Stem Cell Stories that Caught Our Eye: Killer Cells May Treat Cancer, CIRM-Funded Trial Shows Promise and Worms to the Rescue – New Research Could Lead to Human Therapies

Stem cell image of the week:  Our stem cell image of the week shows natural killer cells (yellow) attacking a cancer cell (red).

The cancer fighters known as CAR T cells have proved their prowess in recent years. Three therapies using the altered T cells against lymphoma or leukemia have won U.S. Food and Drug Administration approval, and hundreds of trials are now unleashing them on other malignancies, including solid tumors. But the cells may soon have company. Researchers have equipped other immune guardians—natural killer cells and macrophages—with the same type of cancer-homing receptor, and the natural killer cells have made their debut in clinical trials.


CAR T cells—their name comes from the chimeric antigen receptor, or CAR, added to help the immune cells target cancer cells—inspired the new work. CAR natural killer (CAR NK) cells could be safer, faster to produce, and cheaper, and they may work in situations where T cells falter. CAR-carrying macrophages also have potential advantages, and one firm plans to launch the first clinical trials of these cells next year.

Although they aren’t likely to replace CAR T cells, these alternative cancer fighters “could be an addition to the armamentarium of cell therapies,” says hematologist and oncologist Katy Rezvani of the University of Texas MD Anderson Cancer Center in Houston. She is leading the first trial of CAR NK cells in the United States, which began in 2017, and organizing another that is due to start this year.

“Natural killer cells are our first line of defense against cancer cells,” Rezvani says. They scan other cells in the body and destroy any that are infected or otherwise abnormal, including tumor cells. Researchers have been trying to harness the cancer-fighting activity of NK cells that don’t carry CARs for more than 20 years, notes translational immunologist Jeffrey Miller of the University of Minnesota in Minneapolis. But upgrading them by adding CARs seems to boost their potency.

CIRM-funded spinal cord injury trial produces more encouraging results (Kevin McCormack)

Way back in 2010 Geron became the first ever company to get approval from the Food and Drug Administration (FDA) to carry out a clinical trial using embryonic stem cells to treat people with spinal cord injury. CIRM funded that work and even though the company later halted the trial (for business reasons) it was a small piece of stem cell history.

Fast forward eight years and Asterias Biotherapeutics has taken up where Geron left off, using the same approach. This week Asterias published the latest results from its CIRM-funded clinical trial and they are encouraging.

They have done 24-month follow-ups on six patients (including Jake Javier and Chris Boesen who we have blogged about) who received 10 million cells transplanted into their spine. None experienced any serious side effects and MRI examinations showed evidence that the stem cells had engrafted at the injury site in all six patients. Often after a spinal cord injury a cavity can form at the injury site and scar tissue or fill up with fluid, preventing the spinal cord from healing. The evidence of engraftment means there is no such cavity.

Even more encouragingly all six have recovered at least one motor level (a measure of how much movement or function they have regained) on at least one side and five have recovered two or more motor levels on at least one side.

This kind of recovery can make the difference between needing round-the-clock care and being able to lead an independent life.

In a news release, Ed Wirth, the Chief Medical Officer at Asterias, said this shows the benefits of the therapy appear to be long-lasting:

“While the primary endpoint for the SCiStar trial was 12 months, we are further encouraged by this additional follow-up data that shows both durable engraftment and motor function recovery being maintained or improved upon at 24 months.”

The company hopes to meet with the FDA later this year to plan for a future trial of the therapy.

Planaria Worm Their Way into Human Stem Cell-Related Research (Todd Dubnicoff)

The planaria flatworm has astounding regenerative capabilities. Cut it in half and the missing side grows back. Decapitate it and the head grows back in about two weeks. Many researchers are eager to unlock the cellular and molecular mechanisms of planaria’s seemingly supernatural powers in order to bestow them onto humans suffering from disease or injury. But humans and worms are so different, how could you ever make any meaningful connections between the species?

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Decapitated planaria regrows head within a couple of weeks.                                 Photo credit: Michael Levin And Tal Shomrat, Tufts University

Well, in a report published this week, Oxford University researchers found that planaria have more in common with humans than was previously thought when it comes to the way both species regulate gene activity in stem cells. These findings make these worms an even more valid model system for exploring novel therapeutic strategies for people.

Up until this study, it was thought that only vertebrates (animals with back bones like mammals, birds and fish) use a mechanism called bivalency in their stem cells to maintain the ability to specialize into different types of cells. With bivalency, a subset of genes within stem cells are neither turned off nor turned on. Instead they’re in a “poised” state, ready to be silenced or activated depending on the eventual fate of that particular cell.

By studying the chemical modifications of DNA, called epigenetics, that play a role in gene activity and bivalency, the research team showed that bivalency is also employed by planaria, a simple invertebrate. Professor Aziz Aboobaker, the lead author on the study, explained the significance of this finding in a press release:

“The results of this approach served to confirm the team’s findings that bivalency seems likely to have evolved earlier in multicellular animal evolution than we thought, and this adds to the growing narrative that simple worm stem cells and our stem cells have much more in common then we imagined when we started this work.”

This commonality makes the easy-to-study planaria an attractive model system to study given that dysfunctions in these chemical modifications of DNA have been linked to human disease.

The study is published in Genome Research.

Regrowing dental tissue with stem cells from baby teeth


Stem cells extracted from baby teeth were able to regenerate dental pulp (shown, with fluorescent labeling) in young patients who had injured one of their adult teeth.                       Photo courtesy of University of Pennsylvania

Young children can be full of life.

For parents that bubbly energy can be fun to observe and enjoy, but in other instances when they trip and fall, or do something that causes trauma to their mouth – their teeth can take a hit. Unfortunately when that trauma affects an immature permanent tooth, it can also hinder blood supply and root development, resulting in what is essentially a “dead” tooth.

Until recently the only treatment option was apexification, a procedure which encourages root development but doesn’t always fix the lost tissue. In fact, it’s been known to cause abnormal root development.

So what is a parent to do?

Turn to a clinical trial.

New results of a clinical trial, jointly led by Songtao Shi of the University of Pennsylvania, who has also previously received funding from CIRM, and researchers at the the Fourth Military Medicine University in Xi’an, China, suggest that there is a more promising path for children with these types of injuries: using stem cells extracted from the patient’s baby teeth.

The work was published in the journal Science Translational Medicine.

“This treatment gives patients sensation back in their teeth. If you give them a warm or cold stimulation, they can feel it; they have living teeth again,” says Shi, professor and chair in the Department of Anatomy and Cell Biology in Penn’s School of Dental Medicine. “So far we have follow-up data for two, two and a half, even three years and have shown it’s a safe and effective therapy.”

The Phase I trial, conducted in China enrolled 40 children who had each injured one of their permanent incisors and still had baby teeth. Thirty were assigned to receive a treatment of human dental pulp stem cells (hDPSC) and 10 to the control treatment, apexification.

Those that received hDPSC treatment had tissue extracted from a healthy baby tooth. Upon follow-up, the researchers found that patients who received hDPSCs had more signs than the control group of healthy root development and thicker dentin, the hard part of a tooth beneath the enamel. Blood flow increased as well. A year following the procedure, only those who received hDPSCs had regained some sensation. Examining a variety of immune-system components, the team found no evidence of safety concerns.

As further support of the treatment’s effectiveness, the researchers had the opportunity to directly examine the tissue of a treated tooth when the patient re-injured it and had to have it extracted. They found that the implanted stem cells regenerated different components of dental pulp, including the cells that produce dentin, connective tissue, and blood vessels.

But this is just a first step. While using a patient’s own stem cells reduces the chances of immune rejection, it’s not possible in adult patients who have lost all of their baby teeth.

Shi and colleagues are beginning to test the use of allogenic stem cells, or cells donated from another person, to regenerate dental tissue in adults. They are also hoping to secure FDA approval to conduct clinical trials using hDPSCs in the United States.

Maria Millan Opens Up About the Current State of CIRM

In an article published to the SF Chronicle last week, reporter Erin Allday and Joaquin Palomino discussed CIRM, and how our work as an agency has paid off since our inception in 2004.

The article, which is a part of a four part series, explores the hope and reality of the revolutionary science of stem cell therapy. It focuses on what has transpired since 2004, when California voters approved a $3 billion bond measure to fund stem cell research with the promise that it soon would produce new treatments for incurable diseases.

In four parts, it follows the stories of patients desperately seeking remedies; probes the for-profit clinics where unproven and unregulated treatments are being offered; takes you into the labs and hospital rooms where scientists are testing new therapies; and provides a comprehensive accounting of what California’s multi billion dollar bet on stem cells has achieved.

Our CEO Maria Millan shared her thoughts in response to some of the questions raised by this article.

Q: There have been many critics who say it’s taking too long for CIRM to deliver cures, and they expected more. What is your response to these people?

A: Many of us can relate that relief cannot come quickly enough for our relatives and friends who suffer from debilitating and devastating medical conditions— I believe that is why many of us are at CIRM, an organization whose mission is to accelerate stem cell treatments to patients with unmet medical needs. Through the years, we have enabled the creation of an incredible ecosystem of top scientists and researchers and partnered with patients and patient advocates to pursue this mission.  We continually strive to improve and to become more efficient  and we share the sense of urgency to harness the potential of stem cell biology to deliver relief to those in need.

Q: Given all of the differences between CIRM and the NIH, why do you think the reporter compared CIRM to the NIH?

A: The NIH is the largest health research funder world-wide, has been around a lot longer, has a much larger budget >$30B this past year alone and the NHLBI alone has a $3B annual budget—NHLBI is just one of the 27 NIH Institutes. The reason that CIRM was formed is that the advocates of Proposition 71 wanted to make sure that scientists and developers can pursue vital research opportunities that may not have access to funding by traditional funders, including the NIH. CIRM has a total budget of $3B available to fund research and support operations and we have been managing that budget since the passage of Proposition 71 in 2004.  If we consider  the number of stem cell trials for given available budget, CIRM has funded a disproportionately higher number of translational and clinical programs in stem cell and regenerative medicine. In fact, the NHLBI has entered into a collaboration with CIRM on their Cure Sickle Cell initiative because of CIRM’s specialization in funding and enabling cell-gene regenerative medicine research.  I take this as a validation of CIRM’s value proposition in this new area– acceleration, translation, and clinical trials.

Q: Given the visibility being given to stem cell tourism and direct to consumer marketing of unproven and unregulated therapies, what value does CIRM bring to patients?

A: CIRM is positioned as the trusted agency for delivering on high quality trials, for being on the side of patients for safe trials and treatments and is a credible partner for patient, industry, government stakeholders to tackle this issue of stem cell tourism. We only fund clinical trials backed by solid scientific data with FDA permission to test it in patients. We have funded research being conducted at top tier medical centers and created the Alpha Stem Cell Clinic Network to provide people with high quality clinical trials. We are remaining in close contact with our legislators, including Speaker Pro Tem Kevin Mullin, Chair of the Assembly Select Committee on Biotechnology, to evaluate potential ways to protect patients from illegitimate clinics while progress is being made with legitimate approaches.

Q: Do you feel that enough money is being put towards basic research?

A: If we had the budget to do so, we would like to be able to fund more discovery research as well as translational and clinical research.  However, approximately $880M CIRM funds have gone into basic research thus far.  CIRM has a specialized and very unique role that supports and fosters rigorous stem cell and regenerative medicine science but, CIRM has distinguished itself as an agency that specializes in accelerating the translation of this science to therapies for patients.

Dr. Millan also appeared with SF Chronicle reporter Erin Allday and UC Davis stem cell scientist Paul Knoepfler on a Facebook Live talk about the work of the stem cell agency.

Stem cell stories that caught our eye: Reprogramming cells in vivo may help heal ulcers, CIRM-funded clinical trial shows promise and a New report, clears up an old question.

Stem cell image of the week:  New Research out of the Salk Institute could bring us closer to reprogramming stem cells without taking them out of the body (Adonica Shaw)

Our stem cell image of the week could be a step towards reprogramming cells in vivo.

The image represents the first proof of principle for the successful regeneration of a functional organ (the skin) inside a mammal, by a technique known as AAV-based in vivo reprogramming. Epithelial (skin) tissues were generated by converting one cell type (red: mesenchymal cells) to another (green: basal keratinocytes) within a large ulcer in a laboratory mouse model.


Photo courtesy of the Salk Institute

In large patches of ulcerous skin, surviving cells prioritize inflammation and wound closure. That’s what they’re programmed to do. Cells, on the other hand, can be reprogrammed in living tissue, wounded tissue, to expedite healing.

A group of scientists at the Salk Institute developed a new approach to cellular reprogramming. They found a way to directly convert the cells in an open wound into new skin cells. Their findings were published on Wednesday in Nature.

Reprogramming wound-resident cells could be useful for healing skin damage, countering the effects of aging, and helping us to better understand skin cancer. It could also supplant plastic surgery and the application of skin grafts as a way to treat large cutaneous ulcers, including those seen in people with severe burns, bedsores, or chronic diseases such as diabetes.

When an ulcer is especially large, it can be difficult for surgeons to graft enough skin. In these cases, researchers can isolate skin stem cells from a patient, grow them in the lab and transplant them back into the patient. However, such a procedure requires an extensive amount of time, which may put the patient’s life at risk and is sometimes not effective.

 “Our observations constitute an initial proof of principle for in vivo regeneration of an entire three-dimensional tissue like the skin, not just individual cell types as previously shown,” says Dr. Izpisua Belmonte. “This knowledge might not only be useful for enhancing skin repair but could also serve to guide in vivo regenerative strategies in other human pathological situations, as well as during aging, in which tissue repair is impaired.”

Positive news from a CIRM-funded clinical trial targeting a deadly blood cancer. (Kevin McCormack)  Multiple myeloma is a type of blood cancer where certain cells in the bone marrow grow out of control, crowding out the healthy cells and forming tumors. There is no cure but there are many treatments that can slow down or even halt the progression. Over time, however, many of those treatments lose their effectiveness and the cancer returns. Now a new CIRM-funded clinical trial targeting this kind of relapsing multiple myeloma is showing promise.

The trial, by Poseida Therapeutics, takes an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells. This product, called P-BCMA-101, is a stem cell memory chimeric antigen receptor T-cell (CAR-T).

In the first eleven patients treated there were no serious side effects and only one patient had a suspected case of cytokine release syndrome. That’s where large amounts of cytokines, immune substances, are rapidly released into the body causing fever, nausea, rapid heartbeat etc. However, even in this patient the symptoms quickly passed.

In a news release, Eric Ostertag, the CEO of Poseida said that even though the goal of this Phase 1 study was just to make sure it was safe and to identify the best dose to give patients, they have already seen a very good partial response in some patients.

“We believe our advantages of a purified product, where all cells express the CAR molecule, and a product with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a significantly better therapeutic index when compared with other CAR-T therapeutics. We are also encouraged that P-BCMA-101 is demonstrating significant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T therapies and that our response rates continue to improve as the dose increases.”

The clinical trial will eventually treat 40 patients with relapsing or remitting multiple myeloma and we will bring more results as they become available.

Techniques used in ecology help rewrite basic fact about blood stem cells (Todd Dubnicoff) It’s been over half a century since the first blood stem cell transplantation was performed. And yet, some fundamental facts about these cells – which give rise to all the cell types of our blood – have remained cloudy, like the number of blood stem cells present in the human body. This week, researchers at Wellcome Sanger Institute and Wellcome – MRC Cambridge Stem Cell Institute report that they’ve cleared up this long-lasting question.


A blood cell colony grown from a single cell isolated from a 59-year-old man. Image Credit: Mairi Shepherd, Kent Lab

And the results were surprising. Using whole genome DNA sequencing and techniques found in ecology for tracking population sizes, the team determined that a healthy adult has between 50,000 and 200,000 blood stem cells at any given time. That’s about 10 times more than what was previously thought.

Dr. David Kent, a co-senior author on the report, described the implications of this discovery in a press release:

“This new approach is hugely flexible. Not only can we measure how many stem cells exist, we can also see how related they are to each other and what types of blood cells they produce. Applying this technique to samples from patients with blood cancers, we should now be able to learn how single cells outcompete normal cells to expand their numbers and drive a cancer.”

The study was published in Nature.





How Blockchain Can Increase Accessibility to Stem Cell Therapy


Photo courtesy of BTCManager

The revolution has arrived. Believe it or not, we are living in a world where artificial intelligence, virtual reality, and stem cell therapies are no longer concepts of science fiction, but are realities of our everyday life. While the development of these things may appear to be in their infancy, it’s undoubtedly true that they each hold a unique opportunity for science to unlock cures to diseases like ALS, Sickle Cell disease, Alzheimer’s and Duchenne’s Muscular Dystrophy.

What is equally true however, is despite the fact that these opportunities are on the horizon, on a global scale there are still significant barriers to accessing clinical trials and quality medical care.

So how do we address this?

Well, according to a company called Stem Cell Project – we need to get creative.

This new Japan-based company set out to create the blockchain-enabled Virtual Clinic, fully equipped with AI technology, diagnostic tools, and its own native currency, the Stem Cell Coin.

 Issues with Modern Healthcare

Modern healthcare has developed rapidly in the past few decades, but is not without its drawbacks. For many people there’s a degree of difficulty in gaining access to qualified specialists. When you consider basic factors like distance and skill shortage, or larger issues like the lack of universal healthcare, it means the average person is unable to afford the high cost of preventative medical treatments, leading to more than 45,000 deaths per year in the United States alone.

In many first-world countries, birth rates have declined over the decades whilst the general population has continued to age. Not only has this has increased the need for specialists in fields treating diseases of aging, like Cancer and Alzheimer’s, but it also means we need to accelerate our efforts to keep up with the growing population.

Using Blockchain to Access Health Records

While many hear the word blockchain and think of cryptocurrencies, it also allows for an ultra-secure means by which patients can interact with healthcare professionals without worrying if malicious third-parties can access their most sensitive personal data. It is for this reason that Stem Cell Project decided to use the groundbreaking technology in their Virtual Clinic.

“Patients are increasingly aware of how their data is being used and who is allowed to access it,” explained Stem Cell Project’s founder Shuji Yamaguchi in a news release. “We therefore wanted to find a solution that was highly secure. Having a patient’s trust is, in many ways, the first step to mass adoption for Stem Cell Coin.”

Beyond that, the platform also ensures patients have access to a decentralized and unchangeable health record. Something which to date has never been fully implemented by a large-scale healthcare organization such as the one backing Stem Cell Project.

Opening the Path to Healthcare Equality

As Stem Cell Coin’s vision continues to be rolled out, a number of complementary applications will also be developed to support the Virtual Clinic. Among these, digital initiatives such as pathological and diagnostic imaging systems have the potential to further build upon the notion of a decentralized, universally-accessible healthcare ecosystem.  Moreover, the ability to pay for stem cell treatment via Stem Cell Coin will allow people to pay and travel for therapy regardless of whether their country exerts strict capital controls. The best example of this is China, where even its wealthy citizens are unable to travel to places like the United States of America and Europe for treatment, as the current cost for stem cell therapy ($10,000 – $50,000) exceeds the limits imposed by their government on how much Yuan can be taken abroad.

Counterfeit drugs and treatments could become easier to spot:

Based on reports from the World Health Organization (WHO), the value of the counterfeit drug market is $200 billion annually. In fact, they estimate 80% of the counterfeit drugs that are consumed in the United States come from overseas. Furthermore – they believe that 16% of counterfeit drugs contain the wrong ingredients, and 17% contain the wrong levels of necessarily ingredients. Not only does this undermine the research and scientists, who are actively looking for treatments by following an established protocol, but the financial burden families and patients are enduring to have access to these drugs is considerably high – especially given that WHO reports that 30% of the counterfeit drugs that are available don’t contain any active ingredients whatsoever. A blockchain-based system would ensure a chain-of-custody log, tracking each step of the supply chain at the individual drug/product level.

Results from clinical trials could become more transparent:

It is estimated that 50% of clinical trials go unreported, and investigators often fail to share their study results. This has created crucial safety issues for patients and knowledge gaps for healthcare stakeholders and health policymakers. Some say, blockchain-enabled, time-stamped immutable records of clinical trials, protocols and results could address the issues of fraudulent outcome reporting, data snooping and selective reporting, thereby reducing the incidence of fraud and error in clinical trial records. Furthermore, blockchain-based systems could help drive unprecedented collaboration between participants and researchers for innovative research projects.

 As new projects such as Stem Cell Coin are able to increase access to regenerative medicine, not only will distance or income cease to determine health outcomes, but we might even be able to address other issues plaguing the healthcare industry.




3D printed neuronal networks are an important step forward in treating spinal cord injury

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3D printed live neuronal cells. Image courtesy of the University of Minnesota.

Approximately 300,000 people in the United States live with spinal cord injury (SCI), and 17,000 new cases are reported every year. With no cure, the primary treatment option for people with SCI is rehabilitation with a physical therapist combined with medications to control the pain. Given the relatively permanent nature of these injuries, a new study conducted by Dr. Michael McAlpine and Dr. Ann Parr’s groups at the University of Minnesota is particularly exciting. These scientists have developed a 3D-printing technique to generate a network of neuronal cells in the lab, which they hope will be useful to treat patients with long term SCI. This is the first instance of printing and differentiating neuronal stem cells in a lab. Let’s take a look at how they did it!

The investigators started with induced pluripotent stem cells derived from adult cells (ex. blood, skin etc…), which were then used to bioprint the neurons of interest. They not only printed neurons, but also neuronal support cells called oligodendrocytes, which are responsible for ensuring that neurons can transmit messages efficiently. The uniqueness of their approach lies in their printing process, where the cells were printed in the context of a silicone mold. The silicone “guide” promoted neuronal differentiation as well as provided a scaffold for the scientists to spatially organize the architecture of the cells they generated. Both spatial organization and the presence of the neuronal support cells is particularly important because previous studies have shown that while injecting rodents with neural stem cells has improved SCI, the longevity of these results was compromised by a lack of support system for the injected cells. Therefore, the ability to generate both a functional cell type as well as a spatially accurate structure is important to make this neuronal printing system relevant for treating patients.

To confirm that printed cells were functional, the investigators used calcium flux assays, which demonstrated that the neuronal networks generated were able to communicate with each other. Not only were the cells healthy and functional, but their viability was exceptional: 75% of the cells stayed alive, which is remarkable for cells printed in a laboratory.

While there is still a long way to go before this type of treatment can used to treat SCI in humans, the potential for helping people with long term spinal cord injury is significant. Dr. Parr states:

“We’ve found that relaying any signals across the injury could improve functions for the patients. There’s a perception that people with spinal cord injuries will only be happy if they can walk again. In reality, most want simple things like bladder control or to be able to stop uncontrollable movements of their legs. These simple improvements in function could greatly improve their lives.”

The possibility of implanted neuronal stem cells being effective to treat SCI is also being investigated with the CIRM-funded Asterias trial. To check out more information about this work, read our blog post here and the clinical trial details here.

Mustang Bio picks up CIRM supported ‘bubble boy’ gene therapy


SCID refers to a group of rare diseases caused by mutations in genes that play a role in the development and function of immune cells. (Darwin Laganzon)

When babies are born they’re somewhat protected from infections through antibodies that were transferred to them in the womb. However, as time passes and immune systems develop their bodies start to learn how to combat infections on their own. For some children this process is seamless, but for others, it can be a sensitive time when parents learn about immune problems that haven’t resolved normally in the first months of life.

For starters, the immune system has many parts and symptoms of immune deficiency can depend on what part of the immune system is affected. These deficiencies can range from mild to aggressive and even life-threatening. One example of a life-threatening immune problem is severe combined immunodeficiency (SCID). Last year a CIRM-funded clinical trial run by St. Jude Children’s Research Hospital and UC San Francisco saved the life of a little boy named Ronnie who suffered from SCID. Based on the success of this approach a company named Mustang Bio just licensed a gene therapy from St. Jude Children’s Research Hospital for X-linked severe combined immunodeficiency (X-SCID), also called “bubble boy” syndrome. This agreement adds a rare disease gene therapy to Mustang’s pipeline, which is focused on fighting various cancers using CAR-T treatments.


Photo Credit: Pawash Priyank of Ronnie Priyank

In most cases, unless SCID patients receive immune-restoring treatments—such as transplants of blood-forming stem cells, enzyme therapy, or gene therapy—the condition is fatal, usually in the first year or two of life, according to the National Institute of Allergy and Infectious Diseases.

St. Jude’s treatment entails administering a low dose of the cancer drug busulfan before reinfusing a patients with their own stem cells that have been gene-modified. It’s currently in a pair of Phase 1/2 trials in infants under age 2 and in children over the age of 2. Eight patients under 2 have been treated so far, with six of them “[achieving] reconstituted immune systems within three to four months following treatment,” according to the company.

“Our therapy has been well tolerated thus far, and none of the infants required any blood product support after low dose of busulfan,” said Ewelina Mamcarz, M.D., an assistant member at St. Jude who led the study, in a release. “Most importantly, we observe recovery of all cells of the immune system, which is truly an achievement over prior gene therapy trials, where B cell reconstitution did not occur, and patients required intravenous immunoglobulin for life.”

Mustang and St. Jude haven’t disclosed financial terms of their agreement. They believe there may be as many as 1,500 patients in the U.S. and a similar number in Europe with X-linked SCID for whom donor bone marrow or blood stem cell transplants simply aren’t enough. They feel these patients could be eligible for their lentiviral gene therapy.

“We are thrilled to announce the expansion of our pipeline into gene therapy for patients with X-SCID, a natural fit for our Worcester, Massachusetts, cell processing facility,” said Mustang CEO Manny Litchman, M.D., in a statement.

Mustang and St. Jude will advance the program through ongoing phase 1/2 trials, with the goal of providing long-term treatment to the more than 80% of infants who lack fully matched bone marrow transplant donors. Through their partnership they hope to help the small number of patients who continue to have significant impairment of immunity.

Join us for our next installment of “Ask The Stem Cell Team” on August 28th.

What do football, jazz and acting have in common? They all happen to be the greatest accomplishments of some of the well-known celebrities who suffer from, and who have been vocal advocates for, Sickle Cell disease (SCD). While most people wouldn’t readily identify Tiki Barber, Miles Davis or Larenz Tate as carriers of the HBB gene, all three have been in the public eye as of late, spreading awareness about their .

Sickle cell disease is caused by having two mutated copies of the hemoglobin (HBB) gene (one from mom and another from dad). A person with two copies of the S version of the HBB gene (S which is short for “sickle”) typically has SCD.

People with sickle cell trait typically do not have any symptoms of sickle cell disease, but can pass it on to their children. Additionally, more than 80,000 Americans have sickle cell disease and despite decades of research the average life expectancy has dropped from 42 in 1995 to 39 today. It is a disease that largely targets the African-American community – which is why our team decided It was necessary to discuss this debilitating disease.


This event will feature Mark Walters, a pediatric hematologist/oncologist from Children’s Hospital Oakland Research Institute, Don Kohn, Professor, Microbiology, Immunology and Molecular Genetics at UCLA, and Adrienne Shapiro, a patient advocate for SCD and the co-founder of the Axis Advocacy SCD patient education and support website.

Our Facebook Live event, “Ask the Stem Cell Team About Sickle Cell Disease” is– Tuesday, August 28th – from noon till 1pm PST. You can join us by logging on to our Facebook.

Also, make sure to “like” our FaceBook page before the event to receive a notification when we’ve gone live for this and future events.

We want to answer your most pressing questions, so please email them directly to us beforehand at

A recording of the session will be available in our FaceBook videos page shortly after the broadcast ends.

We hope to see you there.


New Study on Humans Shows Promise for Sepsis Therapy

A new study published in STEM CELLS, conducted by researchers at the University of Amsterdam, shows how mesenchymal stem cells (MSCs) can restore the health and improve the function of the immune system,  which could benefit the treatment of sepsis. Sepsis is a life-threatening complication from an infection that can lead to multiple organ failure. It is a major cause of illness and death worldwide and despite the use of antibiotics it kills about one in every four patients who contract it.

Since early studies done on animals have shown that treating sepsis with MSCs can reduce the mortality rate by as much as 73 percent, a group of researchers from University of Amsterdam sought to answer this question:  could humans realize the same benefits?

So, the team conducted an experiment by taking a group of healthy volunteers and inducing endotoxemia in them, where bacterial toxins can build up and cause fever, nausea and vomiting but do not cause long-term harm to the participants (?).  The idea was that by inducing endotoxemia, which exhibits some of the key characteristics of sepsis, that they could model the condition in people.

One hour prior to the initial dose, each person was given an infusion of either adipose (fat) mesenchymal stem cells (ACSs) taken from a donor,  or a placebo as a control. Those receiving the ASCs were divided into three groups, with each group receiving a consecutively higher dose of cells.

In a news release, Desiree Perlee, senior author of the study, said the study provided some valuable insights and information:


Desirée Perlee

“The results showed that the ASCs were well tolerated…We realize that there is a limitation with the endotoxemia model. Although in a qualitative way it resembles responses seen in patients with sepsis, it differs in that sepsis-associated alterations are more severe and sustained, while in the endotoxemia model responses occur in a very rapid, short-lived and transient way. But despite these limitations, some of our findings confirm the earlier studies on animals. We believe they show further testing of ASCs in actual sepsis patients is warranted.”

Dr. Jan Nolta, Editor-in-Chief of STEM CELLS (and a CIRM-grantee), said, “This novel clinical trial provides important insight into the mechanism of action of MSCs in inflammation and provides human safety data in support of treatment of sepsis using MSCs.


Blood stem cell expansion expands treatment options for cancer patients

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Image courtesy of the Stower’s Institute

Bone marrow transplants have been used for decades to treat various types of cancers such as leukemia and multiple myeloma, as well as other blood disorders such as anemia.

Our bone marrow is responsible for making hematopoietic stem cells (HSCs), which develop into mature blood cells, like white cells (which fight infection) and red cells (which carry oxygen throughout our body). In different types of blood disorders, blood cell production is either impaired or abnormal. In leukemia for example, the body produces abnormal white blood cells that survive better then outgrow the normal white cells, thus impairing the individual’s ability to fight infection. Bone marrow transplants, which involves replacing the diseased marrow with healthy marrow from a donor, can be incredibly effective for these types of disease. Survival from certain blood cancers increased from basically zero to around eighty-five percent after the advent of bone marrow transplant therapy.

While extremely effective when successful, bone marrow transplants do not work for everyone and finding a match can be difficult. For example, only 30% of patients are able to find a match in their families, because of the strict requirements that must be fulfilled be a bone marrow match. Stem cells from umbilical cord blood, on the other hand, are much more likely to match a patient, because of the generally less stringent requirements to be a match. The amount of cord blood (nearly two whole cords worth of blood) needed to satisfy an adult patient’s transplant requirements, however, are significant, and can be a limiting factor in the efficiency and effectiveness of this approach. New research from Lingheng Li’s lab at the Stower’s Institute for Medical Research at the University of Kansas has found a possible solution to this problem.

In a study published in Cell Research, Li’s group found a way to increase the number of adult stem cells isolated from cord blood, which could reduce the number of cords needed per treatment. By eliminating a protein called Ythdf2 in mice, they observed global expansion of HSCs. Normally, this protein is responsible for preventing expression of genes involved in promoting HSC expansion. Importantly, the researchers found that the HSC expansion stimulated by elimination of Ythdf2 did not lead to other abnormalities in the resulting HSCs and did not affect the ability of these HSCs to produce different types of blood stem cells down the road. Dr. Li believes that this type of approach can be applied to other types of stem cell treatments as well.

Dr. Joseph McGuirk, another professor at the University of Kansas who was not directly involved with this study, indicates the importance of this work:

“This work represents a path forward by demonstrating the ability to reliably expand adult stem cells from umbilical cord blood in the laboratory without terminally differentiating the cells into more mature and relatively short-lived blood cells. These findings represent a major advance in the field and have significant potential to improve the outcomes of thousands of children and adults who undergo umbilical cord blood transplantation every year.”

CIRM is funding work in this area too. We are supporting a late stage preclinical project with AngioCrine Biosciences which is using expanded cord blood stem cells. They hope to create an effective and, safe option for the treatment of debilitating blood diseases such as leukemia and lymphoma.