According to organ donation statistics from the Health Resources & Services Administration, over 113,000 men, women, and children are on the national transplant waiting list as of July 2019. Another person is added to the waiting list every 10 minutes and 20 people die each day waiting for a transplant.
As these statistics highlight, there is a tremendous need for obtaining viable organs for people that are in need of a transplant. It is because of this, that scientists and researchers are exploring ways of using stem cells to potentially grow fully functional organs.
In a CIRM-supported study, Dr. Hiromitsu Nakauchi at Stanford University, in collaboration with Dr. Wellington Cardoso at Columbia University, were able to grow fully functional lungs in mouse embryos using transplanted stem cells. The full study, published in Nature Medicine, suggests that it may be possible to grow human lungs in animals and use them for patients in dire need of transplants or to study new lung treatments.
In the study, the researchers took stem cells and implanted them into modified mouse embryos that either lacked the stem cells necessary to form a lung or were not able to produce enough cells to make a lung. It was found that the implanted stem cells formed fully functional lungs that allowed the mice to live well into adulthood. Additionally, there were no signs of the mouse’s body rejecting the lung tissue composed of donor stem cells.
In a press release, Dr. Cardoso expressed optimism for the study and the potential the results hold:
“Millions of people worldwide who suffer from incurable lung diseases die without treatment due to the limited supply of donor lungs for transplantation. Our study shows that it may eventually be possible to develop new strategies for generating human lungs in animals for transplantation as an alternative to waiting for donor lungs.”
At 18 years old, there are several life-changing moments that young people look forward to. For some, it involves graduating from high school, starting college, and being able to cast a vote in an election. For others, this momentous occasion symbolizes the official start of adulthood.
For James O’ Brien, this milestone was marked by a rather unfortunate event where ammonia was thrown at his face in a random attack. As a result of this incident, the surface of his right eye was burned and he was left completely blind in his right eye.
Fast forward 25 years and thanks to an experimental stem cell treatment, James is able to see out of his right eye for the first time since the attack.
“Being able to see with both eyes – it’s a small thing that means the world. Basically I went from near-blindness in that eye to being able to see everything.” said O’Brien in a news release from Daily Heralds.
Dr. Sajjad Ahmad and a team of surgeons at the Moorfields Eye Hospital in London removed healthy stem cells from O’Brien’s left eye and grew these cells in a lab for months. After an adequate number of healthy stem cells from O’Briens left eye were grown, the surgeons then cut the scar tissue in his right eye and replaced it with the healthy stem cells.
They then waited a year after the procedure for the cells to settle down before inserting a cornea – which plays a key role in vision and focuses light – from a deceased donor.
“This is going to have a huge impact. A lot of these patients are young men so it affects their work, their lives, those around them. It’s not just the vision that drops, it’s the pain.” said Dr. Ahmad in the news release previously mentioned.
The procedure used took over 20 years to develop and Dr. Ahmad hopes to continue to develop the procedure for patients that have been blinded in both eyes by chemicals or have lost their vision through degenerative conditions.
CIRM has funded three clinical trials in vision loss to date. Two of these trials are being conducted by Dr. Henry Klassen for an eye condition known as retinitis pigmentosa and have shown promising results. The third trial is being conducted by Dr. Mark Humayun for another eye condition known as age-related macular degeneration (AMD) which has also shown promising results.
See video below for a news segment of James O’Brien on BBC News:
It’s always gratifying to see research you have helped support go from being an intriguing idea to something with promise to a product that is now the focus of a company. It’s all the more gratifying if the product in question might one day help millions of people battling diabetes.
That’s the case with
a small pouch being developed by a company called Encellin. The pouch is the
brainchild of Tejal Desai, Ph.D., a
professor of bioengineering at UCSF and a CIRM grantee.
“It’s a cell encapsulation device, so this material can essentially protect beta cells from the immune system while allowing them to function by secreting insulin. We are placing stem cell-derived beta cells into the pouch which is then implanted under the skin. The cells are then able to respond to changes in sugar or glucose levels in the blood by pumping out insulin. By placing the device in a place that is accessible we can easily remove it if we have to, but also we can recharge it and put in new cells as well.”
While the pouch was developed in Dr. Desai’s lab, the idea
to take it from a promising item and try to turn it into a real-world therapy
came from one of Dr. Desai’s former students, Crystal Nyitray, Ph.D.
After getting her PhD, Nyitray went to work for the pharmaceutical giant Sanofi. In an article in FierceBiotech she says that’s where she realized that the pouch she had been working on at UCSF had real potential.
“During that time, I started to realize
we really had something, that everything that pharma or biotech was looking at
was something we had been developing from the ground up with those specific
questions in mind,”
So Dr. Nyitray went to work for QB3, the institute created
by UC San Francisco to help startups develop their ideas and get funding. The
experience she gained there gave her the confidence to be the co-founder and
CEO of Encellin.
Dr. Desai is a scientific advisor to Encellin. She says
trying to create a device that contains insulin-secreting cells is not new.
Many previous attempts failed because once the device was placed in the body,
the immune system responded by creating fibrosis or scarring around it which
blocked the ability of the cells to get out.
But she thinks their approach has an advantage over previous
“This is not a new idea, the idea has been around for 40 or
more years but getting it to work is hard. We have a convergence of getting the
right cell types and combining that with our knowledge of immunology and then
the material science where we can design materials at this scale to get the kind
of function that we need.
Dr. Nyitray ““If we can reduce fibrosis, it really
helps the cells get nutrients better, survive better and signal more
effectively. It’s really critical to their success.”
Dr. Desai says the device is still in the early stages of
being tested, but already it’s showing promise.
“We have done testing in animals. Where the company is
taking this is now to see if we can take this to larger animals and then
She says without CIRM’s support none of this would have
“CIRM has been really instrumental in helping us refine the
cell technology piece of it, to get really robust cells and also to support the
development to push the materials, to understand the biology, to really
understand what was happening with the cell material interface. We know we have
a lot of challenges ahead, but we are really excited to see if this could
We are excited too. We are looking forward to seeing what
Encellin does in the coming years. It could change the lives of millions of
people around the world.
For several years, researchers have been able to take stem cells and use them to make three dimensional structures called organoids. These are a kind of mini organ that scientists can then use to study what happens in the real thing. For example, creating kidney organoids to see how kidney disease develops in patients.
Scientists can do the same with brain cells, creating clumps
of cells that become a kind of miniature version of parts of the brain. These
organoids can’t do any of the complex things our brains do – such as thinking –
but they do serve as useful physical models for us to use in trying to develop
a deeper understanding of the brain.
Now Alysson Muotri and his team at UC San Diego – in
a study supported by two
grants from CIRM – have taken the science one step further, developing
brain organoids that allow us to measure the level of electrical activity they
generate, and then compare it to the electrical activity seen in the developing
brain of a fetus. That last sentence might cause some people to say “What?”, but
this is actually really cool science that could help us gain a deeper
understanding of how brains develop and come up with new ways to treat problems
in the brain caused by faulty circuitry, such as autism or schizophrenia.
The team developed new, more effective methods of growing
clusters of the different kinds of cells found in the brain. They then placed
them on a multi-electrode array, a kind of muffin tray that could measure
electrical impulses. As they fed the cells and increased the number of cells in
the trays they were able to measure changes in the electrical impulses they
gave off. The cells went from producing 3,000 spikes a minute to 300,000 spikes
a minute. This is the first time this level of activity has been achieved in a
cell-based laboratory model. But that’s not all.
When they further analyzed the activity of the organoids, they found there were some similarities to the activity seen in the brains of premature babies. For instance, both produced short bursts of activity, followed by a period of inactivity.
In a news
release Muotri says they were surprised by the finding:
“We couldn’t believe it at first — we
thought our electrodes were malfunctioning. Because the data were so striking,
I think many people were kind of skeptical about it, and understandably so.”
Muotri knows that this research –
published in the journal Cell Stem Cell – raises ethical issues and he is
quick to say that these organoids are nothing like a baby’s brain, that they differ
in several critical ways. The organoids are tiny, not just in size but also in
the numbers of cells involved. They also don’t have blood vessels to keep them
alive or help them grow and they don’t have any ability to think.
“They are far from being functionally
equivalent to a full cortex, even in a baby. In fact, we don’t yet have a way
to even measure consciousness or sentience.”
What these organoids do have is the ability to help us look
at the structure and activity of the brain in ways we never could before. In
the past researchers depended on mice or other animals to test new ideas or
therapies for human diseases or disorders. Because our brains are so different
than animal brains those approaches have had limited results. Just think about
how many treatments for Alzheimer’s looked promising in animal models but
failed completely in people.
These new organoids allow us to explore how new therapies
might work in the human brain, and hopefully increase our ability to develop
more effective treatments for conditions as varied as epilepsy and autism.
When Californians voted for Proposition 71 in 2004, they were investing in hope… the hope that unraveling the mysteries of stem cells could lead to new types of treatments and perhaps one day, even cures for some of the most devastating illnesses and injuries known to mankind. Making this hope a reality, however, requires much more than scientific discovery, it requires a dedicated and skilled work force that can recognize and tackle the challenges that come with such an ambitious dream.
To jump start the nascent stem cell/regenerative medicine community in California, CIRM began offering Training Grants to major research and medical institutions to attract talented PhD students and postdoctoral fellows into the field. A few years later, a second type of training program was born to attract a different, yet equally important cadre of professionals – the undergraduate, Bachelors and Master’s level scientists who are the bread and butter of any successful research endeavor.
Over the past 10 years, CIRM has supported 16 of these programs, which have proven to be among the most popular and successful CIRM initiatives to date. As of 2019, the Bridges programs have trained well over 1400 scientists, about half of whom are working full time in research positions at biotechnology companies or academic laboratories, and another third of whom are currently enrolled in a graduate or professional school.
Today, there are 14 active Bridges Programs around the state, each with unique attributes, but all sharing the core elements of stem cell-based coursework, hands-on-training through internships at world-class laboratories or biotechnology companies, and formal activities involving patient engagement and community outreach. Every year, the programs produce up to 140 well-rounded, highly skilled individuals that are ready to hit the ground running.
the most recent cohort of Bridges trainees gather for an Annual Conference to
share their research outcomes, network with their peers, and learn more about
the current opportunities and challenges facing the regenerative medicine
This year, the 10th Annual Bridges Conference was held in San Mateo, CA and included inspiring talks from scientists performing cutting edge research and running some of the first FDA-approved stem-cell based clinical trials in the state.
Perhaps the biggest highlights were hearing the real-life stories of brave individuals like Anna Simos, whose experience with life-threatening complications from diabetes inspired her life’s work of providing hope and education to those facing similar challenges.
Equally moving was the testimonial of Byron Jenkins, a multiple myeloma patient who received an experimental new CAR-T therapy in a CIRM-supported clinical trial sponsored by Poseida Therapeutics.
Last but not least, little Ronnie Kashyup, recently cured of Bubble Baby Disease through another CIRM-funded clinical trial, charmed all attendees with his larger-than-life personality while his father, Pawash Priyank, shared the story of Ronnie’s diagnosis and treatment.
In the video segments to follow:
CIRM Bridges student Sneha Santosh at San Jose State University discusses the role CIRM plays in bridging together the patient advocates with the groundbreaking research conducted by scientists.
Samori Dobson and Esther Nair, CIRM Bridges students at California State University, San Marcos, briefly discuss the positive impact that the program has had on their lives.
Below are some pictures form the 10th Annual Bridges Conference in San Mateo, CA.
For more information about CIRM Bridges Programs, see the following link and video below:
One of the favorite
events of the year for the team here at CIRM is our annual SPARK (Summer Program to Accelerate
Regenerative Medicine Knowledge) conference.
This is where high school students, who spent the summer interning at world
class stem cell research facilities around California, get to show what they
learned. It’s always an engaging, enlightening, and even rather humbling
The students, many
of whom are first generation Californians, start out knowing next to nothing
about stem cells and end up talking as if they were getting ready for a PhD.
Most say they went to their labs nervous about what lay ahead and half
expecting to do menial tasks such as rinsing out beakers. Instead they were
given a lab coat, safety glasses, stem cells and a specific project to work on.
They learned how to handle complicated machinery and do complex scientific
But most importantly
they learned that science is fun, fascinating, frustrating sometimes, but also
fulfilling. And they learned that this could be a future career for them.
We asked all the
students to blog about their experiences and the results were extraordinary.
All talked about their experiences in the lab, but some went beyond and tied their
internship to their own lives, their past and their hopes for the future.
Judging the blogs
was a tough assignment, deciding who is the best of a great bunch wasn’t easy.
But in the end, we picked three students who we thought captured the essence of
the SPARK program. This week we’ll run all those blogs.
We begin with our
third place blog by Dayita Biswas from UC Davis.
Personal Renaissance: A Journey from
Scientific Curiosity to Confirmed Passions
As I poured over the pages of my
battered Campbell textbook, the veritable bible for any biology student, I saw
unbelievable numbers like how the human body is comprised of over 30 trillion
cells! Or how we have over 220 different types of cells— contrary to my mental picture of
a cell as a circle. Science, and biology in particular, has no shortage of these
seemingly impossible Fermi-esque statistics that make one do a
My experience in science had always been studying from numerous textbooks in preparation for a test or competitions, but textbooks only teach so much. The countless hours I spent reading actually demotivated me and I constantly asked myself what was the point of learning about this cycle or that process — the overwhelming “so what?” question. Those intriguing numbers that piqued my interest were quickly buried under a load of other information that made science a static stream of words across a page.
That all changed this summer when I
had the incredible opportunity to work in the Nolta lab under my mentor,
Whitney Cary. This internship made science so much more tangible and fun to be
a part of. It was such an amazing
environment, being in the same space with people who all have the same goals
and passion for science that many high school students are not able to truly
experience. Everyone was so willing to explain what they were doing, and even
went out of their way to help if I needed papers or had dumb questions.
This summer, my project was to create embryoid bodies and characterize induced pluripotent stem cells (iPSCs) from children who had Jordan’s Syndrome, an extremely rare neurodevelopmental disease whose research has applications in Alzheimer’s and autism.
I had many highs and lows during this research
experience. My highs were seeing that my iPSCs were happy and healthy. I
enjoyed learning lab techniques like micro-pipetting, working in a biological
safety hood, feeding, freezing, and passaging cells. My lows were having to
bleach my beloved iPSCs days after they failed to survive, and having
unsuccessful protocols. However, while my project consistently failed, these
failures taught me more than my successes.
I learned that there is a large gap
between being able to read about techniques and being “book smart” and actually
being able to think critically about science and perform research. Science,
true science, is more than words on a page or fun facts to spout at a party.
Science is never a straight or easy answer, but the mystery and difficulty is
part of the reason it is so interesting. Long story short: research is hard and
it takes time and patience, it involves coming in on weekends to feed cells,
and staying up late at night reading papers.
The most lasting impact that this
summer research experience had was that everything we learn in school and the
lab are all moving us towards the goal of helping real people. This internship
renewed my passion for biology and cemented my dream of working in this field.
It showed me that I don’t have to wait to be a part of dynamic science and that
I can be a small part of something that will change, benefit, and save lives.
This internship meant being a part of something bigger than myself, something meaningful. We must always think critically about what consequences our actions will have because what we do as scientists and researchers— and human beings will affect the lives of real people. And that is the most important lesson anyone can hope to learn.
And here’s a bonus, a video put together by the SPARK students at Cedars-Sinai Medical Center.
In addition to approving funding for breast cancer related brain metastases last week, the CIRM Board also approved an additional $19.7 million geared towards our translational research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.
Before getting into the details of each project, here is a table with a brief synopsis of the awards:
TRAN1 – 11532
$3.73 million was awarded to Dr. Mark Humayun at USC to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD).
AMD is an eye disease that causes severe vision impairment, resulting in the inability to read, drive, recognize faces, and blindness if left untreated. It is the leading cause of vision loss in the U.S. and currently affects over 2 million Americans. By the year 2050, it is projected that the number of affected individuals will more than double to over 5 million. A layer of cells in the back of the eye called the retinal pigment epithelium (RPE) provide support to photoreceptors (PRs), specialized cells that play an important role in our ability to process images. The dysfunction and/or loss of RPE cells plays a critical role in the loss of PRs and hence the vision problems observed in AMD. One form of AMD is known as dry AMD (dAMD) and accounts for about 90% of all AMD cases.
The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dAMD, supporting the survival of photoreceptors in the affected retina.
TRAN1 – 11579
$6.23 million was awarded to Dr. Mark Tuszynski at UCSD to develop a neural stem cell therapy for spinal cord injury (SCI).
According to data from the National Spinal
Cord Injury Statistical Center, as of 2018, SCI affects an estimated 288,000
people in the United States alone, with about 17,700 new cases each year. There
are currently no effective therapies for SCI. Many people suffer SCI in early
adulthood, leading to life-long disability and suffering, extensive treatment
needs and extremely high lifetime costs of health care.
The approach that Dr. Tuszynski is developing will use hESCs to create neural stem cells (NSCs). These newly created NSCs would then be grafted at the site of injury of those with SCI. In preclinical studies, the NSCs have been shown to support the formation of neuronal relays at the site of SCI. The neuronal relays allow the sensory neurons in the brain to communicate with the motor neurons in the spinal cord to re-establish muscle control and movement.
TRAN1 – 11548
$4.83 million was awarded to Dr. Brian Cummings at UC Irvine to develop a neural stem cell therapy for traumatic brain injury (TBI).
TBI is caused by a bump, blow, or jolt to the head that disrupts the normal function of the brain, resulting in emotional, mental, movement, and memory problems. There are 1.7 million people in the United States experiencing a TBI that leads to hospitalization each year. Since there are no effective treatments, TBI is one of the most critical unmet medical needs based on the total number of those affected and on a cost basis.
The approach that Dr. Cummings is developing will also use hESCs to create NSCs. These newly created NSCs would be integrated with injured tissue in patients and have the ability to turn into the three main cell types in the brain; neurons, astrocytes, and oligodendrocytes. This would allow for TBI patients to potentially see improvements in issues related to memory, movement, and anxiety, increasing independence and lessening patient care needs.
TRAN1 – 11628
$4.96 million was awarded to Dr. Evan Snyder at Sanford Burnham Prebys to develop a neural stem cell therapy for perinatal hypoxic-ischemic brain injury (HII).
HII occurs when there is a lack of oxygen flow to the brain. A newborn infant’s body can compensate for brief periods of depleted oxygen, but if this lasts too long, brain tissue is destroyed, which can cause many issues such as developmental delay and motor impairment. Current treatment for this condition is whole-body hypothermia (HT), which consists of significantly reducing body temperature to interrupt brain injury. However, this is not very effective in severe cases of HII.
The approach that Dr. Snyder is developing will use an established neural stem cell (NSC) line. These NSCs would be injected and potentially used alongside HT treatment to increase protection from brain injury.
Heart disease continues to be the number one cause of death in the United States. An estimated 375,000 people have a genetic form of heart disease known as familial dilated cardiomyopathy. This occurs when the heart muscle becomes weakened in one chamber in the heart, causing the open area of the chamber to become enlarged or dilated. As a result of this, the heart can no longer beat regularly, causing shortness of breath, chest pain and, in severe cases, sudden and deadly cardiac arrest.
A CIRM funded study by a team of researchers at Stanford University looked further into this form of genetic heart disease by taking a patient’s skin cells and converting them into stem cells known as induced pluripotent stem cells (iPSCs), which can become any type of cell in the body. These iPSCs were then converted into heart muscle cells that pulse just as they do in the body. These newly made heart muscle cells beat irregularly, similar to what is observed in the genetic heart condition.
Upon further analysis, the researchers linked a receptor called PGDF to cause various genes to be more highly activated in the mutated heart cells compared to normal ones. Two drugs, crenolanib and sunitinib, interfere with the PGDF receptor. After treating the abnormal heart cells, they began beating more regularly, and their gene-activation patterns more closely matched those of cells from healthy donors.
These two drugs are already FDA-approved for treating various cancers, but previous work shows that the drugs may damage the heart at high doses. The next step would be determining the right dose of the drug. The current study is part of a broader effort by the researchers to use these patient-derived cells-in-a-dish to screen for and discover new drugs.
Dr. Joseph Wu, co-senior author of this study, and his team have generated heart muscle cells from over 1,000 patients, including those of Dr. Wu, his son, and his daughter. In addition to using skin cells, the same technique to create heart cells from patients can also be done with 10 milliliters of blood — roughly two teaspoons.
“With 10 milliliters of blood, we can make clinically usable amounts of your beating heart cells in a dish…Our postdocs have taken my blood and differentiated my pluripotent stem cells into my brain cells, heart cells and liver cells. I’m asking them to test some of the medications that I might need to take in the future.”
For years we have talked about the “promise” and the “potential” of stem cells to cure patients. But more and more we are seeing firsthand how stem cells can change a patient’s life, even saving it in some cases. That’s the theme of the 4th Annual CIRM Alpha Stem Cell Clinics Network Symposium.
It’s not your usual
symposium because this brings together all
the key players in the field – the scientists who do the research, the nurses
and doctors who deliver the therapies, and the patients who get or need those
therapies. And, of course, we’ll be there; because without CIRM’s funding to
support that research and therapies none of this happens.
We are going to look
at some of the exciting progress being made, and what is on the horizon. But
along the way we’ll also tackle many of the questions that people pose to us
every day. Questions such as:
How can you distinguish between a good
clinical trial offering legitimate treatments vs a stem cell clinic offering sham
What about the Right to Try, can’t I just
demand I get access to stem cell therapies?
How do I sign up for a clinical trial, and how
much will it cost me?
What is the experience of patients that have
participated in a stem cell clinical trial?
researchers will also talk about the real possibility of curing diseases like
sickle cell disease on a national scale, which affect around 100,000 Americans,
mostly African Americans and Hispanics. They’ll discuss the use of gene editing
to battle hereditary diseases like Huntington’s. And they’ll highlight how they
can engineer a patient’s own immune system cells to battle deadly cancers.
So, join us for what
promises to be a fascinating day. It’s the cutting edge of science. And it’s
At CIRM we are always happy to highlight success stories, particularly when they involve research we are funding. But we are also mindful of the need not to overstate a finding. To quote the Greek philosopher Aristotle (who doesn’t often make an appearance on this blog), “one swallow does not a summer make”. In other words, one good result doesn’t mean you have proven something works. But it might mean that you are on the right track. And that’s why we are welcoming the news about a clinical trial we are funding with Sangamo Therapeutics.
The trial is for the treatment of beta-thalassemia, (beta-thal) a severe form of anemia caused by a genetic mutation. People with beta-thal require life-long blood transfusions because they have low levels of hemoglobin, a protein needed to help the blood carry oxygen around the body. Those low levels of oxygen can cause anemia, fatigue, weakness and, in severe cases, can lead to organ damage and even death. The life expectancy for people with the more severe forms of the condition is only 30-50 years.
In this clinical
trial the Sangamo team takes
a patient’s own blood stem cells and, using a gene-editing technology called
zinc finger nuclease (ZFN), inserts a working copy of the defective hemoglobin
gene. These modified cells are given back to the patient, hopefully generating
a new, healthy, blood supply which potentially will eliminate the need for
chronic blood transfusions.
announced that the first patient treated in this clinical trial seems to be
doing rather well.
The therapy, called
ST-400, was given to a patient who has the most severe form of beta-thal. In
the two years before this treatment the patient was getting a blood transfusion
every other week. While the treatment initially caused an allergic reaction,
the patient quickly rebounded and in the seven weeks afterwards:
Demonstrated evidence of being able to
produce new blood cells including platelets and white blood cells
Showed that the genetic edits made by
ST-400 were found in new blood cells
Hemoglobin levels – the amount of
oxygen carried in the blood – improved.
In the first few weeks
after the therapy the patient needed some blood transfusions but in the next
five weeks didn’t need any.
Obviously, this is
encouraging. But it’s also just one patient. We don’t yet know if this will
continue to help this individual let alone help any others. A point Dr. Angela
Smith, one of the lead researchers on the project, made in a news
“While these data are very early
and will require confirmation in additional patients as well as longer
follow-up to draw any clinical conclusion, they are promising. The detection of
indels in peripheral blood with increasing fetal hemoglobin at seven weeks is
suggestive of successful gene editing in this transfusion-dependent beta
thalassemia patient. These initial results are especially encouraging given the
patient’s β0/ β0 genotype, a patient population
which has proved to be difficult-to-treat and where there is high unmet medical
a first step. But a promising one. And that’s always a great way to start.