A shot in the arm for people with bad knees


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.


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.”

Stem Cell Roundup: Improving muscle function in muscular dystrophy; Building a better brain; Boosting efficiency in making iPSC’s

Here are the stem cell stories that caught our eye this week.

Photos of the week

TGIF! We’re so excited that the weekend is here that we are sharing not one but TWO amazing stem cell photos of the week.

RMI IntestinalChip

Image caption: Cells of a human intestinal lining, after being placed in an Intestine-Chip, form intestinal folds as they do in the human body. (Photo credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute)

Photo #1 is borrowed from a blog we wrote earlier this week about a new stem cell-based path to personalized medicine. Scientists at Cedars-Sinai are collaborating with a company called Emulate to create intestines-on-a-chip using human stem cells. Their goal is to create 3D-organoids that represent the human gut, grow them on chips, and use these gut-chips to screen for precision medicines that could help patients with intestinal diseases. You can read more about this gut-tastic research here.

Young mouse heart 800x533

Image caption: UCLA scientists used four different fluorescent-colored proteins to determine the origin of cardiomyocytes in mice. (Image credit: UCLA Broad Stem Cell Research Center/Nature Communications)

Photo #2 is another beautiful fluorescent image, this time of a cross-section of a mouse heart. CIRM-funded scientists from UCLA Broad Stem Cell Research Center are tracking the fate of stem cells in the developing mouse heart in hopes of finding new insights that could lead to stem cell-based therapies for heart attack victims. Their research was published this week in the journal Nature Communications and you can read more about it in a UCLA news release.

Stem cell injection improves muscle function in muscular dystrophy mice

Another study by CIRM-funded Cedars-Sinai scientists came out this week in Stem Cell Reports. They discovered that they could improve muscle function in mice with muscular dystrophy by injecting cardiac progenitor cells into their hearts. The injected cells not only improved heart function in these mice, but also improved muscle function throughout their bodies. The effects were due to the release of microscopic vesicles called exosomes by the injected cells. These cells are currently being used in a CIRM-funded clinical trial by Capricor therapeutics for patients with Duchenne muscular dystrophy.

How to build a better brain (blob)

For years stem cell researchers have been looking for ways to create “mini brains”, to better understand how our own brains work and develop new ways to repair damage. So far, the best they have done is to create blobs, clusters of cells that resemble some parts of the brain. But now researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have come up with a new method they think can advance the field.

Their approach is explained in a fascinating article in the journal Science News, where lead researcher Bennet Novitch says finding the right method is like being a chef:

“It’s like making a cake: You have many different ways in which you can do it. There are all sorts of little tricks that people have come up with to overcome some of the common challenges.”

Brain cake. Yum.

A more efficient way to make iPS cells


Shinya Yamanaka. (Image source: Ko Sasaki, New York Times)

In 2006 Shinya Yamanaka discovered a way to take ordinary adult cells and reprogram them into embryonic-like stem cells that have the ability to turn into any other cell in the body. He called these cells induced pluripotent stem cells or iPSC’s. Since then researchers have been using these iPSC’s to try and develop new treatments for deadly diseases.

There’s been a big problem, however. Making these cells is really tricky and current methods are really inefficient. Out of a batch of, say, 1,000 cells sometimes only one or two are turned into iPSCs. Obviously, this slows down the pace of research.

Now researchers in Colorado have found a way they say dramatically improves on that. The team says it has to do with controlling the precise levels of reprogramming factors and microRNA and…. Well, you can read how they did it in a news release on Eurekalert.




Stanford Scientist Sergiu Pasca Receives Prestigious Vilcek Prize for Stem Cell Research on Neuropsychiatric Disorders

Sergiu Pasca, Stanford University

Last month, we blogged about Stanford neuroscientist Sergiu Pasca and his interesting research using stem cells to model the human brain in 3D. This month we bring you an exciting update about Dr. Pasca and his work.

On February 1st, Pasca was awarded one of the 2018 Vilcek Prizes for Creative Promise in Biomedical Science. The Vilcek Foundation is a non-profit organization dedicated to raising awareness of the important contributions made by immigrants to American arts and sciences.

Pasca was born in Romania and got his medical degree there before moving to the US to pursue research at Stanford University in 2009. He is now an assistant professor of psychiatry and behavioral sciences at Stanford and has dedicated his lab’s research to understanding human brain development and neuropsychiatric disorders using 3D brain organoid cultures derived from pluripotent stem cells.

The Vilcek Foundation produced a fascinating video (below) featuring Pasca’s life journey and his current CIRM-funded research on Timothy Syndrome – a rare form of autism. In the video, Pasca describes how his lab’s insights into this rare psychiatric disorder will hopefully shed light on other neurological diseases. He shares his hope that his research will yield something that translates to the clinic.

The Vilcek Prize for Creative Promise in Biomedical Science comes with a $50,000 cash award. Pasca along with the other prize winners will be honored at a gala event in New York City in April 2018.

You can read more about Pasca’s prize winning research on the Vilcek website and in past CIRM blogs below.

Related Links:

Creating a platform to help transplanted stem cells survive after a heart attack


Developing new tools to repair damaged hearts

Repairing, even reversing, the damage caused by a heart attack is the Holy Grail of stem cell researchers. For years the Grail seemed out of reach because the cells that researchers transplanted into heart attack patients didn’t stick around long enough to do much good. Now researchers at Stanford may have found a way around that problem.

In a heart attack, a blockage cuts off the oxygen supply to muscle cells. Like any part of our body starved off oxygen the muscle cells start to die, and as they do the body responds by creating a layer of scars, effectively walling off the dead tissue from the surviving healthy tissue.  But that scar tissue makes it harder for the heart to effectively and efficiently pump blood around the body. That reduced blood flow has a big impact on a person’s ability to return to a normal life.

In the past, efforts to transplant stem cells into the heart had limited success. Researchers tried pairing the cells with factors called peptides to help boost their odds of surviving. That worked a little better but most of the peptides were also short-lived and weren’t able to make a big difference in the ability of transplanted cells to stick around long enough to help the heart heal.

Slow and steady approach

Now, in a CIRM-funded study published in the journal Nature Biomedical Engineering, a team at Stanford – led by Dr. Joseph Wu – believe they have managed to create a new way of delivering these cells, one that combines them with a slow-release delivery mechanism to increase their chances of success.

The team began by working with a subset of bone marrow cells that had been shown in previous studies to have what are called “pro-survival factors.” Then, working in mice, they identified three peptides that lived longer than other peptides. That was step one.

Step two involved creating a matrix, a kind of supporting scaffold, that would enable the researchers to link the three peptides and combine them with a delivery system they hoped would produce a slow release of pro-survival factors.

Step three was seeing if it worked. Using fluorescent markers, they were able to show, in laboratory tests, that unlinked peptides were rapidly released over two or three days. However, the linked peptides had a much slower release, lasting more than 15 days.

Out of the lab and into animals

While these petri dish experiments looked promising the big question was could this approach work in an animal model and, ultimately, in people. So, the team focused on cardiac progenitor cells (CPCs) which have shown potential to help repair damaged hearts, but which also have a low survival rate when transplanted into hearts that have experienced a heart attack.

The team delivered CPCs to the hearts of mice and found the cells without the pro-survival matrix didn’t last long – 80 percent of the cells were gone four days after they were injected, 90 percent were gone by day ten. In contrast the cells on the peptide-infused matrix were found in large numbers up to eight weeks after injection. And the cells didn’t just survive, they also engrafted and activated the heart’s own survival pathways.

Impact on heart

The team then tested to see if the treatment was helping improve heart function. They did echocardiograms and magnetic resonance imaging up to 8 weeks after the transplant surgery and found that the mice treated with the matrix combination had a statistically improved left ventricular function compared to the other mice.

Jayakumar Rajadas, one of the authors on the paper told CIRM that, because the matrix was partly made out of collagen, a substance the FDA has already approved for use in people, this could help in applying for approval to test it in people in the future:

“This paper is the first comprehensive report to demonstrate an FDA-compliant biomaterial to improve stem cell engraftment in the ischemic heart. Importantly, the biomaterial is collagen-based and can be readily tested in humans once regulatory approval is obtained.”


New Insights into Adult Neurogenesis

To be a successful scientist, you have to expect the unexpected. No biological process or disease mechanism is ever that simple when you peel off its outer layers. Overtime, results that prove a long-believed theory can be overturned by new results that suggest an alternate theory.

UCSF scientist Arturo Alvarez-Buylla is well versed with the concept of unexpected results. His lab’s research is focused on understanding adult neurogenesis – the process of creating new nerve cells (called neurons) from neural stem cells (NSCs).

For a long time, the field of adult neurogenesis has settled on the theory that brain stem cells divide asymmetrically to create two different types of cells: neurons and neural stem cells. In this way, brain stem cells populate the brain with new neurons and they also self-renew to maintain a constant stem cell supply throughout the adult animal’s life.

New Insights into Adult Neurogenesis

Last week, Alvarez-Buylla and his colleagues published new insights on adult neurogenesis in mice in the journal Cell Stem Cell. The study overturns the original theory of asymmetrical neural stem cell division and suggests that neural stem cells divide in a symmetrical fashion that could eventually deplete their stem cell population over the lifetime of the animal.

Arturo Alvarez-Buylla explained the study’s findings in an email interview with the Stem Cellar:

Arturo Alvarez-Bulla

“Our results are not what we expected. Our work shows that postnatal NSCs are not being constantly renewed by splitting them asymmetrically, with one cell remaining as a stem cell and the other as a differentiated cell. Instead, self-renewal and differentiation are decoupled and achieved by symmetric divisions.”

In brief, the study found that neural stem cells (called B1 cells) divide symmetrically in an area of the adult mouse brain called the ventricular-subventricular zone (V-SVZ). Between 70%-80% of those symmetric divisions produced neurons while only 20%-30% created new B1 stem cells. Alvarez-Buylla said that this process would result in the gradual depletion of B1 stem cells over time and seems to be carefully choreographed for the length of the lifespan of a mouse.

What does this mean?

I asked Alvarez-Buylla how his findings in mice will impact the field and whether he expects human adult neurogenesis to follow a similar process. He explained,

“The implications are quite wide, as it changes the way we think about neural stem cell retention and aging. The cells do not seem open ended with unlimited potential to be renewed, which results in a progressive decrease in NSC number and neurogenesis with time.  Understanding the mechanisms regulating proliferation of NSCs and their self-renewal also provides new insights into how the whole process of neurogenesis is choreographed over long periods by suggesting that differentiation (generation of neurons) is regulated separately from renewal.”

He further explained that mice generate new neurons in the V-SVZ brain region throughout their lifetime while humans only appear to generate new neurons during infancy in the equivalent region of the human brain called the SVZ. In humans, he said, it remains unclear where and how many neural stem cells are retained after birth.

I also asked him how these findings will impact the development of neural stem cell-based therapies for neurological or neurodegenerative diseases. Alvarez-Buylla shared interesting insights:

“Our data also indicate that upon a self-renewing division, sibling NSCs may not be equal to each other. While one NSC might stay quiescent [non-dividing] for an extended period of time, its sister cell might become activated earlier on and either undergo another round of self-renewal or differentiate. Thus, for cell-replacement therapies it will be important to understand which kind of neuron the NSC of interest can produce, and when. The use of NSCs for brain repair requires a detailed understanding of which NSC subset will be utilized for treatment and how to induce them to produce progeny. The study also suggests that factors that control NSC renewal may be separate from those that control generation of neurons.”

Scientists developing adult NSC-based therapies will definitely need to take note of Alvarez-Buylla’s findings as some NSC populations might be more successful therapeutically than others.

Neural Stem Cells in the Wild

I’ll conclude with a beautiful image that the study’s first author, Kirsten Obernier, shared with me. It’s shows the V-SVZ of the mouse brain and a neural stem cell in red making contact with a blood vessel in green and neurons in blue.

Image of the mouse brain with a neural stem cell in red. (Credit: Kirsten Obernier, UCSF)

Kirsten described the complex morphology of B1 NSCs in the mouse brain and their dynamic behavior, which Kirsten observed by taking a time lapsed video of NSCs dividing in the mouse V-SVZ. Obernier and Alvarez-Buylla hypothesize that these NSCs could be receiving signals from their surrounding environment that tell them whether to make neurons or to self-renew.

Clearly, further research is necessary to peel back the complex layers of adult neurogenesis. If NSC differentiation is regulated separately from self-renewal, their insights could shed new light on how conditions of unregulated self-renewal like brain tumors develop.

Stem Cell Roundup: New understanding of Huntington’s; how stem cells can double your DNA; and using “the Gary Oldman of cell types” to reverse aging

This week’s roundup highlights how we are constantly finding out new and exciting ways that stem cells could help change the way we treat disease.

Our Cool Stem Cell Image of the Week comes from our first story, about unlocking some of the secrets of Huntington’s disease. It comes from the Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University

Huntington's neurons

A new approach to studying and developing therapies for Huntington’s disease

Researchers at Rockefeller University report new findings that may upend the way scientists study and ultimately develop therapies for Huntington’s disease, a devastating, inherited neurodegenerative disorder that has no cure. Though mouse models of the disease are well-established, the team wanted to focus on human biology since our brains are more complex than those of mice. So, they used CRISPR gene editing technology in human embryonic stem cells to introduce the genetic mutations that cause HD.

Though symptoms typically do not appear until adulthood, the researchers were surprised to find that in their human cell-based model of HD, abnormalities in nerve cells occur at the earliest steps in brain development. These results suggest that HD therapies should focus on treatments much earlier in life.

The researchers observed another unexpected twist: cells that lack Huntingtin, the gene responsible for HD, are very similar to cells found in HD. This suggests that too little Huntingtin may be causing the disease. Up until now, the prevailing idea has been that Huntington’s symptoms are caused by the toxicity of too much mutant Huntingtin activity.

We’ll certainly be keeping an eye on how further studies using this new model affect our understanding of and therapy development for HD.

This study was published in Development and was picked by Science Daily.

How you can double your DNA


As you can imagine we get lots of questions about stem cell research here at CIRM. Last week we got an email asking if a stem cell transplant could alter your DNA? The answer is, under certain circumstances, yes it could.

A fascinating article in the Herald Review explains how this can happen. In a bone marrow transplant bad blood stem cells are killed and replaced with healthy ones from a donor. As those cells multiply, creating a new blood supply, they also carry the DNA for the donor.

But that’s not the only way that people may end up with dual DNA. And the really fascinating part of the article is how this can cause all sorts of legal and criminal problems.

One researcher’s efforts to reverse aging


Gary Oldman: Photo courtesy Variety

“Stem cells are the Gary Oldman of cell types.” As a fan of Gary Oldman (terrific as Winston Churchill in the movie “Darkest Hour”) that one line made me want to read on in a profile of Stanford University researcher Vittorio Sebastiano.

Sebastiano’s goal is, to say the least, rather ambitious. He wants to reverse aging in people. He believes that if you can induce a person’s stem cells to revert to a younger state, without changing their function, you can effectively turn back the clock.

Sebastiano says if you want to achieve big things you have to think big:

“Yes, the ambition is huge, the potential applications could be dramatic, but that doesn’t mean that we are going to become immortal in some problematic way. After all, one way or the other, we have to die. We will just understand aging in a better way, and develop better drugs, and keep people happier and healthier for a few more years.”

The profile is in the journal Nautilus.

Making beating heart cells from stem cells just got easier

Here’s a heartwarming story for the holidays. Scientists from the Salk Institute in La Jolla, California have figured out a simple, easy way to make beating heart cells from human stem cells that will aid research and therapy development for heart disease. Their study, which received funding support from CIRM, was published last week in the journal Genes & Development.

The Salk team discovered that making beating heart tissue from human stem cells is as simple as turning off a single gene called YAP. You might be wondering how the team settled on this gene and no, it doesn’t involve pulling a random gene name out of a hat.

In previous studies, the researchers found that two cell signaling pathways, Wnt and Activin, are crucial for the development of embryonic stem cells into specialized cells like cardiomyocytes (beating heart cells). This research led to the discovery of a third pathway, controlled by YAP, which sets up a road block for cell specialization and keeps stem cells in their undifferentiated state.

Only hESCs without YAP (right panel) make heart cells (green) in one step. Blue dye marks cell nuclei. (Salk Institute)

The team deleted YAP from these stem cells using CRISPR gene editing technology, and then treated the stem cells to the Activin signaling molecule. Without YAP, exposure to Activin prompted the stem cells to develop immediately into beating cardiomyocytes that you can see beating away in the Salk video below.

Dr. Kathy Jones, Salk professor and senior author on the study, explained why this discovery is important to the field in a news release:

“This discovery is really exciting because it means we can potentially create a reliable protocol for taking normal cells and moving them very efficiently from stem cells to heart cells. Researchers and commercial companies want to easily generate cardiomyocytes to study their capacity for repair in heart attacks and disease—this brings us one step closer to being able to do that.”

First author, Conchi Estarás, emphasized how their new method for making cardiomyocytes is attractive not only for its simplicity, but also for its cost-effectiveness in enabling large-scale manufacturing of these cells for treatment.

“Instead of requiring two steps to achieve specialization, removing YAP cut it to just one step. That would mean a huge savings for industry in terms of reagent materials and expense.”

Looking ahead, Jones and her team do not plan on deleting the YAP gene from stem cells because of the potential side effects cause by the loss of YAP’s other cellular functions. Instead, they will be using commercially available molecules that can temporarily inhibit the function of YAP in hopes that this less permanent action will still readily produce beating heart cells from stem cells.

Kathy Jones and Conchi Estarás. (Image courtesy of Salk Institute)

Harnessing the body’s immune system to tackle cancer

Often on the Stem Cellar we write about work that is in a clinical trial. But getting research to that stage takes years and years of dedicated work. Over the next few months, we are profiling some of the scientists we fund who are doing Discovery (early stage) and Translational (pre-clinical) research, to highlight the importance of this work in developing the treatments that could ultimately save lives. 

This second profile in the series is by Ross Okamura, Ph.D., a science officer in CIRM’s Discovery & Translation Program.

Your immune system is your body’s main protection against disease; harnessing this powerful defense system to target a given disorder is known as immunotherapy.  There are different types of immunotherapies that have been developed over the years. These include vaccines to help generate antibodies against viruses, drugs to direct immune cell function and most recently, the engineering of immune cells to fight cancer.

Understanding How Immunotherapies Work

One of the more recent immunotherapy approaches to fight cancer that has seen rapid development is equipping a subset of immune cells (T cells) with a chimeric antigen receptor (CAR). In brief, CAR T ceIls are first removed from the patient and then engineered to recognize a specific feature of the targeted cancer cells.  This direct targeting of T cells to the cancer allows for an effective anti-cancer therapy made from your own immune system.

Simplified explanation of how CAR T cell therapies fight cancer. (Memorial Sloan Kettering)

For the first time this fall, two therapeutics employing CAR T cells targeting different types of blood cancers were approved for use by the US Food and Drug Administration (FDA) based on remarkable results found during the clinical trials. Specifically, Kymriah (developed by Novartis) was approved for treatment of acute lymphoblastic leukemia and Yescarta (developed by Kite Pharma) was approved for treatment of non-Hodgkin lymphoma.

There are drawbacks to the CAR T approach, however. Revving up the immune system to attack tumors can cause dangerous side effects. When CAR T cells enter the body, they trigger the release of proteins called cytokines, which join in the attack on the tumors. But this can also create what’s referred to as a cytokine storm or cytokine release syndrome (CRS), which can lead to a range of responses, from a mild fever to multi-organ failure and death. Balancing treatments to resolve CRS after it’s detected while still maintaining the treatment’s cancer-killing abilities is a significant challenge that remains to be overcome.  A second issue is that cancer cells can evade the immune system by no longer producing the target that the CAR-T therapy was designed to recognize. When this happens, the patient subsequently experiences a cancer relapse that is no longer treatable by the same cell therapy.

Natural Killer (NK) T cells represent another type of anti-cancer immunotherapy that is also being tested in clinical trials. NK cells are part of the innate immune system responsible for defending your body against both infection and tumor formation.  NK cells target stressed cells by releasing cell-penetrating proteins that poke holes in the cells leading to induced cell death.  As an immunotherapy, NK cells have the potential to avoid both the issues of CRS and cancer cell immune evasion as they release a more limited array of cytokines and do not rely on a specific single target to recognize tumors.  NK cells instead selectively target tumor cells due to the presence of stress-induced proteins on the cancer cells. In addition, the cancer cells lack other proteins that would normally send out a “I’m a healthy cell you can ignore me” message to NK cells. Without that message, NK cells target and kill those cancer cells.

Developing new immunotherapies against cancer

Dan Kaufman, UCSD

Dr. Dan Kaufman of the University of California at San Diego is a physician-scientist whose research group developed a method to produce functional NK cells from human pluripotent stem cells (PSC).  In order to overcome a major hurdle in the use of NK cells as an anti-cancer therapeutic, Dr. Kaufman is exploring using stem cells as a limitless source to produce a scalable, standardized, off-the-shelf product that could treat thousands of patients.  CIRM is currently funding Dr. Kaufman’s work under both a Discovery Quest award and a just recently funded Translational research award in order to try to advance this candidate approach.

In the CIRM Translational award, Dr. Kaufman is looking to cure acute myelogenous leukemia (AML) which in the US has a 5-year survival rate of 27% (National Cancer Institute, 2017) and is estimated to kill over 10,000 individuals this year (American Cancer Society, 2017).  He has previously shown that his stem cell-derived NK cells can kill human cancer cells in a dish and in mouse models, and his goals are to perform preliminary safety studies and to develop a process to scale his production of NK cells to support a clinical trial in people.  Since NK cells don’t require the patient and the donor to be a genetic match to be effective, a bank of PSC-derived NK cells derived from a single donor could potentially treat thousands of patients.

Looking forward, CIRM is also providing Discovery funding to Dr. Kaufman to explore ways to improve his existing approach against leukemia as well as expand the potential of his stem cell-derived NK cell therapeutic by engineering his cells to directly target solid tumors like ovarian cancer.

The field of pluripotent stem cell-based immunotherapies is full of game-changing potential and important innovations like Dr. Kaufman’s are still in the early stages.  CIRM recognizes the importance of supporting early stage research and is currently investing $27.9 million to fund 8 active Discovery and Translation awards in the cancer immunotherapy area.

Budgeting for the future of the stem cell agency


The CIRM Board discusses the future of the Stem Cell Agency

Budgets are very rarely exciting things; but they are important. For example, it’s useful for a family to know when they go shopping exactly how much money they have so they know how much they can afford to spend. Stem cell agencies face the same constraints; you can’t spend more than you have. Last week the CIRM Board looked at what we have in the bank, and set us on a course to be able to do as many of the things we want to, with the money we have left.

First some context. Last year CIRM spent a shade over $306 million on a wide range of research from Discovery, the earliest stage, through Translational and into Clinical trials. We estimate that is going to leave us with approximately $335 million to spend in the coming years.

A couple of years ago our Board approved a 5 year Strategic Plan that laid out some pretty ambitious goals for us to achieve – such as funding 50 new clinical trials. At the time, that many clinical trials definitely felt like a stretch and we questioned if it would be possible. We’re proving that it is. In just two years we have funded 26 new clinical trials, so we are halfway to our goal, which is terrific. But it also means we are in danger of using up all our money faster than anticipated, and not having the time to meet all our goals.

Doing the math

So, for the last couple of months our Leadership Team has been crunching the numbers and looking for ways to use the money in the most effective and efficient way. Last week they presented their plan to the Board.

It boiled down to a few options.

  • Keep funding at the current rate and run out of money by 2019
  • Limit funding just to clinical trials, which would mean we could hit our 50 clinical trial goal by 2020 but would not have enough to fund Discovery and Translational level research
  • Place caps on how much we fund each clinical trial, enabling us to fund more clinical trials while having enough left over for Discovery and Translational awards

The Board went for the third option for some good reasons. The plan is consistent with the goals laid out in our Strategic Plan and it supports Discovery and Translational research, which are important elements in our drive to develop new therapies for patients.

Finding the right size cap

Here’s a look at the size of the caps on clinical trial funding. You’ll see that in the case of late stage pre-clinical work and Phase 1 clinical trials, the caps are still larger than the average amount we funded those stages last year. For Phase 2 the cap is almost the same as the average. For Phase 3 the cap is half the amount from last year, but we think at this stage Phase 3 trials should be better able to attract funding from other sources, such as industry or private investors.

cap awards

Another important reason why the Board chose option three – and here you’ll have to forgive me for being rather selfish – is that it means the Administration Budget (which pays the salaries of the CIRM team, including yours truly) will be enough to cover the cost of running this research plan until 2020.

The bottom line is that for 2018 we’ll be able to spend $130 million on clinical stage research, $30 million for Translational stage, and $10 million for Discovery. The impact the new funding caps will have on clinical stage projects is likely to be small (you can see the whole presentation and details of our plan here) but the freedom it gives us to support the broad range of our work is huge.

And here is where to go if you are interested in seeing the different funding opportunities at CIRM.

Stem Cell Stories that Caught our Eye: Mini-Brains in the Spotlight

Here are the stem cell stories that caught our eye this week.

Two research photos really caught my eye this week and they happened to be of the same thing – mini-brains. Also referred to as brain organoids, mini-brains are tiny balls of nervous tissue grown from stem cells in the lab. They allow scientists to model early brain development and study how disease affects brain cells. Another awesome thing about mini-brains is how cool they look under a microscope.

Mini Brains Part 1

Mini-brain grown in a culture dish. (Photo by Collin Edington and Iris Lee, MIT)

I discovered the first photo in a blog by Dr. Francis Collins, the Director of the National Institutes of Health. He was featuring one of the winning images from the 2017 Koch Institute Image Awards at MIT. The mini-brain photo was taken by researchers Collin Edington and Iris Lee and took over 12 hours to make. Talk about dedication!

Collins revealed that growing mini-brains from stem cells is just the tip of the iceberg for this MIT team. The researchers have plans to grow other types of mini-organs and eventually combine them to make a “human on a chip”. This multi-organ technology will be extremely valuable for studying complex diseases like Alzheimer’s and Parkinson’s, which affect multiple systems in the body.

Mini Brains Part 2

Mini-brain. (Photo by Robert Krencik and Jessy Van Asperen)

The second photo of mini-brains is from a study published this week in Stem Cell Reports by researchers at the Houston Methodist Research Institute. The team has developed a more efficient and effective method for growing mini-brains from stem cells. Typically, the process takes weeks to grow the organoids and months to mature those organoids to the point where they develop the specific cell types and structures found in the human brain.

The Houston team found that maturing different types of brain cells from pluripotent stem cells separately and then combining these mature cells together produced mini-brains that more accurately represented the complexity of the human brain. The trick was to add the brain’s support cells, called astrocytes, to the mini-brains. The astrocytes effectively “accelerated the connections of the surrounding neurons.”

The studies first author, Robert Krencik, explained in a news release,

“We always felt like what we were doing in the lab was not precisely modeling how the cells act within the human brain. So, for the first time, when we put these cells together systematically, they dramatically changed their morphological complexity, size and shape. They look like cells as you would see them within the human brain, so now we can study cells in the lab in a more natural environment.”

Their method also cuts down the time it takes to make mini-brains which will hugely benefit neuroscience researchers who have passed on using mini-brains in their studies because of the cost and time it takes to grow them. Krencik explained,

“Normally, growing these 3-D mini brains takes months and years to develop. We have new techniques to pre-mature the cells separately and then combine them, and we found that within a few weeks they’re able to form mature interactions with each other. So, the length of time to get to that endpoint for studies is dramatically reduced with our system.”

The team plans to use this method to make patient-specific mini-brains from induced pluripotent stem cells to gain new insights into how disease affects the brain. They also hope to translate their mini-brain system into clinical trials to help patients regenerate brain damage or repair brain function.