood flow and create a complete reproductive system. By adding specific hormones to this chip, the scientists stimulated the ovaries to produce the hormones estrogen and progesterone and even release an egg.

With EVATAR up and running, scientists are planning to use these personalized devices for various medical purposes including understanding reproductive diseases like endometriosis and testing how drugs affect specific people. The team is also developing a male version of this 3D reproductive chip called ADATAR and plans to study the two models side by side to understand differences in drug metabolism between men and women.

EVATAR is part of a larger project spearheaded by the National Institutes of Health to develop a “body-on-a-chip”. The lead author on the study, Teresa Woodruff from Northwestern University, explained in a news release how scaling down a human body to the size of a small chip that fits in your hand scales up the impact that the technology can have on developing personalized medicine for patients with various diseases.

“If I had your stem cells and created a heart, liver, lung and an ovary, I could test 10 different drugs at 10 different doses on you and say, ‘Here’s the drug that will help your Alzheimer’s or Parkinson’s or diabetes. It’s the ultimate personalized medicine, a model of your body for testing drugs.”

EVATAR has been popular in the press and was picked up by news outlets like NPR, STAT news and Tech Times. You can learn more about this technology by watching the video below provided by Northwestern Medicine.

Abracadabra: Researchers make stem cells from urine (Todd Dubnicoff)
I think one of the reasons the induced pluripotent stem cell (iPSC) technique became a Nobel Prize winning breakthrough, is due to its simplicity. All it takes is a slightly invasive skin biopsy and the addition of a few key factors to reprogram the skin cells into an embryonic stem cell-like state. The method is a game-changer for studying brain development disorders like Down Syndrome. Brain cells from affected individuals are not accessible so deriving these cells from iPSCs is critical in examining the differences between a healthy and Down Syndrome brain.

But skin biopsies are not “slightly invasive” when working with adults or children with an intellectual disability like Down Syndrome. The oversight committees that evaluate the ethics of a proposed human research study often denied such procedures. And even when they are approved, patients or caregivers have often dropped out of studies due to the biopsy method. This sensitive situation has hampered the progress of iPSC-based studies of Down Syndrome.

This week, a research team at Case Western Reserve University School of Medicine reported in STEM CELLS Translational Medicine that they’ve overcome this obstacle with a truly non-invasive procedure: collect cells via urine samples. But wait there’s more. It turns out that iPSCs derived from urine are more stable than their skin biopsy counterparts. The team believes it’s because skin cells, unlike cells found in urine, are exposed to the sunlight’s DNA-damaging UV radiation.

So far the team has banked iPSC lines from ten individuals with Down Syndrome which they will share with other researchers. Team lead Alberto Costa described the importance of these cell lines in a press release:

“Our methods represent a significant improvement in iPSC technology, and should be an important step toward the development of human cell-based platforms that can be used to test new medications designed to improve the quality of life of people with Down syndrome.”

ICYMI the CIRM Alpha Stem Cell Clinic Symposium Talks are Now on YouTube!
Last week, City of Hope hosted a fantastic meeting featuring the efforts of our CIRM Alpha Stem Cell Clinics. It was the second annual symposium and it featured talks from scientists, doctors, patients and advocates about the advancements in stem cell-based clinical trials and the impacts those trials have had on the lives of patients.

We wrote about the symposium earlier this week, but we couldn’t capture all the amazing talks and stories that were shared throughout the day. Luckily, the City of Hope filmed all the talks and they are now available on YouTube. Below are a few that we selected, but be sure to check out the rest on the City of Hope YouTube page.


CIRM President and CEO Randy Mills highlights the goals of the CIRM Alpha Clinics Network and what’s been achieved since its inception in 2014. 


CIRM’s Geoffrey Lomax talks about how the vision of the Alpha Clinics has turned into a reality for patients.

CIRM-funded UC Irvine Scientist, Henry Klassen, talks about his promising stem cell clinical trial for patients with a blinding disease called Retinitis Pigmentosa.

Stem cell stories that caught our eye: spinal cord injury trial update, blood stem cells in lungs, and using parsley for stem cell therapies

More good news on a CIRM-funded trial for spinal cord injury. The results are now in for Asterias Biotherapeutics’ Phase 1/2a clinical trial testing a stem cell-based therapy for patients with spinal cord injury. They reported earlier this week that six out of six patients treated with 10 million AST-OPC1 cells, which are a type of brain cell called oligodendrocyte progenitor cells, showed improvements in their motor function. Previously, they had announced that five of the six patients had shown improvement with the jury still out on the sixth because that patient was treated later in the trial.

 In a news release, Dr. Edward Wirth, the Chief Medical officer at Asterias, highlighted these new and exciting results:

 “We are excited to see the sixth and final patient in the AIS-A 10 million cell cohort show upper extremity motor function improvement at 3 months and further improvement at 6 months, especially because this particular patient’s hand and arm function had actually been deteriorating prior to receiving treatment with AST-OPC1. We are very encouraged by the meaningful improvements in the use of arms and hands seen in the SciStar study to date since such gains can increase a patient’s ability to function independently following complete cervical spinal cord injuries.”

Overall, the trial suggests that AST-OPC1 treatment has the potential to improve motor function in patients with severe spinal cord injury. So far, the therapy has proven to be safe and likely effective in improving some motor function in patients although control studies will be needed to confirm that the cells are responsible for this improvement. Asterias plans to test a higher dose of 20 million cells in AIS-A patients later this year and test the 10 million cell dose in AIS-B patients that a less severe form of spinal cord injury.

 Steve Cartt, CEO of Asterias commented on their future plans:

 “These results are quite encouraging, and suggest that there are meaningful improvements in the recovery of functional ability in patients treated with the 10 million cell dose of AST-OPC1 versus spontaneous recovery rates observed in a closely matched untreated patient population. We look forward to reporting additional efficacy and safety data for this cohort, as well as for the currently-enrolling AIS-A 20 million cell and AIS-B 10 million cell cohorts, later this year.”

Lungs aren’t just for respiration. Biology textbooks may be in need of some serious rewrites based on a UCSF study published this week in Nature. The research suggests that the lungs are a major source of blood stem cells and platelet production. The long prevailing view has been that the bone marrow was primarily responsible for those functions.

The new discovery was made possible by using special microscopy that allowed the scientists to view the activity of individual cells within the blood vessels of a living mouse lung (watch the fascinating UCSF video below). The mice used in the experiments were genetically engineered so that their platelet-producing cells glowed green under the microscope. Platelets – cell fragments that clump up and stop bleeding – were known to be produced to some extent by the lungs but the UCSF team was shocked by their observations: the lungs accounted for half of all platelet production in these mice.

Follow up experiments examined the movement of blood cells between the lung and bone marrow. In one experiment, the researchers transplanted healthy lungs from the green-glowing mice into a mouse strain that lacked adequate blood stem cell production in the bone marrow. After the transplant, microscopy showed that the green fluorescent cells from the donor lung traveled to the host’s bone marrow and gave rise to platelets and several other cells of the immune system. Senior author Mark Looney talked about the novelty of these results in a university press release:

Mark Looney, MD

“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia [low platelet count].”

If this newfound role of the lung is shown to exist in humans, it may provide new therapeutic approaches to restoring platelet and blood stem cell production seen in various diseases. And it will give lung transplants surgeons pause to consider what effects immune cells inside the donor lung might have on organ rejection.

Add a little vanilla to this stem cell therapy. Typically, the only connection between plants and stem cell clinical trials are the flowers that are given to the patient by friends and family. But research published this week in the Advanced Healthcare Materials journal aims to use plant husks as part of the cell therapy itself.

Though we tend to focus on the poking and prodding of stem cells when discussing the development of new therapies, an equally important consideration is the use of three-dimensional scaffolds. Stem cells tend to grow better and stay healthier when grown on these structures compared to the flat two-dimensional surface of a petri dish. Various methods of building scaffolds are under development such as 3D printing and designing molds using materials that aren’t harmful to human tissue.

Human fibroblast cells growing on decellularized parsley.
Image: Gianluca Fontana/UW-Madison

But in the current study, scientists at the University of Wisconsin-Madison took a creative approach to building scaffolds: they used the husks of parsley, vanilla and orchid plants. The researchers figured that millions of years of evolution almost always leads to form and function that is much more stable and efficient than anything humans can create. Lead author Gianluca Fontana explained in a university press release how the characteristics of plants lend themselves well to this type of bioengineering:

Gianluca Fontana, PhD

“Nature provides us with a tremendous reservoir of structures in plants. You can pick the structure you want.”

The technique relies on removing all the cells of the plant, leaving behind its outer layer which is mostly made of cellulose, long chains of sugars that make up plant cell walls. The resulting hollow, tubular husks have similar shapes to those found in human intestines, lungs and the bladder.

The researchers showed that human stem cells not only attach and grow onto the plant scaffolds but also organize themselves in alignment with the structures’ patterns. The function of human tissues rely on an organized arrangement of cells so it’s possible these plant scaffolds could be part of a tissue replacement cell product. Senior author William Murphy also points out that the scaffolds are easily altered:

William Murphy, PhD

“They are quite pliable. They can be easily cut, fashioned, rolled or stacked to form a range of different sizes and shapes.”

And the fact these scaffolds are natural products that are cheap to manufacture makes this a project well worth watching.

Stem Cell Stories that Caught our Eye: stem cell insights into anorexia, Zika infection and bubble baby disease

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cell model identifies new culprit for anorexia.

Eating disorders like anorexia nervosa are often thought to be caused by psychological disturbances or societal pressure. However, research into the genes of anorexia patients suggests that what’s written in your DNA can be associated with an increased vulnerability to having this disorder. But identifying individual genes at fault for a disease this complex has remained mostly out of scientists’ reach, until now.

A CIRM-funded team from the UC San Diego (UCSD) School of Medicine reported this week that they’ve developed a stem cell-based model of anorexia and used it to identify a gene called TACR1, which they believe is associated with an increased likelihood of getting anorexia.

They took skin samples from female patients with anorexia and reprogrammed them into induced pluripotent stem cells (iPSCs). These stem cells contained the genetic information potentially responsible for causing their anorexia. The team matured these iPSCs into brain cells, called neurons, in a dish, and then studied what genes got activated. When they looked at the genes activated by anorexia neurons, they found that TACR1, a gene associated with psychiatric disorders, was switched on higher in anorexia neurons than in healthy neurons. These findings suggest that the TACR1 gene could be an identifier for this disease and a potential target for developing new treatments.

In a UCSD press release, Professor and author on the study, Alysson Muotri, said that they will follow up on their findings by studying stem cell lines derived from a larger group of patients.

Alysson Muotri UC San Diego

“But more to the point, this work helps make that possible. It’s a novel technological advance in the field of eating disorders, which impacts millions of people. These findings transform our ability to study how genetic variations alter brain molecular pathways and cellular networks to change risk of anorexia nervosa — and perhaps our ability to create new therapies.”

Anorexia is a disease that affects 1% of the global population and although therapy can be an effective treatment for some, many do not make a full recovery. Stem cell-based models could prove to be a new method for unlocking new clues into what causes anorexia and what can cure it.

Nature versus Zika, who will win?

Zika virus is no longer dominating the news headlines these days compared to 2015 when large outbreaks of the virus in the Southern hemisphere came to a head. However, the threat of Zika-induced birth defects, like microcephaly to pregnant women and their unborn children is no less real or serious two years later. There are still no effective vaccines or antiviral drugs that prevent Zika infection but scientists are working fast to meet this unmet need.

Speaking of which, scientists at UCLA think they might have a new weapon in the war against Zika. Back in 2013, they reported that a natural compound in the body called 25HC was effective at attacking viruses and prevented human cells from being infected by viruses like HIV, Ebola and Hepatitis C.

When the Zika outbreak hit, they thought that this compound could potentially be effective at preventing Zika infection as well. In their new study published in the journal Immunity, they tested a synthetic version of 25HC in animal and primate models, they found that it protected against infection. They also tested the compound on human brain organoids, or mini brains in a dish made from pluripotent stem cells. Brain organoids are typically susceptible to Zika infection, which causes substantial cell damage, but this was prevented by treatment with 25HC.

Left to right: (1) Zika virus (green) infects and destroys the formation of neurons (pink) in human stem cell-derived brain organoids.  (2) 25HC blocks Zika infection and preserves neuron formation in the organoids. (3) Reduced brain size and structure in a Zika-infected mouse brain. (4) 25HC preserves mouse brain size and structure. Image courtesy of UCLA Stem Cell.

A UCLA news release summarized the impact that this research could have on the prevention of Zika infection,

“The new research highlights the potential use of 25HC to combat Zika virus infection and prevent its devastating outcomes, such as microcephaly. The research team will further study whether 25HC can be modified to be even more effective against Zika and other mosquito-borne viruses.”

Harnessing a naturally made weapon already found in the human body to fight Zika could be an alternative strategy to preventing Zika infection.

Gene therapy in stem cells gives hope to bubble-babies.

Last week, an inspiring and touching story was reported by Erin Allday in the San Francisco Chronicle. She featured Ja’Ceon Golden, a young baby not even 6 months old, who was born into a life of isolation because he lacked a properly functioning immune system. Ja’Ceon had a rare disease called severe combined immunodeficiency (SCID), also known as bubble-baby disease.

 

Ja’Ceon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski. Photo: Santiago Mejia, The Chronicle.

Babies with SCID lack the body’s immune defenses against infectious diseases and are forced to live in a sterile environment. Without early treatment, SCID babies often die within one year due to recurring infections. Bone marrow transplantation is the most common treatment for SCID, but it’s only effective if the patient has a donor that is a perfect genetic match, which is only possible for about one out of five babies with this disease.

Advances in gene therapy are giving SCID babies like Ja’Ceon hope for safer, more effective cures. The SF Chronicle piece highlights two CIRM-funded clinical trials for SCID run by UCLA in collaboration with UCSF and St. Jude Children’s Research Hospital. In these trials, scientists isolate the bone marrow stem cells from SCID babies, correct the genetic mutation causing SCID in their stem cells, and then transplant them back into the patient to give them a healthy new immune system.

The initial results from these clinical trials are promising and support other findings that gene therapy could be an effective treatment for certain genetic diseases. CIRM’s Senior Science Officer, Sohel Talib, was quoted in the Chronicle piece saying,

“Gene therapy has been shown to work, the efficacy has been shown. And it’s safe. The confidence has come. Now we have to follow it up.”

Ja’Ceon was the first baby treated at the UCSF Benioff Children’s Hospital and so far, he is responding well to the treatment. His great aunt Dannie Hawkins said that it was initially hard for her to enroll Ja’Ceon in this trial because she was a partial genetic match and had the option of donating her own bone-marrow to help save his life. In the end, she decided that his involvement in the trial would “open the door for other kids” to receive this treatment if it worked.

Ja’Ceon Golden plays with patient care assistant Grace Deng in a sterile play area at UCSF Benioff Children’s Hospital.Photo: Santiago Mejia, The Chronicle

It’s brave patients and family members like Ja’Ceon and Dannie that make it possible for research to advance from clinical trials into effective treatments for future patients. We at CIRM are eternally grateful for their strength and the sacrifices they make to participate in these trials.