Streamlining Stem Cell Therapy Development for Impatient Patients

During this third week of the Month of CIRM, we are focusing on CIRM’s Infrastructure programs which are all focused on helping to accelerate stem cell treatments to patients with unmet medical needs.

Time is money. It’s a cliché but still very true, especially in running a business. The longer it takes to get things done, the more costs you’ll most likely face. But in the business of developing new medical therapies, time is also people’s lives.

Currently, it takes about eight years to move a promising stem cell treatment from the lab into clinical trials. For patients with fatal, incurable diseases, that is eight years too long. And even when promising therapies reach clinical trials, only about 1 out of 10 get approved, according to a comprehensive 2014 study in Nature Biotechnology. These sobering stats slow the process of getting treatments to patients with unmet medical needs.

While a lack of therapy effectiveness or safety play into the low success rate, other factors can have a significant impact on the delay or suspension of a trial. An article, “Why Do Clinical Trials Fail?” in Clinical Trials Arena from a couple years back outlined a few. Here’s a snippet from that article:

  • “Poor study design: Selecting the wrong patients, the wrong dosing and the wrong endpoint, as well as bad data and bad site management cause severe problems.”
  • “Complex protocol: Simple is better. A complex protocol, which refers to trying to answer too many questions in one single trial, can produce faulty data and contradictory results.”
  • “Poor management: A project manager who does not have enough experience in costing and conducting clinical trials will lead to weak planning, with no clear and real timelines, and to ultimate failure.”

CIRM recognized that these clinical trial planning and execution setbacks can stem from the fact that, although lab researchers are experts at transforming an idea into a candidate therapy, they may not be masters in navigating the complex regulatory requirements of the Food and Drug Administration (FDA). Many simply don’t have the experience to get those therapies off the ground by themselves.

Lab researchers are experts at transforming an idea into a candidate therapy but most are inexperienced at navigating the complex regulatory requirements of the Food and Drug Administration (FDA).

So, to help make this piece of the therapy development process more efficient and faster, the CIRM governing Board last year approved the launch of the Translating Center and Accelerating Center: two novel infrastructure programs which CIRM grantees can tap into as they carry their promising candidate therapies from lab experiments in cells to preclinical studies in animals to clinical trials in people. Both centers were awarded to QuintilesIMS which collectively dubbed them The Stem Cell Center.

The Stem Cell Center acts as a one-stop-shop, stem cell therapy development support system for current and prospective CIRM grantees, giving them advanced priority for QuintilesIMS services. So how does it work? When a scientist’s initial idea for a cell therapy gains traction and, through a lot of effort in the lab, matures into a bona fide therapy candidate to treat a particular disease, the next big step is to prepare the therapy for testing in people. But that’s easier said than done. To ensure safety, the Food and Drug Administration requires a rigorous set of tests and documentation that make up an Investigational New Drug (IND) application, which must be submitted before any testing in people take can place in the U.S.

That’s where the Translation Center comes into the picture. It carries out the necessary research activities to show, as much as is possible in animals, that the therapy is safe. The Translating Center also helps at this stage with manufacturing the cell therapy product so that it’s of a consistent quality for both the preclinical and future clinical trial studies. If all goes as planned, the grantee will have the necessary pieces to file an IND. At this stage, the Translating Center coordinates with the Accelerating Center which focuses on supporting the many facets of a clinical study including the IND filing, clinical trial design, monitoring of patient safety, and project management.

Because the work of Translating and Accelerating Centers is focused on these regulatory activities day in and day out, they have the know-how to pave a clearer path, with fewer pitfalls, for the grantee to navigate the complex maze we call cell therapy development. It’s not just helpful for the researchers seeking approval from the FDA, but it helps the FDA too. Because cell therapies are still so new, creating a standardized, uniform approach to stem cell-based clinical trial projects will help the FDA streamline their evaluation of the projects.

Ultimately, and most importantly, all of those gears running smoothly in sync will help leave a lasting legacy for California and the world: an acceleration in the development of stem cell treatment for patients with unmet medical needs.


Caught our eye: new Americans 4 Cures video, better mini-brains reveal Zika insights and iPSC recipes go head-to-head

How stem cell research gives patients hope (Karen Ring).
You can learn about the latest stem cell research for a given disease in seconds with a quick google search. You’ll find countless publications, news releases and blogs detailing the latest advancements that are bringing scientists and clinicians closer to understanding why diseases happen and how to treat or cure them.

But one thing these forms of communications lack is the personal aspect. A typical science article explains the research behind the study at the beginning and ends with a concluding statement usually saying how the research could one day lead to a treatment for X disease. It’s interesting, but not always the most inspirational way to learn about science when the formula doesn’t change.

However, I’ve started to notice that more and more, institutes and organizations are creating videos that feature the scientists/doctors that are developing these treatments AND the patients that the treatments could one day help. This is an excellent way to communicate with the public! When you watch and listen to a patient talk about their struggles with their disease and how there aren’t effective treatments at the moment, it becomes clear why funding and advancing research is important.

We have a great example of a patient-focused stem cell video to share with you today thanks to our friends at Americans for Cures, a non-profit organization that advocates for stem cell research. They posted a new video this week in honor of Stem Cell Awareness Day featuring patients and patient advocates responding to the question, “What does stem cell research give you hope for?”. Many of these patients and advocates are CIRM Stem Cell Champions that we’ve featured on our website, blog, and YouTube channel.

Americans for Cures is encouraging viewers to take their own stab at answering this important question by sharing a short message (on their website) or recording a video that they will share with the stem cell community. We hope that you are up for the challenge!

Mini-brains help uncover some of Zika’s secrets (Kevin McCormack).
One of the hardest things about trying to understand how a virus like Zika can damage the brain is that it’s hard to see what’s going on inside a living brain. That’s not surprising. It’s not considered polite to do an autopsy of someone’s brain while they are still using it.

Human organoid_800x533

Microscopic image of a mini brain organoid, showing layered neural tissue and different groups of neural stem cells (in blue, red and magenta) giving rise to neurons (green). Image: Novitch laboratory/UCLA

But now researchers at UCLA have come up with a way to mimic human brains, and that is enabling them to better understand how Zika inflicts damage on a developing fetus.

For years researchers have been using stem cells to help create “mini brain organoids”, essentially clusters of some of the cells found in the brain. They were helpful in studying some aspects of brain behavior but limited because they were very small and didn’t reflect the layered complexity of the brain.

In a study, published in the journal Cell Reports, UCLA researchers showed how they developed a new method of creating mini-brain organoids that better reflected a real brain. For example, the organoids had many of the cells found in the human cortex, the part of the brain that controls thought, speech and decision making. They also found that the different cells could communicate with each other, the way they do in a real brain.

They used these organoids to see how the Zika virus attacks the brain, damaging cells during the earliest stages of brain development.

In a news release, Momoko Watanabe, the study’s first author, says these new organoids can open up a whole new way of looking at the brain:

“While our organoids are in no way close to being fully functional human brains, they mimic the human brain structure much more consistently than other models. Other scientists can use our methods to improve brain research because the data will be more accurate and consistent from experiment to experiment and more comparable to the real human brain.”

iPSC recipes go head-to-head: which one is best?
In the ten years since the induced pluripotent stem cell (iPSC) technique was first reported, many different protocols, or recipes, for reprogramming adult cells, like skin, into iPSCs have been developed. These variations bring up the question of which reprogramming recipe is best. This question isn’t the easiest to answer given the many variables that one needs to test. Due to the cost and complexity of the methods, comparisons of iPSCs generated in different labs are often performed. But one analysis found significant lab-to-lab variability which can really muck up the ability to make a fair comparison.

A Stanford University research team, led by Dr. Joseph Wu, sought to eliminate these confounding variables so that any differences found could be attributed specifically to the recipe. So, they tested six different reprogramming methods in the same lab, using cells from the same female donor. And in turn, these cells were compared to a female source of embryonic stem cells, the gold standard of pluripotent stem cells. They reported their findings this week in Nature Biomedical Engineering.

Previous studies had hinted that the reprogramming protocol could affect the ability to fully specialize iPSCs into a particular cell type. But based on their comparisons, the protocol chosen did not have a significant impact on how well iPSCs can be matured. Differences in gene activity are a key way that researchers do side-by-side comparisons of iPSCs and embryonic stem cells. And based on the results in this study, the reprogramming method itself can influence the differences. A gene activity comparison of all the iPSCs with the embryonic stem cells found the polycomb repressive complex – a set of genes that play an important role in embryonic development and are implicated in cancer – had the biggest difference.

In a “Behind the Paper” report to the journal, first author Jared Churko, says that based on these findings, their lab now mostly uses one reprogramming protocol – which uses the Sendai virus to deliver the reprogramming genes to the cells:

“The majority of our hiPSC lines are now generated using Sendai virus. This is due to the ease in generating hiPSCs using this method as well as the little to no chance of transgene integration [a case in which a reprogramming gene inserts into the cells’ DNA which could lead to cancerous growth].”

Still, he adds a caveat that the virus does tend to linger in the cells which suggests that:

“cell source or reprogramming method utilized, each hiPSC line still requires robust characterization prior to them being used for downstream experimentation or clinical use.”


Saving Ronnie: Stem Cell & Gene Therapy for Fatal Bubble Baby Disease [Video]

During this second week of the Month of CIRM, we’ve been focusing on the people who are critical to accomplishing our mission to accelerate stem cell treatments to patients with unmet medical needs.

These folks include researchers, like Clive Svendsen and his team at Cedars-Sinai Medical Center who are working tirelessly to develop a stem cell therapy for ALS. My colleague Karen Ring, CIRM’s Social Media and Website Manager, featured Dr. Svendsen and his CIRM-funded clinical trial in Monday’s blog. And yesterday, in recognition of Stem Cell Awareness Day, Kevin McCormack, our Senior Director of Public Communications, blogged about the people within the stem cell community who have made, and continue to make, the day so special.

Today, in a new video, I highlight a brave young patient, Ronnie, and his parents who decided to participate in a CIRM-funded clinical trial run by St. Jude Children’s Research Hospital and UC San Francisco in an attempt to save Ronnie’s life from an often-fatal disease called severe combined immunodeficiency (SCID). This disorder, also known as bubble baby disease, leaves newborns without a functioning immune system which can turn a simple cold into a potentially deadly infection.

Watch this story’s happy ending in the video above.

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

CIRM-Funded Clinical Trials Targeting Blood and Immune Disorders

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

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our blood and immune disorders portfolio, specifically focusing on sickle cell disease, HIV/AIDS, severe combined immunodeficiency (SCID, also known as bubble baby disease) and rare disease called chronic granulomatous disease (CGD).

CIRM has funded a total of eight trials targeting these disease areas, all of which are currently active. Check out the infographic below for a list of those trials.

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

CIRM-Funded Clinical Trials Targeting Cancers

Welcome to the Month of CIRM!

As we mentioned in last Thursday’s blog, during the month of October we’ll be looking back at what CIRM has done since the agency was created by the people of California back in 2004. To start things off, we’ll be focusing on CIRM-funded clinical trials this week. Supporting clinical trials through our funding and partnership is a critical cornerstone to achieving our mission: to accelerate stem cell treatments to patients with unmet medical needs.

Over the next four days, we will post infographics that summarize CIRM-funded trials focused on therapies for cancer, neurologic disorders, heart and metabolic disease, and blood disorders. Today, we review the nine CIRM-funded clinical trial projects that target cancer. The therapeutic strategies are as varied as the types of cancers the researchers are trying to eradicate. But the common element is developing cutting edge methods to outsmart the cancer cell’s ability to evade standard treatment.

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

An unexpected link: immune cells send muscle injury signal to activate stem cell regeneration

We’ve written many blogs over the years about research focused on muscle stem cell function . Those stories describe how satellite cells, another name for muscle stem cells, lay dormant but jump into action to grow new muscle cells in response to injury and damage. And when satellite function breaks down with aging as well as with diseases like muscular dystrophy, the satellite cells drop in number and/or lose their capacity to divide, leading to muscle degeneration.

Illustration of satellite cells within muscle fibers. Image source: APSU Biology

One thing those research studies don’t focus on is the cellular and molecular signals that cause the satellite cells to say, “Hey! We need to start dividing and regenerating!” A Stanford research team examining this aspect of satellite cell function reports this week in Nature Communications that immune cells play an unexpected role in satellite cell activation. This study, funded in part by CIRM, provides a fundamental understanding of muscle regeneration and repair that could aid the development of novel treatments for muscle disorders.

ADAMTS1: a muscle injury signal?
To reach this conclusion, the research team drew upon previous studies that indicated a gene called Adamts1 was turned on more strongly in the activated satellite cells compared to the dormant satellite cells. The ADAMTS1 protein is a secreted protein so the researchers figured it’s possible it could act as a muscle injury signal that activates satellites cells. When ADAMTS1 was applied to mouse muscle fibers in a petri dish, satellite cells were indeed activated.

Next, the team examined ADAMTS1 in a mouse model of muscle injury and found the protein clearly increased within one day after muscle injury. This timing corresponds to when satellite cells drop out of there dormant state after muscle injury and begin dividing and specializing into new muscle cells. But follow up tests showed the satellite cells were not the source of ADAMTS1. Instead, a white blood cell called a macrophage appeared to be responsible for producing the protein at the site of injury. Macrophages, which literally means “big eaters”, patrol our organs and will travel to sites of injury and infection to keep them clean and healthy by gobbling up dead cells, bacteria and viruses. They also secrete various proteins to alert the rest of the immune system to join the fight against infection.

Immune cell’s double duty after muscle injury: cleaning up the mess and signaling muscle regeneration
To confirm the macrophages’ additional role as the transmitter of this ADAMTS1 muscle injury signal, the researchers generated transgenic mice whose macrophages produce abnormally high levels of ADAMTS1. The activation of satellite cells in these mice was much higher than in normal mice lacking this boost of ADAMTS1 production. And four months after birth, the increased activation led to larger muscles in the transgenic mice. In terms of muscle regeneration, one-month old transgenic mice recovered from muscle injury faster than normal mice. Stanford professor Brian Feldman, MD, PhD, the senior author of the study, described his team’s initial reaction to their findings in an interview with Scope, Stanford Medicine’s blog:

“While, in retrospect, it might make intuitive sense that the same cells that are sent into a site of injury to clean up the mess also carry the tools and signals needed to rebuild what was destroyed, it was not at all obvious how, or if, these two processes were biologically coupled. Our data show a direct link in which the clean-up crew releases a signal to launch the rebuild. This was a surprise.”

Further experiments showed that ADAMTS1 works by chopping up a protein called NOTCH that lies on the surface of satellite cells. NOTCH provides signals to the satellite cell to stay in a dormant state. So, when ADAMTS1 degrades NOTCH, the dormancy state of the satellite cells is lifted and they begin to divide and transform into muscle cells.

A pathway to novel muscle disorder therapies?
One gotcha with the ADAMTS1 injury signal is that too much activation can lead to a depletion of satellite cells. In fact, after 8 months, muscle regeneration actually weakened in the transgenic mice that were designed to persistently produce the protein. Still, this novel role of macrophages in stimulating muscle regeneration via the secreted ADAMTS1 protein opens a door for the Stanford team to explore new therapeutic approaches to treating muscle disorders:

“We are excited to learn that a single purified protein, that functions outside the cell, is sufficient to signal to muscle stem cells and stimulate them to differentiate into muscle,” says Dr. Feldman. “The simplicity of that type of signal in general and the extracellular nature of the mechanism in particular, make the pathway highly tractable to manipulation to support efforts to develop therapies that improve health.”

Bioengineers make breathtaking step toward building a lung

Tissue engineers have made amazing progress when it comes to using stem cells to build tissues such as blood vessels, which have relatively simple tubular shape. In fact, a late stage CIRM-funded clinical trial run by Humacyte is testing an engineered vein to improve dialysis treatment for people with kidney disease. Building a lung that works properly, on the other hand, has proven elusive due in no small part to its extremely intricate structure. But in a Science Advances report published yesterday, Columbia University bioengineers describe a potentially breakthrough method for building a functional lung in the lab.

Building a better lung that removes and repopulates lung cells without hurting blood vessels. Figure courtesy of N. Valerio Dorrello and Gordana Vunjak-Novakovic, Columbia University.

Lung disease tends to not get as much attention as other deadly diseases like cancer and heart failure. Yet it’s the world’s third leading cause of death with 400,000 deaths per year in just the United States. The only true treatment is a very drastic one: a lung transplant. This option is not very attractive even to those with severe disease because it’s a very expensive procedure that only has a 10-20% survival rate after 10 years. On top of that, donor lungs are in very short supply. So, clinicians and their patients are in desperate need for other approaches.

Tissue engineering approaches to building a lung face many challenges due to the organ’s complex structure. How complex, you ask? Science writer and scientist, Shelly Fan, uses a great analogy to describe it in her Singularity Hub article about this study:

“The lung is a real jungle: at the microscopic level, the tree-like airways contain alveoli, tiny bubble-like structures where the lungs exchange gas with our blood. Both arteries and veins enwrap the alveoli like two sets of mesh pockets.”

Now, one approach to building an organ is to start from scratch by manufacturing a synthetic scaffold resembling the shape of the organ and then seeding it with stem cells or other precursor cells. But because of this complicated microscopic jungle, bioengineers have steered clear of this path. Instead, the Columbia team has generated a natural scaffold by removing the cells from rat lungs using detergents. What’s left behind is a lung “skeleton” of proteins and molecules called the extracellular matrix that’s devoid of cells.

Building a better lung that removes and repopulates lung cells without hurting blood vessels. Figure courtesy of N. Valerio Dorrello and Gordana Vunjak-Novakovic, Columbia University.

In previous experiments using rat lungs, the team stripped out the lung cells, called epithelial cells, which are the type typically damaged in lung disease. Their method also removed the blood vessel cells, called endothelial cells, which make up the vascular system that is key to taking up the oxygen inhaled into the lungs. While repopulating the functional epithelial cells has been achieved, restoring the blood vessels is another story as mentioned in a university press release:

“An intact vascular network—missing in these scaffolds—is critical not only for maintaining the blood-gas barrier and allowing for proper graft function, but also for supporting the cells introduced to regenerate the lung. This has proved to be a daunting challenge.”

So, the current study attempted to only clear out the lung epithelial cells without disturbing the blood vessels to see if they would have better results. This approach makes sense on another level when envisioning future clinical applications: the therapy would be less complex if you only had to remove the diseased cells, which typically are the lung epithelial cells.

The researchers devised a cell removal method that was specific to the airways so that only epithelial cells would be cleared away. A battery of tests showed that, that although the lungs lost much of their ability to inflate and expand, the blood system remained intact after the procedure. The team then introduced either human epithelial cells or human induced pluripotent stem cell-derived epithelial cells into the scaffold. Within a day, they watched as the cells began to repopulate the lung in the correct areas. Follow-up experiments showed that the addition of new epithelial cells restored a good portion of the lungs expansion abilities.

Lead author, Dr. N. Valerio Dorrello, gave a big picture perspective on how this proof-of-concept study could one day help those who suffer from lung disease:

Nicolino Valerio Dorrello, MD

“Every day, I see children in intensive care with severe lung disease who depend on mechanical ventilation support. The approach we established could lead to entirely new treatment modalities for these patients, designed to regenerate lungs by treating their injured epithelium.”

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

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

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

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

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

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

Attractive new regenerative medicine tool uses magnets to shape and stimulate stem cells

The ultimate goal of tissue engineers who work in the regenerative medicine field is to replace damaged or diseased organs with new ones built from stem cells. To accomplish the feat, these researchers are developing new tools and techniques to manipulate and specialize stem cells into three dimensional structures. Some popular methods – which we’ve blogged about often – include the use of bioscaffolds as well as 3D bioprinting . This week, a research team at the Laboratoire Matière et Systèmes Complexes in France has developed an attractive (pun intended!) new tool that uses magnetized stem cells to both manipulate and stimulate the cells into 3D shapes.

The magnetic stretcher: this all-in-one system can both form and mechanically stimulate an aggregate of magnetized embryonic stem cells. Image: © Claire Wilhelm / Laboratoire Matière et systèmes complexes (CNRS/Université Paris Diderot).

The study, reported on Monday in Nature Communications, used embryonic stem cells which were incubated with magnetic nanoparticles. The cells readily take up the nanoparticles which allowed the scientists to group the individual cells using magnets. But first the team needed to show that the nanoparticles had no negative effects on the cells. Comparing the iron nanoparticle-laden stem cells to iron-free cells showed no difference in the cells’ survival and their ability to divide.

It was also important to make sure the introduction of nanoparticles had no impact on the stem cell’s pluripotency; that is, its ability to maintain its unspecialized state. A visual check of the cells through a microscope showed that they grew together in rounded clumps, a hallmark of undifferentiated, pluripotent cells. In addition, the key genes that bestow pluripotency onto embryonic stem cells were still active after the addition of the nanoparticles.

The stem cells’ ability to mature into various cell types, like heart muscle or nerve, is key to any successful tissue engineering project. So, the next important assessment of these magnetized cells was to make sure their ability to differentiate, or specialize, was still intact. The typical first step to differentiating embryonic stem cells is to form so-called embryoid bodies (EBs), which are 3D groups of pluripotent stem cells which begin differentiating into the three fundamental tissues types: mesoderm (gives rise to muscle, bone, fat), ectoderm (gives rise to nerve, hair, eyes), endoderm (gives rise to intestines, liver). Using a popular technique, called the hanging drop method, the team showed that the presence of the nanoparticles did not negatively affect embryoid body formation.

In fact, the use of magnets to form embryoid bodies provided several advantages over the hanging drop method. The hanging drop technique requires multiple, time-consuming steps and the resulting embryoid bodies tend to be inconsistent in size and shape. Use of the magnets, on the other hand, instantaneously assembled the stem cells into consistently round aggregates. And by precisely adjusting the magnetic force used, the scientists could also vary the size of the embyroid body, which is an important variable to control since the embryoid size can impact its ability to differentiate.

While the magnet used to form the embryoid bodies was kept stable, the researchers included another magnet which they could move. With this setup, the team was able to stretch and shape the group of cells without the need of scaffolds or the need to physically contact the cells. Several previous studies, using flat, 2-dimensional petri dishes, have shown that the stiffness and flexibility of the dish can stimulate gene activity by affecting cell shape. In this study, the researchers found that when the magnet was moved in a cyclical pattern that imitates the rhythm of a heart beat, the embryoid bodies were, if you can believe it, nudged toward a heart muscle fate. A press release by France’s National Center of Scientific Research (CNRS), which funded the study, explained the big picture implications of this new technique:

“This “all-in-one” approach, which makes it possible to build and manipulate tissue within the same system, could thus prove to be a powerful tool both for biophysical studies and tissue engineering.”

UCLA launches CIRM-funded clinical trial using engineered blood stem cells to fight hard-to-treat cancers

It’s not uncommon for biomedical institutes as well as their funding partners to announce through press releases that a clinical trial they’re running has gotten off the ground and has started to enroll patients. For an outsider looking in, it may seem like they’re jumping the gun a bit. No patients have received the therapy. No cures have been declared. So why all the hubbub at the start?

The reality is this: the launch of a clinical trial isn’t a beginning. It represents many years of effort by many researchers and a lot of funding to take an idea and develop it into a tangible product that has been given clearance to be tested in people to potentially save their lives. That’s why this important milestone deserves to be recognized. So, we were excited to get the word out, in the form of a press release , that UCLA had announced this morning the launch of a CIRM-funded clinical trial testing a therapy for hard-to-treat cancers.

The UCLA clinical trial procedure will genetically alter a patient’s hematopoietic stem cells and T cells to give rise to a steady supply of T cells that are efficient cancer killers.

It’s estimated that metastasis, or the spread of cancer to other parts of the body, is responsible for 90% of cancer deaths. Though radiation and chemotherapy treatments can stop a tumor in its tracks, a small population of cancer stem cells in the tumor lie dormant and can evade those anti-cancer approaches. Because of their unlimited potential to divide, the cancer stem cells regrow the tumor leading to its inevitable return and spread. Oncologists clearly need new approaches to help patients with this unmet medical need.

That’s where today’s clinical trial launch comes into the picture. Dr. Antonio Ribas, a member of the UCLA Broad Stem Cell Research Center, and his team will genetically engineer cancer-killing white blood cells called T cells and blood-forming stem cells collected from patients to produce a protein receptor that recognizes a protein found almost exclusively on the surface of many types of cancer. When the T cells are transfused back into the patient, they can more efficiently track down and eradicate hard-to-treat cancer stem cells. At the same time, the transfused blood stem cells – which specialize into all the various immune system cells – will provide a long-term supply of T cells for continued protection against reoccurrence of the tumor.

“Few options exist for the treatment of patients whose cancers have metastasized due to resistance to current therapies,” Ribas said in the UCLA press release. “This clinical trial will allow us to try a new approach that engineers the body’s immune system to fight metastasized tumors similar to how it fights germs and viruses.”


And as Dr. Maria Millan, CIRM’s President & CEO (interim), described in our accompanying press release, CIRM will be an ever-present partner to help Ribas’ team get the clinical trial smoothly out of the starting gate and provide the support needed to carry the therapy to its completion:

“This trial is the first step in developing a therapy that could alleviate the complications resulting from cancer metastases as well as potentially improving outcomes in cancer patients where there are currently no effective treatment options. We are confident that CIRM’s funding and partnership, in combination with the expertise provided by our Alpha Stem Cell Clinic network, will give provide critical support for the successful conduct of this important clinical trial.”




To learn more about this clinical trial, visit its page at If you think you might be eligible to enroll, please contact Clinical Research Coordinator Justin Tran by email at or by phone at 310-206-2090.