USC study shows how tumor cells in the bloodstream can target distant organs

Various types of cancer can become particularly aggressive and difficult to treat once they spread from their initial point of origin to other parts of the body. This unfortunate phenomenon, known as metastasis, can make treatment very challenging, decreasing the chance of survival for the patient.

In order to better understand this process, a CIRM supported study at USC looked at breast cancer cells circulating in the blood that eventually invade the brain. The findings, which appear in Cancer Discovery, shed light on how tumor cells in the blood are able to target a particular organ, which may enable the development of treatments than can prevent metastasis from occurring.

Dr. Min Yu

Dr. Min Yu and her lab at USC were able to isolate breast cancer cells from the blood of breast cancer patients whose cancer had already metastasized. The team then expanded the number of cancer cells through a process known as cell culture. These expanded human tumor cells were then injected into the bloodstream of animal models. It was found that these cells migrated to the brain as was predicted.

Upon further analysis, Dr. Yu and her lab discovered a protein on the surface of the tumor cells in the bloodstream that enable them to breach the blood brain barrier, a protective layer around the brain that blocks the passage of certain substances, and enter the brain. Additionally, Dr. Yu and her team discovered another protein inside the tumor cells that shield them from the brain’s immune response, enabling these cells to grow inside the brain.

In a news release in Science Magazine, Dr. Yu talks about how these findings could be used to improve treatment and prevention options for those with aggressive cancers:

“We can imagine someday using the information carried by circulating tumor cells to improve the detection, monitoring and treatment of the spreading cancers. A future therapeutic goal is to develop drugs that get rid of circulating tumor cells or target those molecular signatures to prevent the spread of cancer.”

CIRM has also funded a separate clinical trial related to the treatment of breast cancer related brain metastases.

Predicting the Impact of Stem Cell Cures on Healthcare Burden in California

A new independent report says developing stem cell treatments and cures for some of the most common and deadly diseases could produce multi-billion dollar benefits for California in reduced healthcare costs and improved quality and quantity of life.

The report, by researchers at the University of Southern California’s Leonard D. Schaeffer Center for Health Policy & Economics, looked at the value of hypothetical future interventions to reduce or cure cancer, diabetes, stroke and blindness.

Predicting the future is always complicated and uncertain and many groups are looking at the best models to determine the value and economic impact of cell and gene therapy as the first products are just entering the market. This study provides some insights into the potential financial benefits of developing effective stem cell treatments for some of the most intractable diseases affecting California today.

The impact could affect millions of people. In 2018 for Californians over the age of 50:

  • Nearly half were predicted to develop diabetes in their lifetime
  • More than one third will experience a stroke
  • Between 5 and 8 percent will develop either breast, colorectal, lung, or prostate cancer

The report says that a therapy that decreased the incidence of diabetes by 50 percent in Californians over the age of 51 would translate into a gain for the state of $322 billion in social value between now and 2050. Even just reducing diabetes 10% would lead to a gain of $60 billion in social value over the same period.

  • For stroke a 50 percent reduction would generate an estimated $229 billion in social value. A 10 percent reduction would generate $47 billion
  • For breast cancer a 50 percent reduction would generate $56 billion in social value; for colorectal cancer it would be $72 billion; for lung cancer $151 billion; and prostate cancer $53 billion. 

The impact of a cure for any one of those diseases would be enormous. For example, a 51-year-old woman cured of lung cancer could expect to gain a lifetime social value of almost half a million dollars ($467,275). That’s a measure of years of healthy life gained, of years spent enjoying time with family and friends and not wasting away or lying in a hospital bed.

The researchers say: “Though advances in scientific research defy easy predictions, investing in biomedical research is important if we want to reduce the burden of common and costly diseases for individuals, their families, and society. These findings show the value and impact breakthrough treatments could have for California.”

“Put in this context, the CIRM investment would be worthwhile if it increased our chances of success even modestly. Against the billions of dollars in disease burden facing California, the relatively small initial investment is already paying dividends as researchers work to bring new therapies to patients.”

The researchers determined the “social value” using a measure called a quality adjusted life-year (QALY). This is a way of estimating the cost effectiveness and consequences of treating or not treating a disease. For example, one QALY is equivalent to one year of perfect health for an individual. In this study the value of that year was estimated at $150,000. If someone is sick with, say, diabetes, their health would be estimated to be 0.5 QALY or $75,000. So, the better health a person enjoys and the longer they enjoy it the higher QALY score they accumulate. In the case of a disease affecting millions of people in that state or country that can obviously lead to very large QALY scores representing potentially billions of dollars.

New Report Says CIRM Produces Big Economic Boost for California

An independent Economic Impact Report says the California Institute for Regenerative Medicine (CIRM) has had a major impact on California’s economy, creating tens of thousands of new jobs, generating hundreds of millions of dollars in new taxes, and producing billions of dollars in additional revenue for the state.

The report, done by Dan Wei and Adam Rose at the Price School of Public Policy at the University of Southern California, looked at the impacts of CIRM funding on both the state and national economy from the start of the Stem Cell Agency in 2004 to the end of 2018.

The total impacts on the California economy are estimated to be:

  • $10.7 billion of additional gross output (sales revenue)
  • $641.3 million of additional state/local tax revenues
  • $726.6 million of additional federal tax revenues
  • 56,549 additional full-time equivalent (FTE) jobs, half of which offer salaries considerably higher than the state average

Maria Millan, M.D., CIRM’s President and CEO, says the report reflects the Agency’s role in building an ecosystem to accelerate the translation of important stem cell science to solutions for patients with unmet medical needs. “CIRM’s mission on behalf of patients has been the priority from day one, but this report shows that CIRM funding brings additional benefits to the state. This report reflects how CIRM is promoting economic growth in California by attracting scientific talent and additional capital, and by creating an environment that supports the development of businesses and commercial enterprises in the state”

In addition to the benefits to California, the impacts outside of California on the US economy are estimated to be:

  • $4.7 billion of additional gross output (sales revenue)
  • $198.7 million of additional state (non-Californian) & local tax revenue
  • $208.6 million of additional federal tax revenues
  • 25,816 additional full-time equivalent (FTE) jobs

The researchers summarize their findings, saying: “In terms of economic impacts, the state’s investment in CIRM has paid handsome dividends in terms of output, employment, and tax revenues for California.”

The estimates in the report are based on the economic stimulus created by CIRM funding and by the co-funding that researchers and companies were required to provide for clinical and late-stage preclinical projects. The estimates also include:

  • Investments in CIRM-supported projects from private funders such as equity investments, public offerings and mergers and acquisitions,
  • Follow-on funding from the National Institutes of Health and other organizations due to data generated in CIRM-funded projects
  • Funding generated by clinical trials held at CIRM’s Alpha Stem Cell Clinics network

The researchers state “Nearly half of these impacts emanate from the $2.67 billion CIRM grants themselves.”

“The economic impact of California’s investment in stem and regenerative cell research is reflective of significant progress in this field that was just being born at the time of CIRM’s creation,” says Dr. Millan. “We fund the most promising projects based on rigorous science from basic research into clinical trials. We partnered with researchers and companies to increase the likelihood of success and created specialized infrastructure such as the Alpha Clinics Network to support the highest quality of clinical care and research standards for these novel approaches.  The ecosystem created by CIRM has attracted scientists, companies and capital from outside the state to California. By supporting promising science projects early on, long before most investors were ready to come aboard, we enabled our scientists to make progress that positioned them to attract significant commercial investments into their programs and into California.”

These partnerships have helped move promising therapies out of the lab and into clinical trials for companies like Orchard Therapeutics’ successful treatment for Severe Combined Immunodeficiency and Forty Seven Inc.’s innovative approach to treating cancer.

Dr. Don Kohn: Photo courtesy UCLA Jonsson Comprehensive Cancer Center

“I think one of the greatest strengths of CIRM has been their focus on development of new stem cell therapies that can become real medicines,” says UCLA and Orchard Therapeutics’ Don Kohn, M.D. “This has meant guiding academic investigators to do the things that may be second nature in industry/pharmaceutical companies but are not standard for basic or clinical research.  The support from CIRM to perform the studies and regulatory activities needed to navigate therapies through the FDA and to form alliances with biotech and pharma companies has allowed the stem cell gene therapy we developed to treat SCID babies to be advanced and licensed to Orchard Therapeutics who can make it available to patients across the country.”

Dr. Mark Chao: Photo courtesy Forty Seven Inc.

“CIRM’s support has been instrumental to our early successes and our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach with magrolimab,” says Mark Chao, M.D., Ph.D., Founder and Vice President of Clinical Development at Forty Seven Inc. “ CIRM was an early collaborator in our clinical programs, and will continue to be a valued partner as we move forward with our MDS/AML clinical trials.”

The researchers say the money generated by partnerships and investments, what is called “deal-flow funding”, is still growing and that the economic benefits created by them are likely to continue for some time: “Deal-flow funding usually involves several waves or rounds of capital infusion over many years, and thus is it expected that CIRM’s past and current funding will attract increasing amounts of industry investment and lead to additional spending injections into the California economy in the years to come.”

They conclude their report by saying: “CIRM has led to California stem cell research and development activities becoming a leader among the states.”

CIRM Board Approves $19.7 Million in Awards for Translational Research Program

In addition to approving funding for breast cancer related brain metastases last week, the CIRM Board also approved an additional $19.7 million geared towards our translational research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

Before getting into the details of each project, here is a table with a brief synopsis of the awards:

TRAN1 – 11532

Illustration of a healthy eye vs eye with AMD

$3.73 million was awarded to Dr. Mark Humayun at USC to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD).

AMD is an eye disease that causes severe vision impairment, resulting in the inability to read, drive, recognize faces, and blindness if left untreated.  It is the leading cause of vision loss in the U.S. and currently affects over 2 million Americans.  By the year 2050, it is projected that the number of affected individuals will more than double to over 5 million.  A layer of cells in the back of the eye called the retinal pigment epithelium (RPE) provide support to photoreceptors (PRs), specialized cells that play an important role in our ability to process images.  The dysfunction and/or loss of RPE cells plays a critical role in the loss of PRs and hence the vision problems observed in AMD.  One form of AMD is known as dry AMD (dAMD) and accounts for about 90% of all AMD cases.

The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dAMD, supporting the survival of photoreceptors in the affected retina.

TRAN1 – 11579

Illustration depicting the role neuronal relays play in muscle sensation

$6.23 million was awarded to Dr. Mark Tuszynski at UCSD to develop a neural stem cell therapy for spinal cord injury (SCI).

According to data from the National Spinal Cord Injury Statistical Center, as of 2018, SCI affects an estimated 288,000 people in the United States alone, with about 17,700 new cases each year. There are currently no effective therapies for SCI. Many people suffer SCI in early adulthood, leading to life-long disability and suffering, extensive treatment needs and extremely high lifetime costs of health care.

The approach that Dr. Tuszynski is developing will use hESCs to create neural stem cells (NSCs).  These newly created NSCs would then be grafted at the site of injury of those with SCI.  In preclinical studies, the NSCs have been shown to support the formation of neuronal relays at the site of SCI.  The neuronal relays allow the sensory neurons in the brain to communicate with the motor neurons in the spinal cord to re-establish muscle control and movement.

TRAN1 – 11548

Graphic depicting the challenges of traumatic brain injury (TBI)

$4.83 million was awarded to Dr. Brian Cummings at UC Irvine to develop a neural stem cell therapy for traumatic brain injury (TBI).

TBI is caused by a bump, blow, or jolt to the head that disrupts the normal function of the brain, resulting in emotional, mental, movement, and memory problems. There are 1.7 million people in the United States experiencing a TBI that leads to hospitalization each year. Since there are no effective treatments, TBI is one of the most critical unmet medical needs based on the total number of those affected and on a cost basis.

The approach that Dr. Cummings is developing will also use hESCs to create NSCs.  These newly created NSCs would be integrated with injured tissue in patients and have the ability to turn into the three main cell types in the brain; neurons, astrocytes, and oligodendrocytes.  This would allow for TBI patients to potentially see improvements in issues related to memory, movement, and anxiety, increasing independence and lessening patient care needs.

TRAN1 – 11628

Illustration depicting the brain damage that occurs under hypoxic-ischemic conditions

$4.96 million was awarded to Dr. Evan Snyder at Sanford Burnham Prebys to develop a neural stem cell therapy for perinatal hypoxic-ischemic brain injury (HII).

HII occurs when there is a lack of oxygen flow to the brain.  A newborn infant’s body can compensate for brief periods of depleted oxygen, but if this lasts too long, brain tissue is destroyed, which can cause many issues such as developmental delay and motor impairment.  Current treatment for this condition is whole-body hypothermia (HT), which consists of significantly reducing body temperature to interrupt brain injury.  However, this is not very effective in severe cases of HII. 

The approach that Dr. Snyder is developing will use an established neural stem cell (NSC) line.   These NSCs would be injected and potentially used alongside HT treatment to increase protection from brain injury.

Taking the message to the people: fighting for the future of stem cell research in California

Stem cells have been in the news a lot this week, and not necessarily for the right reason.

First, the US Food and Drug Administration (FDA) won a big legal decision in its fight to crack down on clinics offering bogus, unproven and unapproved stem cell therapies.

But then came news that another big name celebrity, in this case Star Trek star William Shatner, was going to one of these clinics for an infusion of what he called “restorative cells”.

It’s a reminder that for every step forward we take in trying to educate the public about the dangers of clinics offering unproven therapies, we often take another step back when a celebrity essentially endorses the idea.

So that’s why we are taking our message directly to the people, as often as we can and wherever we can.

In June we are going to be holding a free, public event in Los Angeles to coincide with the opening of the International Society for Stem Cell Research’s Annual Conference, the biggest event on the global stem cell calendar. There’s still time to register for that by the way. The event is from 6-7pm on Tuesday, June 25th in Petree Hall C., at the Los Angeles Convention Center at 1201 South Figueroa Street, LA 90015.

The event is open to everyone and it’s FREE. We have created an Eventbrite page where you can get all the details and RSVP if you are coming.

It’s going to be an opportunity to learn about the real progress being made in stem cell research, thanks in no small part to CIRM’s funding. We’re honored to be joined by UCLA’s Dr. Don Kohn, who has helped cure dozens of children born with a fatal immune system disorder called severe combined immunodeficiency, also known as “bubble baby disease”. And we’ll hear from the family of one of those children whose life he helped save.

And because CIRM is due to run out of money to fund new projects by the end of this year you’ll also learn about the very real concerns we have about the future of stem cell research in California and what can be done to address those concerns. It promises to be a fascinating evening.

But that’s not all. Our partners at USC will be holding another public event on stem cell research, on Wednesday June 26th from 6.30p to 8pm. This one is focused on treatments for age-related blindness. This features some of the top stem cell scientists in the field who are making encouraging progress in not just slowing down vision loss, but in some cases even reversing it.

You can find out more about that event here.

We know that we face some serious challenges in trying to educate people about the risks of going to a clinic offering unproven therapies. But we also know we have a great story to tell, one that shows how we are already changing lives and saving lives, and that with the support of the people of California we’ll do even more in the years to come.

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

HIV AIDS

While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

Jeff Sheehy

CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

Children’s Hospital of Los Angeles $1,297,512

 

DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

barbara_lee_official_photo

Congresswoman Barbara Lee (D-CA 13th District)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

$93 million

$30 million

TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K

 

 

Hits and Myths as people celebrate Stem Cell Awareness Day

UC Davis #1

Stem Cell Awareness Day at UC Davis

Every year, the second Wednesday in October is set aside as Stem Cell Awareness Day, a time to celebrate the progress being made in the field and to remind us of the challenges that lie ahead.

While the event began here in California in 2008, with then-Governor Arnold Schwarzenegger highlighting the work of CIRM, saying: ”The discoveries being made today in our Golden State will have a great impact on many around the world for generations to come.” It has since grown to become a global event.

Here in California, for example, UC Davis and the University of Southern California (USC) both held events to mark the day.

At UC Davis Jan Nolta, PhD., the Director of the Stem Cell Program, introduced a series of speakers who highlighted the terrific work being done at the university. Peter Belafsky talked about using stem cells to repair damaged trachea and to help people who are experiencing voice or swallowing disorders. Mark Lee highlighted the progress being made in using stem cells to repair hard-to-heal broken bones. Aijun Wang focused on some really exciting work that could one day lead to a therapy for spina bifida (including some ridiculously cute video of English bulldogs who are able to walk again because of this therapy.)

USC hosted 100 local high school students for a panel presentation and discussion about careers in stem cell research. The panel featured four scientists talking about their experience, why the students should think about a career in science and how to go about planning one. USC put together a terrific video of the researchers talking about their experiences, something that can help any student around the US consider becoming part of the future of stem cell research.

Similar events were held in other institutions around California. But the celebration wasn’t limited to the Golden State. At the Texas Heart Institute in Houston, Texas, they held an event to talk to the public about the clinical trials they are supporting using stem cells to help people suffering from heart failure or other heart-related issues.

RegMedNet

Finally, the UK-based RegMedNet, a community site that unites the diverse regenerative medicine community, marked the day by exploring some of the myths and misconceptions still surrounding stem cells and stem cell research.

You can read those here.

Every group takes a different approach to celebrating Stem Cell Awareness Day, but each is united by a common desire, to help people understand the progress being made in finding new treatments and even cures for people with unmet medical needs.

The moment of truth. A video about the stem cell therapy that could help millions of people going blind.

“No matter how much one prepares, the first patient is always something very special.” That’s how Dr. Mark Humayun describes his feelings as he prepared to deliver a CIRM-funded stem cell therapy to help someone going blind from dry age-related macular degeneration (AMD).

Humayun, an ophthalmologist and stem cell researcher at USC, spent years developing this therapy and so it’s understandable that he might be a little nervous finally getting a chance to see if it works in people.

It’s quite a complicated procedure, involving turning embryonic stem cells into the kind of cells that are destroyed by AMD, placing those cells onto a specially developed synthetic scaffold and then surgically implanting the cells and scaffold onto the back of the eye.

There’s a real need for a treatment for AMD, the leading cause of vision loss in the US. Right now, there is no effective therapy for AMD and some three million Americans are facing the prospect of losing their eyesight.

The first, preliminary, results of this trial were released last week and they were encouraging. You can read about them on our blog.

Thanks to USC you can also see the team that developed and executed this promising approach. They created a video capturing the moment the team were finally taking all that hard work and delivering it where it matters, to the patient.

Watching the video it’s hard not to think you are watching a piece of history, something that has the potential to do more than just offer hope to people losing their vision, it has the potential to stop and even reverse that process.

The video is a salute to the researchers who developed the therapy, and the doctors, nurses and Operating Room team who delivered it. It’s also a salute to the person lying down, the patient who volunteered to be the first to try this. Everyone in that room is a pioneer.

A shot in the arm for people with bad knees

knee

Almost every day I get an email or phone call from someone asking if we have a stem cell therapy for bad knees. The inquiries are from people who’ve been told they need surgery to replace joints damaged by age and arthritis. They’re not alone. Every year around 600,000 Americans get a knee replacement. That number is expected to rise to three million by 2030.

Up till now my answer to those calls and emails has been ‘I’m sorry, we don’t have anything’. But a new CIRM-funded study from USC stem cell scientist Denis Evseenko says that may not always be the case.

JointCartilege_nancy_liu-824x549

The ability to regenerate joint cartilage cells instead of surgically replacing joints would be a big boon for future patients. (Photo/Nancy Liu, Denis Evseenko Lab, USC Stem Cell)

Evseenko and his team have discovered a molecule they have called Regulator of Cartilage Growth and Differentiation or RCGD 423. This cunning molecule works in two different ways. One is to reduce the inflammation that many people with arthritis have in their joints. The second is to help stimulate the regeneration of the cartilage destroyed by arthritis.

When they tested RCGD 423 in rats with damaged cartilage, the rats cartilage improved. The study is published in the Annals of Rheumatic Diseases.

In an article in USC News, Evseenko, says there is a lot of work to do but that this approach could ultimately help people with osteoarthritis or juvenile arthritis.

“The goal is to make an injectable therapy for an early to moderate level of arthritis. It’s not going to cure arthritis, but it will delay the progression of arthritis to the damaging stages when patients need joint replacements, which account for a million surgeries a year in the U.S.”

How mice and zebrafish are unlocking clues to repairing damaged hearts

Bee-Gees

The Bee Gees, pioneers in trying to find ways to mend a broken heart. Photograph: Michael Ochs Archives

This may be the first time that the Australian pop group the Bee Gees have ever been featured in a blog about stem cell research, but in this case I think it’s appropriate. One of the Bee Gees biggest hits was “How can you mend a broken heart” and while it was a fine song, Barry and Robin Gibb (who wrote the song) never really came up with a viable answer.

Happily some researchers at the University of Southern California may succeed where Barry and Robin failed. In a study, published in the journal Nature Genetics, the USC team identify a gene that may help regenerate damaged heart tissue after a heart attack.

When babies are born they have a lot of a heart muscle cell called a mononuclear diploid cardiomyocyte or MNDCM for short. This cell type has powerful regenerative properties and so is able to rebuild heart muscle. However, as we get older we have less and less MNDCMs. By the time most of us are at an age where we are most likely to have a heart attack we are also most likely to have very few of these cells, and so have a limited ability to repair the damage.

Michaela Patterson, and her colleagues at USC, set out to find ways to change that. They found that in some adult mice less than 2 percent of their heart cells were MNDCMs, while other mice had a much higher percentage, around 10 percent. Not surprisingly the mice with the higher percentage of MNDCMs were better able to regenerate heart muscle after a heart attack or other injury.

So the USC team – with a little help from CIRM funding – dug a little deeper and did a genome-wide association study of these mice, that’s where they look at all the genetic variants in different individuals to see if they can spot common traits. They found one gene, Tnni3k, that seems to play a key role in generating MNDCMs.

Turning Tnni3K off in mice resulted in higher numbers of MNDCMs, increasing their ability to regenerate heart muscle. But when they activated Tnni3k in zebrafish it reduced the number of MNDCMs and impaired the fish’s ability to repair heart damage.

While it’s a long way from identifying something interesting in mice and zebrafish to seeing if it can be used to help people, Henry Sucov, the senior author on the study, says these findings represent an important first step in that direction:

“The activity of this gene, Tnni3k, can be modulated by small molecules, which could be developed into prescription drugs in the future. These small molecules could change the composition of the heart over time to contain more of these regenerative cells. This could improve the potential for regeneration in adult hearts, as a preventative strategy for those who may be at risk for heart failure.”