University of Southern California

Stem cell-derived retinal patch continues to show promising results two years post-implantation

/ Katie Sharify / 3 Comments

Earlier this year we wrote about the promising results of a phase 1 clinical trial aimed at replacing the deteriorating cells in the retinas of people suffering from age-related macular degeneration- one of the leading causes of blindness worldwide for people over 50. Now there’s even more good news! Highlighted in a news story on the UC Santa Barbara (UCSB) website, researchers are continuing to make progress in their bid to secure approval from the Food and Drug Administration for the life-changing treatment.

Through the collaborative efforts of researchers at UCSB, University of Southern California and California Institute of Technology, a stem cell-derived implant using cells from a healthy donor was developed. The bioengineered implant, described as a scaffold, was then implanted under the retina of 16 participants. If the implant was to work, the new cells would then take up the functions of the old ones, and slow down or prevent further deterioration. In the best-case scenario, they could restore some lost vision.

The first sets of trials, funded by the California Institute for Regenerative Medicine (CIRM), concentrated on establishing the safety of the patch and collecting data on its effectiveness. Parting ways with old practices, the participants in the trial were given just two months of immunosuppressants whereas in the past, using donor cells meant that patients often had to be given long-term immunosuppression to stop their body’s immune system attacking and destroying the implanted cells. The team found that after two years, the presence of the patch hadn’t triggered other conditions associated with implantation, such as the formation of new blood vessels or scar tissue that could cause a detachment of the retina.

Even more importantly, they found no sign of inflammation that indicated an immune response to the foreign cells even after the patient was taken off immunosuppressants two months post-implantation. “What really makes us excited is that there is some strong evidence to show that the cells are still there two years after implantation and they’re still functional,” said Mohamed Faynus, a graduate student researcher in the lab of stem cell biologist Dennis O. Clegg at UCSB.

Having passed the initial phase, the team of researchers now hopes to begin phase 2 of the trial. This time, they are aiming to more specifically assesses the effectiveness of the patch in participants. Looking even farther ahead, the Clegg Lab and colleagues are also exploring combining multiple cell types on the patch to treat patients at varying stages of the disease.

In addition, there have also been improvements made to extend the shelf life of the patch. “Cryopreservation of the therapy significantly extends the product’s shelf-life and allows us to ship the implant on demand all over the world, thus making it more accessible to patients across the globe,” said Britney Pennington, a research scientist in the Clegg Lab.

Creating a diverse group of future scientists

/ Kevin McCormack / Leave a comment
Students in CIRM’s Bridges program showing posters of their work

If you have read the headlines lately, you’ll know that the COVID-19 pandemic is having a huge impact on the shipping industry. Container vessels are forced to sit out at anchor for a week or more because there just aren’t enough dock workers to unload the boats. It’s a simple rule of economics, you can have all the demand you want but if you don’t have the people to help deliver on the supply side, you are in trouble.

The same is true in regenerative medicine. The field is expanding rapidly and that’s creating a rising demand for skilled workers to help keep up. That doesn’t just mean scientists, but also technicians and other skilled individuals who can ensure that our ability to manufacture and deliver these new therapies is not slowed down.

That’s one of the reasons why CIRM has been a big supporter of training programs ever since we were created by the voters of California when they approved Proposition 71. And now we are kick-starting those programs again to ensure the field has all the talented workers it needs.

Last week the CIRM Board approved 18 programs, investing more than $86 million, as part of the Agency’s Research Training Grants program. The goal of the program is to create a diverse group of scientists with the knowledge and skill to lead effective stem cell research programs.

The awards provide up to $5 million per institution, for a maximum of 20 institutions, over five years, to support the training of predoctoral graduate students, postdoctoral trainees, and/or clinical trainees.

This is a revival of an earlier Research Training program that ran from 2006-2016 and trained 940 “CIRM Scholars” including:

• 321 PhD students
• 453 Postdocs
• 166 MDs

These grants went to academic institutions from UC Davis in Sacramento to UC San Diego down south and everywhere in-between. A 2013 survey of the students found that most went on to careers in the industry.

  • 56% continued to further training
  • 14% advanced to an academic research faculty position
  • 10.5% advanced to a biotech/industry position
  • 12% advanced to a non-research position such as teaching, medical practice, or foundation/government work

The Research Training Grants go to:

AWARDINSTITUTIONTITLEAMOUNT
EDUC4-12751Cedars-SinaiCIRM Training Program in Translational Regenerative Medicine    $4,999,333
EDUC4-12752UC RiversideTRANSCEND – Training Program to Advance Interdisciplinary Stem Cell Research, Education, and Workforce Diversity    $4,993,115
EDUC4-12753UC Los AngelesUCLA Training Program in Stem Cell Biology    $5 million
EDUC4-12756University of Southern CaliforniaTraining Program Bridging Stem Cell Research with Clinical Applications in Regenerative Medicine    $5 million
EDUC4-12759UC Santa CruzCIRM Training Program in Systems Biology of Stem Cells    $4,913,271
EDUC4-12766Gladstone Inst.CIRM Regenerative Medicine Research Training Program    $5 million
EDUC4-12772City of HopeResearch Training Program in Stem Cell Biology and Regenerative Medicine    $4,860,989
EDUC4-12782StanfordCIRM Scholar Training Program    $4,974,073
EDUC4-12790UC BerkeleyTraining the Next Generation of Biologists and Engineers for Regenerative Medicine    $4,954,238
EDUC4-12792UC DavisCIRM Cell and Gene Therapy Training Program 2.0    $4,966,300
EDUC4-12802Children’s Hospital of Los AngelesCIRM Training Program for Stem Cell and Regenerative Medicine Research    $4,999,500
EDUC4-12804UC San DiegoInterdisciplinary Stem Cell Training Grant at UCSD III    $4,992,446
EDUC4-12811ScrippsTraining Scholars in Regenerative Medicine and Stem Cell Research    $4,931,353
EDUC4-12812UC San FranciscoScholars Research Training Program in Regenerative Medicine, Gene Therapy, and Stem Cell Research    $5 million
EDUC4-12813Sanford BurnhamA Multidisciplinary Stem Cell Training Program at Sanford Burnham Prebys Institute, A Critical Component of the La Jolla Mesa Educational Network    $4,915,671  
EDUC4-12821UC Santa BarbaraCIRM Training Program in Stem Cell Biology and Engineering    $1,924,497
EDUC4-12822UC IrvineCIRM Scholars Comprehensive Research Training Program  $5 million
EDUC4-12837Lundquist Institute for Biomedical InnovationStem Cell Training Program at the Lundquist Institute    $4,999,999

These are not the only awards we make to support training the next generation of scientists. We also have our SPARK and Bridges to Stem Cell Research programs. The SPARK awards are for high school students, and the Bridges program for graduate or Master’s level students.

CIRM & CZI & MOU for COVID-19

/ Kevin McCormack / Leave a comment

Too many acronyms? Not to worry. It is all perfectly clear in the news release we just sent out about this.

A new collaboration between the California Institute for Regenerative Medicine (CIRM) and the Chan Zuckerberg Initiative (CZI) will advance scientific efforts to respond to the COVID-19 pandemic by collaborating on disseminating single-cell research that scientists can use to better understand the SARS-CoV-2 virus and help develop treatments and cures.

CIRM and CZI have signed a Memorandum of Understanding (MOU) that will combine CIRM’s infrastructure and data collection and analysis tools with CZI’s technology expertise. It will enable CIRM researchers studying COVID-19 to easily share their data with the broader research community via CZI’s cellxgene tool, which allows scientists to explore and visualize measurements of how the virus impacts cell function at a single-cell level. CZI recently launched a new version of cellxgene and is supporting the single-cell biology community by sharing COVID-19 data, compiled by the global Human Cell Atlas effort and other related efforts, in an interactive and scalable way.

“We are pleased to be able to enter into this partnership with CZI,” said Dr. Maria T. Millan, CIRM’s President & CEO. “This MOU will allow us to leverage our respective investments in genomics science in the fight against COVID-19. CIRM has a long-standing commitment to generation and sharing of sequencing and genomic data from a wide variety of projects. That’s why we created the CIRM genomics award and invested in the Stem Cell Hub at the University of California, Santa Cruz, which will process the large complex datasets in this collaboration.”  

“Quickly sharing scientific data about COVID-19 is vital for researchers to build on each other’s work and accelerate progress towards understanding and treating a complex disease,” said CZI Single-Cell Biology Program Officer Jonah Cool. “We’re excited to partner with CIRM to help more researchers efficiently share and analyze single-cell data through CZI’s cellxgene platform.”

In March 2020, the CIRM Board approved $5 million in emergency funding to target COVID-19. To date, CIRM has funded 17 projects, some of which are studying how the SARS-CoV-2 virus impacts cell function at the single-cell level.

Three of CIRM’s early-stage COVID-19 research projects will plan to participate in this collaborative partnership by sharing data and analysis on cellxgene.   

  • Dr. Evan Snyder and his team at Sanford Burnham Prebys Medical Discovery Institute are using induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids. These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treating the virus.
  • Dr. Brigitte Gomperts at UCLA is studying a lung organoid model made from human stem cells in order to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with COVID-19.
  • Dr. Justin Ichida at the University of Southern California is trying to determine if a drug called a kinase inhibitor can protect stem cells in the lungs and other organs, which the novel coronavirus selectively infects and kills.

“Cumulative data into how SARS-CoV-2 affects people is so powerful to fight the COVID-19 pandemic,” said Stephen Lin, PhD, the Senior CIRM Science Officer who helped develop the MOU. “We are grateful that the researchers are committed to sharing their genomic data with other researchers to help advance the field and improve our understanding of the virus.”

CZI also supports five distinct projects studying how COVID-19 progresses in patients at the level of individual cells and tissues. This work will generate some of the first single-cell biology datasets from donors infected by SARS-CoV-2 and provide critical insights into how the virus infects humans, which cell types are involved, and how the disease progresses. All data generated by these grants will quickly be made available to the scientific community via open access datasets and portals, including CZI’s cellxgene tool.

CIRM Board Approves Clinical Trials Targeting COVID-19 and Sickle Cell Disease

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Coronavirus particles, illustration.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.

Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.

This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.

“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”

The Board also approved two early stage research projects targeting COVID-19.

  • Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
  • Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.

“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”

The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients

SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy.  Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.

Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.

“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”

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

/ Kevin McCormack / 8 Comments

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)

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

 

 

A shot in the arm for people with bad knees

/ Kevin McCormack / 4 Comments

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.”

Translating great stem cell ideas into effective therapies

/ Kevin McCormack / Leave a comment

alzheimers

CIRM funds research trying to solve the Alzheimer’s puzzle

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

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

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

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

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

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

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

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

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

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

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

New approach could help turn back the clock and reverse damage for stroke patients

/ Kevin McCormack / 4 Comments

stroke

Stroke: courtesy WebMD

Stroke is the leading cause of serious, long-term disability in the US. Every year almost 800,000 people suffer from a stroke. The impact on their lives, and the lives of those around them can be devastating.

Right now the only treatment approved by the US Food and Drug Administration (FDA) is tissue plasminogen activator or tPA. This helps dissolve the blood clot causing most strokes and restores blood flow to the brain. However, to be fully effective this has to be administered within about 3-4 hours after the stroke. Many people are unable to get to the hospital in time and as a result suffer long-term damage, damage that for most people has been permanent.

But now a new study in Nature Medicine shows that might not be the case, and that this damage could even be reversible.

The research, done by a team at the University of Southern California (USC) uses a one-two punch combination of stem cells and a protein that helps those cells turn into neurons, the cells in the brain damaged by a stroke.

First, the researchers induced a stroke in mice and then transplanted human neural stem cells alongside the damaged brain tissue. They then added in a dose of the protein 3K3A-APC or a placebo.

hey found that mice treated with 3K3A-APC had 16 times more human stem-cell derived neurons than the mice treated with the placebo. Those neurons weren’t just sitting around doing nothing. USC’s Berislav Zlokovic, senior author of the paper, says they were actively repairing the stroke-induced damage.

“We showed that 3K3A-APC helps the grafted stem cells convert into neurons and make structural and functional connections with the host’s nervous system. No one in the stroke field has ever shown this, so I believe this is going to be the gold standard for future studies. Functional deficits after five weeks of stroke were minimized, and the mice were almost back to normal in terms of motor and sensorimotor functions. Synapses formed between transplanted cells and host cells, so there is functional activation and cooperation of transplanted cells in the host circuitry.”

The researchers wanted to make sure the transplanted cell-3K3A-ACP combination was really the cause of the improvement in the mice so they then used what’s called an “assassin toxin” to kill the neurons they had created. That reversed the improvements in the treated mice, leaving them comparable to the untreated mice. All this suggests the neurons had become an integral part of the mouse’s brain.

So how might this benefit people? You may remember that earlier this summer Stanford researchers produced a paper showing they had helped some 18 stroke patients, by injecting stem cells from donor bone marrow into their brain. The improvements were significant, including in at least one case regaining the ability to walk. We blogged about that work here

In that study, however, the cells did not become neurons nor did they seem to remain in the brain for an extended period. It’s hoped this new work can build on that by giving researchers an additional tool, the 3K3A-ACP protein, to help the transplanted cells convert to neurons and become integrated into the brain.

One of the other advantages of using this protein is that it has already been approved by the FDA for use in people who have experienced an ischemic stroke, which accounts for about 87 percent of all strokes.

The USC team now hope to get approval from the FDA to see if they can replicate their experiences in mice in people, through a Phase 2 clinical trial.

 

 

 

 

 

 

 

Stem cell stories that caught our eye: a surprising benefit of fasting, faster way to make iPSCs, unlocking the secret of leukemia cancer cells

/ Kevin McCormack / Leave a comment

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

Fasting

Is fasting the fountain of youth?

Among the many insults our bodies endure in old age is a weakened immune system which leaves the elderly more susceptible to infection. Chemotherapy patients also face the same predicament due to the immune suppressing effects of their toxic anticancer treatments. While many researchers aim to develop drugs or cell therapies to protect the immune system, a University of Southern California research report this week suggests an effective alternative intervention that’s startlingly straightforward: fasting for 72 hours.

The study published in Cell Stem Cell showed that cycles of prolonged fasting in older mice led to a decrease in white blood cells which in turn set off a regenerative burst of blood stem cells. This restart of the blood stem cells replenished the immune system with new white blood cells. In a pilot Phase 1 clinical trial, cancer patients who fasted 72 hours before receiving chemotherapy maintained normal levels of white blood cells.

A look at the molecular level of the process pointed to a decrease in the levels of a protein called PKA in stem cells during the fasting period. In a university press release carried by Science Daily, the study leader, Valter Longo, explained the significance of this finding:

“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the ‘okay’ for stem cells to go ahead and begin proliferating and rebuild the entire system. And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.”

In additional to necessary follow up studies, the team is looking into whether fasting could benefit other organ systems besides the immune system. If the data holds up, it could be that regular fasting or direct targeting of PKA could put us on the road to a much more graceful and healthier aging process.

4955224186_31f969e6fd_m

Faster, cheaper, safer way to use iPS cells

Science, like traffic in any major city, never moves quite as quickly as you would like, but now Japanese researchers are teaming up to develop a faster, and cheaper way of using iPSC’s , pluripotent stem cells that are reprogrammed from adult cells, for transplants.

Part of the beauty of iPSCs is that because those cells came from the patient themselves, there is less risk of rejection. But there are problems with this method. Taking adult cells and turning them into enough cells to treat someone can take a long time. It’s expensive too.

But now researchers at Kyoto University and three other institutions in Japan have announced they are teaming up to change that. They want to create a stockpile of iPSCs that are resistant to immunological rejection, and are ready to be shipped out to researchers.

Having a stockpile of ready-to-use iPSCs on hand means researchers won’t have to wait months to develop their own, so they can speed up their work.

Shinya Yamanaka, who developed the technique to create iPSCs and won the Nobel prize for his efforts, say there’s another advantage with this collaboration. In a news article on Nikkei’s Asian Review he said these cells will have been screened to make sure they don’t carry any potentially cancer-causing mutations.

“We will take all possible measures to look into the safety in each case, and we’ll give the green light once we’ve determined they are sound scientifically. If there is any concern at all, we will put a stop to it.”

CIRM is already working towards a similar goal with our iPSC Initiative.

Unlocking the secrets of leukemia stem cells

the-walking-dead-season-6-zombies

Zombies: courtesy “The Walking Dead”

Any article that has an opening sentence that says “Cancer stem cells are like zombies” has to be worth reading. And a report in ScienceMag  that explains how pre-leukemia white blood cell precursors become leukemia cancer stem cells is definitely worth reading.

The article is about a study in the journal Cell Stem Cell by researchers at UC San Diego. The senior author is Catriona Jamieson:

“In this study, we showed that cancer stem cells co-opt an RNA editing system to clone themselves. What’s more, we found a method to dial it down.”

An enzyme called ADAR1 is known to spur cancer growth by manipulating small pieces of genetic material known as microRNA. Jamieson and her team wanted to track how that was done. They discovered it is a cascade of events, and that once the first step is taken a series of others quickly followed on.

They found that when white blood cells have a genetic mutation that is linked to leukemia, they are prone to inflammation. That inflammation then activates ADAR1, which in turn slows down a segment of microRNA called let-7 resulting in increased cell growth. The end result is that the white blood cells that began this cascade become leukemia stem cells and spread an aggressive and frequently treatment-resistant form of the blood cancer.

Having uncovered how ADAR1 works Jamieson and her team then tried to find a way to stop it. They discovered that by blocking the white blood cells susceptibility to inflammation, they could prevent the cascade from even starting. They also found that by using a compound called 8-Aza they could impede ADAR1’s ability to stimulate cell growth by around 40 percent.

Jamieson

Catriona Jamieson – definitely not a zombie

Jamieson says the findings open up all sorts of possibilities:

“Based on this research, we believe that detecting ADAR1 activity will be important for predicting cancer progression. In addition, inhibiting this enzyme represents a unique therapeutic vulnerability in cancer stem cells with active inflammatory signaling that may respond to pharmacologic inhibitors of inflammation sensitivity or selective ADAR1 inhibitors that are currently being developed.”

This wasn’t a CIRM-funded study but we have supported other projects by Dr. Jamieson that have led to clinical trials.

 

 

 

 

Calling for a cure for HIV/AIDS

/ Kevin McCormack / Leave a comment

Larry Kramer - Photo by David Shankbone

Larry Kramer – Photo by David Shankbone

Larry Kramer is a pivotal figure in the history of HIV/AIDS. His activism on many fronts has been widely credited with changing public health policy and speeding up access to experimental medications for people infected with the virus. So when he says that the fight for treatment is not enough but “The battle cry now must be one word — cure, cure, cure!” People pay attention.

A few years ago it might have been considered dangerously optimistic to use the word “cure” in any conversation about HIV/AIDS, but that’s no longer the case. In fact cure is something that is becoming not just a wildly ambitious dream, but something that scientists are working hard to achieve right now.

On Tuesday, October 6th, we are going to hold an HIV/AIDS Cure Town Hall meeting in Palm Springs. This will be the third event we’ve held and the previous two, in San Francisco and Los Angeles, were hugely successful. It’s not hard to understand why. Our experts are going to be talking about their work in trying to eradicate the AIDS virus from people infected with it.

This includes clinical trials run by Calimmune and City of Hope/Sangamo, plus some truly cutting edge research by Dr. Paula Cannon of the University of Southern California.

The clinical trials are both taking similar, if slightly different, approaches to reach the same goal; functionally curing people with HIV. They take the patient’s own blood stem cells and genetically modify them so that the AIDS virus is no longer able to infect them. They also help boost the patient’s T cells, a key part of a healthy immune system and the virus’ main target, so that they can fight back against the virus. It’s a kind of one-two punch to block and eventually evict the virus.

Timothy Brown; photo courtesy CureAIDSreport.org

Timothy Brown; photo courtesy CureAIDSreport.org

This work is based on the real-life experiences of Timothy Ray Brown, the “Berlin Patient”. He became the first person ever cured of HIV/AIDS when he got a bone marrow transplant from a person with a natural resistance to HIV. This created a new blood supply and a new immune system both of which were resistant to HIV.

Timothy is going to be joining us at the event in Palm Springs to share his story and show that cure is not just a word it’s a goal; one that we can now think of as being possible.

The HIV/AIDS Cure Town Hall event will be held on Tuesday, October 6th in the Sinatra Auditorium at the Desert Regional Medical Center in Palm Springs. Doors open at 6pm and the program starts at 6.30pm. And of course, it’s free.