High school and middle school teachers use summer to develop stem cell lesson plans.

At CIRM, we have developed programs that try to capture and train budding young scientific minds starting in the upper reaches of k-12 schools, through undergrad college, graduate work and post doctoral training. So, we are thrilled when one of our partner institutions takes on that challenge with a new robust effort.

Piner High teacher Heather Benson practices micropipetting.

Piner High teacher Heather Benson practices micropipetting.

The Buck Institute for Research on Aging in Marin County conducted two programs this month to empower local school teachers to build stem cell science into their lesson plans for the coming year. Both initiatives asked the teachers to give up three days of their summer vacation. The Buck’s Julie Mangada spearheaded the initiative.

Twelve middle school teachers from Marin participated in “STEAM Engine 2015,” in which they created an outline for a curriculum unit on how cells work together and process sensory information. If they teach that outline this fall for a two-four-week period they will get $200 per class for supplies and a bonus $700 stipend in the program partnered with the Marin County Office of Education.

In addition, three high school teachers from neighboring Sonoma County attended a three-day externship to develop integrated lesson plans on the theme: “How have past discoveries built the foundation for stem cell research to cure disorders in the present.” All three teach at Piner High. One, Judy Barcelon, described what she took away from the three days:

“I became inspired to challenge my students with higher level science concepts so they can understand how aging and disease happened on a cellular level.”

The three teachers and their students will work together this fall as a team to create a timeline of technical advances while learning the function of those techniques. They will then create research proposals to foster understanding of one specific disease. The activities will culminate on the CIRM-organized international Stem Cell Awareness Day October 14 with a presentation by Buck’s Mangada as well as someone from CIRM.

The local Press Democrat ran an article about the program last week.

Countdown to a cure for HIV/AIDS: California leads the way

shutterstock_98186870Not so long ago using the words ‘HIV/AIDS’ and ‘cure’ in the same sentence would have been considered inappropriate, even reckless. Although there were many antiretroviral medications that were effective at helping control the virus, there was nothing that was even remotely close to a cure on the horizon. And those therapies that had been approved were not always readily available, even in the U.S., let alone in the hardest hit countries in Africa.

Today the picture looks quite different. Cure is no longer just a distant dream, it’s a goal. CIRM has two projects that we are funding in clinical trials – one led by Calimmune Inc. and one by City of Hope and Sangamo BioSciences – whose ultimate goal is to replicate the experience of the “Berlin patient” and effectively cure people with the virus.

And we are not alone, the National Institute for Allergy and Infectious Diseases (NIAID) supports a large portfolio of investigator-initiated grants in HIV cure research, including programs to identify where HIV hides, known as the HIV reservoir, and to determine how these hideouts are established and maintained and then to get rid of them.

With this progress in mind we are partnering with the AIDS Project Los Angeles (APLA), Being Alive and the University of Southern California (USC) to host an HIV/AIDS Town Hall event called “Countdown to a Cure: California Leads the Way.”

The goal of the event is to bring together members of the HIV community and leading researchers in the field to talk about the clinical trials that are underway now, and the other approaches that are being tried to cure AIDS.

Speakers at the Town Hall are Dr. Paula Cannon, USC; Dr. David Hardy, Calimmune; Dr. John Zaia, City of Hope; and Dr. Dale Ando, Sangamo BioSciences. The conversation will be moderated by Jeff Sheehy. Jeff is not only the CIRM Board Patient Advocate member for HIV/AIDS, he’s also a long time community activist in the fight against the virus. You can hear Jeff talk about his commitment to the cause in this video.

The event is on Thursday, July 30th from 5.30p to 8.30p and we’re providing food and refreshments. The location is Fiesta Hall, Plummer Park, 7377 Santa Monica Boulevard, West Hollywood, Los Angeles. And, of course, it’s free.

If you are interested in joining us and being part of the discussion please RSVP to: daniel@beingalivela.org or call 323-874-4322.

We look forward to seeing you there.

Stem cell stories that caught our eye: Parkinson’s in a dish, synthetic blood, tracking Huntington’s and cloning

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.

3D nerve model for Parkinson’s. The wave of successes in making more complex tissues in three dimensional lab cultures continues this week with a team in Luxembourg creating nerves from stem cells derived from Parkinson’s patients that assembled into complex connections in the lab.

Nerve cells made from skin cells. Credit: Luxembourg Centre for Systems Biomedicine (LCSB), 2015

Nerve cells made from skin cells. Credit: Luxembourg Centre for Systems Biomedicine (LCSB), 2015

The name of the journal where the group published their results, Lab on a Chip, says a lot about where the field is going. While many have grown the dopamine-producing nerves lost in Parkinson’s disease in two dimensional cultures, the new technique better replicates the disease state and does it about 10-fold cheaper because the 3D bioreactors used can be automated and use less of the reagents needed to grow the cells and to tell them to become the right nerves.

They started with skin samples from patients and reprogrammed them into iPS-type stem cells. After those cells are placed in the vessel, they are matured into 90 percent pure dopamine-nerves. At that point they are ideal for testing potential drugs for any impact on the disease. The senior researcher, Ronan Fleming, explained the benefit in a press release from the University of Luxembourg, picked up by ScienceDaily:

“In drug development, dozens of chemical substances can therefore be tested for possible therapeutic effects in a single step. Because we use far smaller amounts of substances than in conventional cell culture systems, the costs drop to about one tenth the usual.”

Synthetic blood from stem cells. Making synthetic blood, particularly for people with rare blood types for which there are few donors, has long been a goal of science. Now, the British National Health Service (NHS) says it expects to begin giving patients at least one component of lab-made blood—red cells—by 2017.

Starting with adult stem cells grown in just the right solution they hope to produce large quantities of red blood cells. Initially they plan to give only small quantities to healthy individuals with rare blood types to compare them to donor blood.

“These trials will compare manufactured cells with donated blood,” said Nick Warkins of the NHS. “The intention is not to replace blood donation but provide specialist treatment for specific patient groups.”

The story got wide pick up in the British press including in the Daily Mail and in several web portals including Rocket News.

Tracking Huntington’s spread in the brain. A CIRM-funded team at the University of California, Irvine, has developed a way to track the spread of the mutant protein responsible for progression of Huntington’s disease. They were able to accurately detect the mutant protein in cerebrospinal fluid and distinguish between people who carried the mutation but were pre-symptomatic from those that had advanced disease.

The protein appears to be released by diseased cells and migrates to other cells, seeding additional damage there. Measuring levels of the protein should allow physicians to monitor progression of the disease ahead of symptoms.

“Determining if a treatment modifies the course of a neurodegenerative disease like Huntington’s or Alzheimer’s may take years of clinical observation,” said study leader Dr. Steven Potkin. “This assay that reflects a pathological process can play a key role in more rapidly developing an effective treatment. Blocking the cell-to-cell seeding process itself may turn out to be an effective treatment strategy.”

Medical News Today wrote up the research that the team published in the journal Molecular Psychiatry.

Good overview of cloning. Writing for Medical Daily, Dana Dovey has produced a good overview of the history of cloning, and more important, the reasons why reproductive cloning of human is not likely to happen any time soon.

She describes the important role a number of variations on cloning play in scientific research, and the potential to create personalized cells for patients through a process known as therapeutic cloning. But she also describes the many problems with reproductive cloning as it is practiced in animals. It is very inefficient with dozens of eggs failing to mature and often results in animals that have flaws. She quotes Robert Lanza of Advanced Cell Technologies (now Ocata Therapeutics):

“It’s like sending your baby up in a rocket knowing there’s a 50-50 chance it’s going to blow up. It’s grossly unethical.”


New tech tool speeds up stem cell research

It’s hard to do a good job if you don’t have the right tools. Now researchers have access to a great new tool that could really help them accelerate their work, a tool its developers say “will revolutionize the way cell biologists develop” stem cell models to test in the lab.

Fluidigm's Castillo system

Fluidigm’s Callisto system

The device is called Callisto™. It was created by Fluidigm thanks to two grants from CIRM. The goal was to develop a device that would allow researchers more control and precision in the ways that they could turn stem cells into different kinds of cell. This is often a long, labor-intensive process requiring round-the-clock maintenance of the cells to get them to make the desired transformation.

Callisto changes that. The device has 32 chambers, giving researchers more control over the conditions that cells are stored in, even allowing them to create different environmental conditions for different groups of cells. All with much less human intervention.

Lila Collins, Ph.D., the CIRM Science Officer who has worked closely with Fluidigm on this project over the years, says this system has some big advantages over the past:

“Creating the optimal conditions for reprogramming, stem cell culture and stem cells has historically been a tedious and manually laborious task. This system allows a user to more efficiently test a variety of cellular stimuli at various times without having to stay tied to the bench. Once the chip is set up in the instrument, the user can go off and do other things.”

Having a machine that is faster and easier to use is not the only advantage Callisto offers, it also gives researchers the ability to systematically and simultaneously test different combinations of factors, to see which ones are most effective at changing stem cells into different kinds of cell. And once they know which combinations work best they can use Callisto to reproduce them time after time. That consistency means researchers in different parts of the world can create cells under exactly the same conditions, so that results from one study will more readily support and reflect results from another.

In a news release about Callisto,  Fluidigm’s President and CEO Gajus Worthington, says this could be tremendously useful in developing new therapies:

“Fluidigm aims to enable important research that would otherwise be impractical. The Callisto system incorporates some of our finest microfluidic technology to date, and will allow researchers to quickly and easily create complex cell culture environments. This in turn can help reveal how stems cells make fate decisions. Callisto makes challenging applications, such as cellular reprogramming and analysis, more accessible to a wide range of scientists. We believe this will move biological discovery forward significantly.”

And as Collins points out, Callisto doesn’t just do this on a bulk level, working with millions of cells at a time, the way the current methods do:

“Using a bulk method it’s possible that one might miss an important event in the mixture. The technology in this system allows the user to stimulate and study individual cells. In this way, one could measure changes in small sub-populations and find ways to increase or decrease them.”

Having the right tools doesn’t always mean you are going to succeed, but it certainly makes it a lot easier.

Using your own tumor to fight skin cancer

Some things never get old. Like watching the sunset over the Grand Canyon. Listening to a baby laugh. Watching the San Francisco Giants win the baseball World Series. Now you can add to that list learning that one of the clinical trials we are funding has just treated their first patient.

shutterstock_85468885The latest to join that growing list is Caladrius Biosciences (previously called NeoStem). We recently awarded them $17.7 million to carry out a Phase 3 metastatic melanoma clinical trial targeting cancer stem cells. These cells are believed to be able to survive chemotherapy and other cancer-targeting treatments, and can cause a relapse by enabling tumors to grow and spread.

Caladrius’ approach is a personalized one. They use the patient’s own tumor cells to create a therapeutic vaccine called (for now at least) CLBS20. It’s designed to engage the patient’s own immune system and destroy the cancer.

This first patient was treated at Thomas Jefferson University Hospital in Philadelphia. Altogether Caladrius hopes to enroll some 250 patients at more than 40 sites worldwide, for the trial. Seven of those sites are here in California; that’s the portion of the project we are funding.

Because this is a randomized, double blind study it’s not known if the patient was treated with CLBS20 or a placebo. But in a news release Dr. David J. Mazzo, CEO of Caladrius Biosciences, says it’s a big first step:

“The dosing of the first patient in this Phase 3 trial is an important milestone for our Company and the timing underscores our focus on this program and our commitment to impeccable trial execution. We are delighted by the enthusiasm and productivity of the team at Jefferson University and other trial sites around the country and look forward to translating that into optimized patient enrollment and a rapid completion of the Phase 3 trial.”

In the earlier Phase 2 trial, 72 percent of those who got the therapy were still alive after two years, compared to 31 percent of people who got a placebo therapy. There was another bonus for patients; the treatment was well-tolerated with few side effects, the most common being irritation and a reaction at the site of the injection.

There’s a big need for this approach. In 2014 there were approximately 20,000 new cases of metastatic melanoma and nearly 10,000 deaths. It usually causes death within one to two years and only 10 to 15 percent of patients survive five years.

Here’s where to go if you would like more information on the Intus Study or you can also visit the NIH clinical trials site.

Fate of our nerve stem cells determined early in embryo so the few we have as adults have very specific roles

Adult nerve stem cells fall in the category of allusive creatures. A few scientists still question their existence and most suggest they exist in small numbers only in one or two locations in the adult brain. In any case, all agree they are not particularly good at the normal function of stem cells—making repairs to their surrounding tissue.

A research team at the University of California, San Francisco, recently published results providing two reasons why adult nerve stem cells are not very robust. First they don’t self-renew—make more copies of themselves—on a regular basis.

While we have many types of nerves in our brains, our adult stem cells seem preprogrammed to form certain ones.

While we have many types of nerves in our brains, our adult stem cells seem preprogrammed to form certain ones.

Second, the ones you were born with were preprogrammed before birth to become only a narrow subset of the many nerves we need for a fully functioning brain.

Working in mice, the team led by Arturo Alvarez-Buylla found several types of stem cells on the walls of cavities in the brain and each was pre-programmed to be “progenitors” for a specific subset of nerves. Like progenitors appeared to be lumped together by location and the team also tracked the time during embryo development when these destiny designations are made.

These results could make folks reconsider how they might use adult nerve stem cells for therapy. Alvarez-Buylla explained in a UCSF press release picked up by ScienceNewsline:

“It may be unwelcome news for those who thought of adult neural stem cells as having a wide potential for neural repair. Instead, it looks as if that potential is narrowed down very early during embryonic development. It’s almost as if the embryo is planning for the future.”

He went on to argue that the study points out the critical importance of understanding how stem cells develop and change in the embryo because that knowledge will guide how we use the various stem cells in therapy.

CIRM did not fund this study, but we do fund work in the Alvarez-Buylla lab that seeks to create nerve cells that can be implanted into people with diseases like epilepsy that result from an imbalance between different types of nerves.

Help us chart a new direction

It’s hard to get where you want to go without a map. Even if you have a pretty good idea of where you are heading it’s all too easy to get sidetracked or take a wrong turn. Having a good map helps you stay on course.

Charting a course for success

Charting a course for success

That’s why we are creating our own map, to help us reach our goal, of accelerating stem cell therapies to patients with unmet medical needs.

We’re putting together a new Strategic Plan, something that will help shape our future as we head into our second decade. The idea is simple, how can we best use the money we have left (almost one billion dollars) and all our other resources.

To do that we’re asking the usual suspects for their thoughts and ideas, but we’re also asking some unusual suspects, in fact, we’re asking anyone who is interested to help us develop the plan.

As our President and CEO, Dr. C. Randal Mills, said in a news release LINK:

“No one has a monopoly on good ideas, that’s why we want to hear from a diverse group of people, scientists and non-scientists alike, to learn what they think about how we should best use our money, resources, and expertise to reach our goal. This new Strategic Plan will help create a clear vision for how we move forward, one that sets priorities and an actionable approach to accomplish our mission.”

Anyone wishing to add their voice to those helping us develop the plan can take the online anonymous survey. The deadline is the end of the day Friday, June 26th.


As the Chair of our governing Board, Jonathan Thomas, Ph.D., J.D., says:

“We are a state agency. We were created by the people of California and we answer to the people of California. It makes sense that for something this important, a Strategic Plan that will help shape our future for years to come, that we ask the people of California for their thoughts and suggestions.”

Science is filled with uncertainty. Even the most promising therapeutic approach can take a wrong turn. Having a clear road map, a well thought out Strategic Plan, is no guarantee of success, but it certainly means we’ll have a much better idea of how to get where we want to go.

Hed: Stem cell stories that caught our eye: the why’s of heart failure, harnessing stem cells’ repair kits and growing organs

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

Stem cell model sheds light on heat failure. Pretty much everyone who has heart failure due to cardiomyopathy—where the heart muscle doesn’t work as effectively as it should—or has a condition that could lead there, is taking a beta blocker. The beta-andrenergic pathway, a key molecular pathway in the heart, dysfunctions in patients with cardiomyopathy and we have never known exactly why. We just know these drugs help.

Now, a team at Stanford led by Joseph Wu has used skin samples from patients and normal subjects to create reprogrammed iPS type stem cells, grown them into heart muscle, and compared them at a very fine-tuned molecular level.

Some patients have a mutation in a protein called TNNT2 in heart muscle fibers, which regulates muscle contraction. So, one thing they looked at was the impact of that mutation. Wu’s team followed the actions triggered by this mutation and found they lead to the beta-andrenergic pathway. Wu explained the value he sees in this fundamental understanding of the disease in a Stanford press release:

“As a cardiologist, I feel this basic research study is very clinically relevant. The beta-andrenergic pathway is a major pharmaceutical target for many cardiac conditions. This study confirms that iPS-cell-derived cardiomyocytes can help us understand biologically important pathways at a molecular level, which can aid in drug screening.”

CIRM did not fund this project but we do fund other projects in Wu’s lab including one to advance the use of iPS cells as models of heart disease, one using tissue engineering to repair damaged areas of the heart and one using embryonic stem cells to generate new heart muscle.

Harnessing stem cells’ repair kits. Stem cells repair tissue in multiple ways, but primarily by maturing into cells that replace damaged ones or by excreting various chemicals that give marching orders to neighboring cells to get busy and make the repairs. Those chemicals, collectively called paracrine factors, get excreted by the stem cells in vessels known as exosomes. So, a team at Temple University in Philadelphia decided to try injecting just the exosomes, rather than whole stem cells to repair heart damage. It seemed to work pretty well in mice.

Stem cells release exosomes, tiny vessels that act as repair kits.

Stem cells release exosomes, tiny vessels that act as repair kits.

After treatment with the exosomes, mice with induced heart attacks showed fewer heart cells dying, less scar tissue, more development of new blood vessels and a stronger heart function. The head of the Temple team, Raj Kishore, described the result in a university press release distributed by EuekaAlert:

“You can robustly increase the heart’s ability to repair itself without using the stem cells themselves. Our work shows a unique way to regenerate the heart using secreted vesicles from embryonic stem cells.”

The team went on to isolate a specific regulatory chemical that was among the most abundant in the exosomes. That compound, a type of RNA, produced much of the same results when administered by itself to the mice—intriguing results for further study.

Good primer on using stem cells to grow organs. The Wisconsin State Journal ran a nice primer in both video and prose about what would theoretically go into building a replacement organ from stem cells and some of the basic stem cell principals involved. The piece is part of a series the paper produces with the Morgridge Institute at the University of Wisconsin. This one features an interview with Michael Treiman of Epic Systems:

“The biggest challenge right now is that we can push a stem cell to be a particular type of cell, but in a tissue there’s multiple cells. And an organ like your heart or brain isn’t just made of one cell type; it’s made of many cell types working together.”

Holy Guacamole! Nutrient in Avocado Kills Cancer Stem Cells

Over four billion avocados were sold last year in the U.S. and for good reason – they’re so darn delicious and good for you too (wish you could say the same for doughnuts). Often called the world’s perfect food, avocados are high in fiber and packed with vitamins. Even the fat they contain is the healthy kind that’s associated with lower cholesterol levels and healthier hearts. As if the news couldn’t get any better, research published this week now suggests that a nutrient found in avocado can kill cancer stem cells – a cell type thought to be the source of a cancer’s unlimited growth and spread.

avocado, the world's perfect food

avocado, the world’s perfect food

The study, reported in Cancer Research by a Canadian research team at the University of Waterloo, focuses on a particularly deadly form of blood cancer called acute myeloid leukemia (AML). Often striking adults over 65, AML has a poor prognosis with only 10% survival after five years for this age group.

The cancer is caused by rapid, abnormal growth of white blood cells in the bone marrow that eventually crowds out normal blood cells leading to a deterioration of vital functions of the blood like carrying oxygen to the body. Chemotherapy or bone marrow transplants are standard treatments but unfortunately, even when successful, a majority of AML patients will relapse.

Though they make up a tiny portion of the leukemia, cancer stem cells are thought to be the main culprits behind AML relapse due to their stem cell-like ability for unlimited growth. The research team identified a nutrient in avocados called avocatin B with the ability to kill AML cancer stem cells. The killing mechanism of avocatin B was pinpointed to its disruption of the mitochondria, the cell’s energy “factory”, in leukemia cells, which led to cell death. As senior author Professor Paul Spagnuolo points out in a university press release, this cancer killing property of avocatin B promises to have limited side effects:

“We’ve performed many rounds of testing to determine how this new drug works at a molecular level and confirmed that it targets [cancer] stem cells selectively, leaving healthy cells unharmed.”

Now, before you rush out to the grocery store and stock up on nothing but avocados, keep in mind this is a preliminary study in petri dishes. Extensive follow up studies will be required before testing in humans can begin. Also, it’s not clear if eating avocado or an avocado extract would be a sufficient method of delivering avocatin B to keep cancer stem cells at bay. It’s more likely that avocatin B would be purified and provided as a food nutrient drug or a so-called nutraceutical:

“Extracts are less refined. The contents of an extract can vary from plant to plant and year to year, depending on lots of factors – on the soil, the location, the amount of sunlight, the rain,” explains Spagnuolo. “Evaluating a nutraceutical as a potential clinical drug requires in-depth evaluation at the molecular level. This approach provides a clearer understanding of how the nutraceutical works, and it means we can reproduce the effects more accurately and consistently. This is critical to safely translating our lab work into a reliable drug that could be used in oncology clinics.”

I look forward to following this story in the months and years to come with the hope that families devastated by an AML diagnosis will have more treatment options.

New stem cell could unlock key to colon cancer

One of the fascinating things about stem cell research is how quickly the field is evolving. It seems like every other day a new study is published that highlights a new discovery that makes us stop and think how this new knowledge affects our understanding of stem cells and the diseases we are trying to treat.

The latest example came this week with research from Canada identifying a new kind of stem cell population found in the colon that can lead to cancer growth.

shutterstock_280962560The study, published in the journal Cell Stem Cell,  is important because colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer death in both men and women, claiming around 50,000 lives in the U.S. alone every year.

Stem cells are essential for helping replace the lining of our colon and intestine every three or four days. In the intestine there are two kinds of stem cells, a rapidly recycling one called Lgr5+ and a slower one. However, scientists had only been able to identify Lgr5+ stem cells in the colon. Because this stem cell type is sensitive to radiation physicians believed that radiation therapy would be effective against colon cancer.

Now, researchers at Lawson Health Research Institute in Ontario, Canada, have identified another stem cell in the colon, one that is both long-lived and radiation resistant.

They also found that this new stem cell population can not only give rise to tumors in the colon, it can also help sustain and support the growth of the cancer.

In a news release Dr. Samuel Asfaha, a clinician-scientist at Lawson and the lead author of the study, says this new piece of information gives them vital new information in fighting the cancer:

 “The identification of more than one stem cell pool in the colon has proven challenging. These findings are exciting, as we have identified an important new target for cancer therapy. It is also proof that more than one stem cell can give rise to and sustain tumors, telling us that our cancer therapy needs to target more than one stem cell pool.”

Asfaha says knowing that there is a pool of stem cells that don’t respond to radiation means researchers must now look for new, more effective ways of tackling them, so we are better able to help patients with colon cancer.

CIRM is funding a number of therapies that target solid tumor cancers, the kind that includes colon cancer. One, run by Dr. Dennis Slamon of University College, Los Angeles, is now in clinical trials. You can read about that work here.