Problems with blood stem cells, a type of stem cell in your bone marrow that gives rise to various kinds of blood cells, can sometimes result in blood cancer as well as genetic and autoimmune diseases.
It is because of this that researchers have looked towards blood stem cell transplants, which involves replacing a person’s defective blood stem cells with healthy ones take from either a donor or the patient themselves.
However, before this can be done, the existing population of defective stem cells must be eradicated in order to allow the transplanted blood stem cells to properly anchor themselves into the bone marrow. Current options for this include full-body radiation or chemotherapy, but these approaches are extremely toxic.
But what if there was a way to selectively target these blood stem cells in order to make the transplants much safer?
An article published in Nature highlights the advancements made in the field of blood stem cell transplantation, some of which is work that is funded by yours truly.
The article discusses how Forty Seven tested two antibodies in monkeys. One antibody blocks the activity of a molecule called c-Kit, which is found on blood stem cells. The other is the antibody that blocks CD47, which is found on some immune cells. Inhibiting CD47 allows those immune cells to sweep up the stem cells that were targeted by the c-Kit antibody, thereby boosting its effectiveness. In early tests, the two antibodies used together reduced the number of blood stem cells in bone marrow. The next step for this team is to demonstrate that the treatment clears out the old supply of stem cells well enough to allow transplanted cells to flourish.
Another notable segment of this article is the CIRM funded trial that is being conducted by Dr. Judith Shizuru at Stanford University. This clinical trial also uses an antibody that targets c-Kit found on blood stem cells.
The purpose of this trial is to wipe out the problematic blood stem cells in infants with X-linked Severe combined immunodeficiency (SCID), a rare fatal genetic disorder that leaves infants without a functional immune system, in order to introduce properly functioning blood stem cells. Dr. Shizuru and her team found that transplanted blood stem cells, in this case from donors who did not have the disease, successfully took hold in the bone marrow of four out of six of the babies.
You can read more about Dr. Shizuru’s work in a previous blog post as well.
Blood stem cells are a vital part of us. They create all the other kinds of blood cells in our body and are used in bone marrow transplants to help people battling leukemia or other blood cancers. The problem is growing these blood stem cells outside the body has always proved challenging. Up till now.
Researchers at UCLA, with CIRM funding, have identified a protein that seems to play a key role in helping blood stem cells renew themselves in the lab. Why is this important? Because being able to create a big supply of these cells could help researchers develop new approaches to treating a wide array of life-threatening diseases.
One of the most important elements that a stem cell has is its ability to self-renew itself over long periods of time. The problem with blood stem cells has been that when they are removed from the body they quickly lose their ability to self-renew and die off.
To discover why this is the case the team at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA analyzed blood stem cells to see which genes turn on and off as those cells turn into other kinds of blood cells – red, white and platelets. They identified one gene, called MLLT3, which seemed to play a key role in helping blood stem cells self-renew.
To test this finding, the researchers took blood stem cells and, in the lab, inserted copies of the MLLT3 gene into them. The modified cells were then able to self-renew at least 12 times; a number far greater than in the past.
Dr. Hanna Mikkola, a senior author of the study says this finding could help advance the field:
“If we think about the amount of blood stem cells needed to treat a patient, that’s a significant number. But we’re not just focusing on quantity; we also need to ensure that the lab-created blood stem cells can continue to function properly by making all blood cell types when transplanted.”
Happily, that seemed to be the case. When they subjected the MLLT3-enhanced blood stem cells to further analysis they found that they appeared to self-renew at a safe rate and didn’t multiply too much or mutate in ways that could lead to leukemia or other blood cancers.
The next steps are to find more efficient and effective ways of keeping the MLLT3 gene active in blood stem cells, so they can develop ways of using this finding in a clinical setting with patients.
Their findings are published in the journal Nature.
satisfying to see two projects you have supported for a long time do well. That’s
particularly true when the projects in question are targeting conditions that
have no other effective therapies.
This week we learned
that a clinical trial we funded to help people with spinal cord injuries
continues to show benefits. This trial holds a special place in our hearts
because it is an extension of the first clinical trial we ever funded.
Initially it was with Geron,
and was later taken up by Asterias
Biotherapeutics, which has seen been bought by Lineage Cell Therapeutics Inc.
The therapy involved transplanting oligodendrocyte progenitor cells (OPCs), which are derived from human embryonic stem cells, into people who suffered recent spinal cord injuries that left them paralyzed from the neck down. OPCs play an important role in supporting and protecting nerve cells in the central nervous system, the area damaged in a spinal cord injury. It’s hoped the cells will help restore some of the connections at the injury site, allowing patients to regain some movement and feeling.
In a news
release, Lineage said that its OPC
therapy continues to report positive results, “where the overall safety profile
of OPC1 has remained excellent with robust motor recovery in upper extremities
maintained through Year 2 patient follow-ups available to date.”
Two years in the
patients are all continuing to do well, and no serious unexpected side effects
have been seen. They also reported:
– Motor level improvements
Five of six Cohort 2 patients achieved
at least two motor levels of improvement over baseline on at least one side as
of their 24-month follow-up visit.
In addition, one Cohort 2 patient
achieved three motor levels of improvement on one side over baseline as of the
patient’s 24-month follow-up visit; improvement has been maintained through the
patient’s 36-month follow-up visit.
Brian M. Culley, CEO of Lineage Cell Therapeutics called the news “exciting”, saying “To put these improvements into perspective, a one motor level gain means the ability to move one’s arm, which contributes to the ability to feed and clothe oneself or lift and transfer oneself from a wheelchair. These are tremendously meaningful improvements to quality of life and independence.”
The other good news came from Orchard Therapeutics, a company we have
partnered with on a therapy for Severe Combined Immunodeficiency (SCID) also
known as “bubble baby diseases” (we have blogged about this a lot including
In a news
release Orchard announced that the European Medicines Agency (EMA) has granted an accelerated
assessment for their gene therapy for metachromatic leukodystrophy (MLD). This
is a rare and often fatal condition that results in the build-up of sulfatides
in the brain, liver, kidneys and other organs. Over time this makes it harder
and harder for the person to walk, talk, swallow or eat.
Anne Dupraz-Poiseau, chief regulatory
officer of Orchard Therapeutics, says this is testimony to the encouraging
early results of this therapy. “We look forward to working with the EMA to
ensure this potentially transformative new treatment, if approved, reaches
patients in the EU as quickly as possible, and continuing our efforts to expand
patient access outside the EU.”
The accelerated assessment potentially
provides a reduced review timeline from 210 to 150 days, meaning it could be
available to a wider group of patients sooner.
Chronic myelogenous leukemia (CML) is a cancer of the white blood cells. It causes them to increase in number, crowd out other blood cells, leading to anemia, infection or heavy bleeding. Up until the early 2000’s the main weapon against CML was chemotherapy, but the introduction of drugs called tyrosine kinase inhibitors changed that, dramatically improving long term survival rates.
However, these medications are not a
cure and do not completely eradicate the leukemia stem cells that can fuel the
growth of the cancer, so if people stop taking the medication the cancer can
But now Dr. John Chute and a team of researchers at UCLA, in a CIRM-supported study, have found a way to target those leukemia stem cells and possibly eliminate them altogether.
The team knew that mice that had the genetic mutation
responsible for around 95 percent of CML cases normally developed the disease
and died with a few months. However, mice that had the CML gene but lacked
another gene, one that produced a protein called pleiotrophin, had normal white
blood cells and lived almost twice as long. Clearly there was something about
pleiotrophin that played a key role in the growth of CML.
They tested this by transplanting blood stem cells from mice
with the CML gene into healthy mice. The previously healthy mice developed
leukemia and died. But when they did the same thing from mice that had the CML
gene but lacked the pleiotrophin gene, the mice remained healthy.
So, Chute and his team wanted to know if the same thing
happens in human cells. Studying human CML stem cells they found these had not
just 100 times more pleiotrophin than ordinary cells, they were also producing
their own pleiotrophin.
In a news release Chute, said this was unexpected:
“This provides an example of cancer stem cells
that are perpetuating their own disease growth by hijacking a protein that
normally supports the growth of the healthy blood system.”
Next Chute and the team developed an antibody that blocked
the action of pleiotrophin and when they tested it in human cells the CML stem
Then they combined this antibody with a drug called imatinib
(better known by its brand name, Gleevec) which targets the genetic abnormality
that causes most forms of CML. They tested this in mice who had been
transplanted with human CML stem cells and the cells died.
“Our results suggest that it may be possible to eradicate
CML stem cells by combining this new targeted therapy with a tyrosine kinase
inhibitor,” said Chute. “This could lead to a day down the road when people
with CML may not need to take a tyrosine kinase inhibitor for the rest of their
The next step is for the researchers to modify the antibody so that it is better suited for humans and not mice and to see if it is effective not just in cells in the laboratory, but in people.
Within all of our bodies there is a special type of “super” immune cell that holds enormous potential. Unlike regular immune cells that can only attack one cancer at a time, these “super” immune cells have the ability to target many types of cancers at once. These specialized cells are known as invariant natural killer T cells or iNKT cells for short. Unfortunately, there are relatively few of these cells normally present in the body.
However, in a CIRM-funded study, Dr. Lily Yang and her team of researchers at UCLA have found a way to produce iNKT cells from human blood stem cells. They were then able to test these iNKT cells on mice with both human bone marrow and human cancers. These mice either had multiple melanoma, a type of blood cancer, or melanoma, a solid tumor cancer. The researchers then studied what happened to mice’s immune system, cancers, and engineered iNKT cells after they had integrated into the bone marrow.
The results were remarkable. The team found that the blood stem cells now differentiated normally into iNKT cells, producing iNKT cells for the rest of the animal’s life, which was generally about a year. Mice without the engineered stem cell transplants had undetectable levels of iNKT cells while those that received the engineered cells had iNKT cells make up as much as 60% of the total immune system cells. The team also found that the engineered iNKT cells were able to suppress tumor growth in both multiple myeloma and melanoma.
Dr. Yang, in a press release by UCLA health, discussed the significance of the results in this animal model and the enormous potential this could have for cancer patients.
“What’s really exciting is that we can give this treatment just once and it increases the number of iNKT cells to levels that can fight cancer for the lifetime of the animals.” said Yang.
In the same press release, Dr. Yang continued to highlight the study’s importance by saying that,
“One advantage of this approach is that it’s a one-time cell therapy that can provide patients with a lifelong supply of iNKT cells.”
Researchers mentioned that they could control total iNKT cell make up in the immune system depending on how they engineered the blood stem cells. However, more research is needed to determine how these engineered iNKT cells might be useful for treating cancer in humans and evaluating any long-term side effects associated with an increased number of these cells.
The full results of this study were published in the journal Cell Stem Cell.
Chemotherapy and radiation are two of the front-line weapons in treating cancer. They can be effective, even life-saving, but they can also be brutal, taking a toll on the body that lasts for months. Now a team at UCLA has developed a therapy that might enable the body to bounce back faster after chemo and radiation, and even make treatments like bone marrow transplants easier on patients.
First a little
background. Some cancer treatments use chemotherapy and radiation to kill the
cancer, but they can also damage other cells, including those in the bone
marrow responsible for making blood stem cells. Those cells eventually recover
but it can take weeks or months, and during that time the patient may feel
fatigue and be more susceptible to infections and other problems.
In a CIRM-supported study, UCLA’s Dr. John Chute and his team developed a drug that speeds up the process of regenerating a new blood supply. The research is published in the journal Nature Communications.
They focused their
attention on a protein called PTP-sigma that is found in blood stem cells and
acts as a kind of brake on the regeneration of those cells. Previous studies by
Dr. Chute showed that, after undergoing radiation, mice that have less
PTP-sigma were able to regenerate their blood stem cells faster than mice that
had normal levels of the protein.
So they set out to
identify something that could help reduce levels of PTP-sigma without affecting
other cells. They first identified an organic compound with the charming name
of 6545075 (Chembridge) that was reported to be effective against PTP-sigma.
Then they searched a library of 80,000 different small molecules to find
something similar to 6545075 (and this is why science takes so long).
From that group they
developed more than 100 different drug candidates to see which, if any, were
effective against PTP-sigma. Finally, they found a promising candidate, called DJ009.
In laboratory tests DJ009 proved itself effective in blocking PTP-sigma in
human blood stem cells.
They then tested
DJ009 in mice that were given high doses of radiation. In a news
release Dr. Chute said the results were very encouraging:
“The potency of this compound in animal models was very
high. It accelerated the recovery of blood stem cells, white blood cells and
other components of the blood system necessary for survival. If found to be
safe in humans, it could lessen infections and allow people to be discharged
from the hospital earlier.”
Of the radiated mice, most that were given DJ009
survived. In comparison, those that didn’t get DJ009 died within three weeks.
They saw similar benefits in mice given chemotherapy.
Mice with DJ009 saw their white blood cells – key components of the immune
system – return to normal within two weeks. The untreated mice had dangerously
low levels of those cells at the same point.
It’s encouraging work and the team are already getting
ready for more research so they can validate their findings and hopefully take
the next step towards testing this in people in clinical trials.
There is nothing you can do to prevent or reduce your risk of leukemia. That’s not a very reassuring statement considering that this year alone almost 62,000 Americans will be diagnosed with leukemia; almost 23,000 will die from the disease. That’s why CIRM is funding four clinical trials targeting leukemia, hoping to develop new approaches to treat, and even cure it.
also why our next special Facebook Live “Ask the Stem Cell Team” event is
focused on this issue. Join us on Thursday, August 29th from
1pm to 2pm PDT to hear a discussion about the progress in, and promise of,
stem cell research for leukemia.
two great panelists joining us:
Dr. Crystal Mackall, has many titles including serving as the Founding Director of the Stanford Center for Cancer Cell Therapy. She is using an innovative approach called a Chimeric Antigen Receptor (CAR) T Cell Therapy. This works by isolating a patient’s own T cells (a type of immune cell) and then genetically engineering them to recognize a protein on the surface of cancer cells, triggering their destruction. This is now being tested in a clinical trial funded by CIRM.
Natasha Fooman. To describe Natasha as a patient advocate would not do justice to her experience and expertise in fighting blood cancer and advocating on behalf of those battling the disease. For her work she has twice been named “Woman of the Year” by the Leukemia and Lymphoma Society. In 2011 she was diagnosed with a form of lymphoma that was affecting her brain. Over the years, she would battle lymphoma three times and undergo chemotherapy, radiation and eventually a bone marrow transplant. Today she is cancer free and is a key part of a CIRM team fighting blood cancer.
We hope you’ll join
us to learn about the progress being made using stem cells to combat blood
cancers, the challenges ahead but also the promising signs that we are
advancing the field.
We also hope you’ll take an active role by posting questions on Facebook during the event, or sending us questions ahead of time to firstname.lastname@example.org. We will do our best to address as many as we can.
link to the event, feel free to share this with anyone you think might be interested
in joining us for Facebook Live “Ask the Stem Cell Team about Leukemia”
CIRM’s mission is very simple: to accelerate stem cell treatments to patients with unmet medical needs. Anne Klein’s son, Everett, was a poster boy for that statement. Born with a fatal immune disorder Everett faced a bleak future. But Anne and husband Brian were not about to give up. The following story is one Anne wrote for Parents magazine. It’s testament to the power of stem cells to save lives, but even more importantly to the power of love and the determination of a family to save their son.
My Son Was Born With ‘Bubble Boy’ Disease—But A Gene Therapy Trial Saved His Life
I wish more than anything that my son Everett had not been born with severe combined immunodeficiency (SCID). But I know he is actually one of the lucky unlucky ones. By Anne Klein
As a child in the ’80s, I watched a news story about David Vetter. David was known as “the boy in the bubble” because he was born with severe combined immunodeficiency (SCID), a rare genetic disease that leaves babies with very little or no immune system. To protect him, David lived his entire life in a plastic bubble that kept him separated from a world filled with germs and illnesses that would have taken his life—likely before his first birthday.
I was struck by David’s story. It was heartbreaking and seemed so otherworldly. What would it be like to spend your childhood in an isolation chamber with family, doctors, reporters, and the world looking in on you? I found it devastating that an experimental bone marrow transplant didn’t end up saving his life; instead it led to fatal complications. His mother, Carol Ann Demaret, touched his bare hand for the first and last time when he was 12 years old.
I couldn’t have known that almost 30 years later, my own son, Everett, would be born with SCID too.
Everett’s SCID diagnosis
At birth, Everett was big, beautiful, and looked perfectly healthy. My husband Brian and I already had a 2-and-a-half-year-old son, Alden, so we were less anxious as parents when we brought Everett home. I didn’t run errands with Alden until he was at least a month old, but Everett was out and about with us within a few days of being born. After all, we thought we knew what to expect.
But two weeks after Everett’s birth, a doctor called to discuss Everett’s newborn screening test results. I listened in disbelief as he explained that Everett’s blood sample indicated he may have an immune deficiency.
“He may need a bone marrow transplant,” the doctor told me.
I was shocked. Everett’s checkup with his pediatrician just two days earlier went swimmingly. I hung up and held on to the doctor’s assurance that there was a 40 percent chance Everett’s test result was a false positive.
After five grueling days of waiting for additional test results and answers, I received the call: Everett had virtually no immune system. He needed to be quickly admitted to UCSF Benioff Children’s Hospital in California so they could keep him isolated and prepare to give him a stem cell transplant. UCSF diagnosed him specifically with SCID-X1, the same form David battled.
Beginning SCID treatment
The hospital was 90 miles and more than two hours away from home. Our family of four had to be split into two, with me staying in the hospital primarily with Everett and Brian and Alden remaining at home, except for short visits. The sudden upheaval left Alden confused, shaken, and sad. Brian and I quickly transformed into helicopter parents, neurotically focused on every imaginable contact with germs, even the mildest of which could be life-threatening to Everett.
When he was 7 weeks old, Everett received a stem cell transplant with me as his donor, but the transplant failed because my immune cells began attacking his body. Over his short life, Everett has also spent more than six months collectively in the hospital and more than three years in semi-isolation at home. He’s endured countless biopsies, ultrasounds, CT scans, infusions, blood draws, trips to the emergency department, and medical transports via ambulance or helicopter.
Gene therapy to treat SCID
At age 2, his liver almost failed and a case of pneumonia required breathing support with sedation. That’s when a doctor came into the pediatric intensive care unit and said, “When Everett gets through this, we need to do something else for him.” He recommended a gene therapy clinical trial at the National Institutes of Health (NIH) that was finally showing success in patients over age 2 whose transplants had failed. This was the first group of SCID-X1 patients to receive gene therapy using a lentiviral vector combined with a light dose of chemotherapy.
After the complications from our son’s initial stem cell transplant, Brian and I didn’t want to do another stem cell transplant using donor cells. My donor cells were at war with his body and cells from another donor could do the same. Also, the odds of Everett having a suitable donor on the bone marrow registry were extremely small since he didn’t have one as a newborn. At the NIH, he would receive a transplant with his own, perfectly matched, gene-corrected cells. They would be right at home.
Other treatment options would likely only partially restore his immunity and require him to receive infusions of donor antibodies for life, as was the case with his first transplant. Prior gene therapy trials produced similarly incomplete results and several participants developed leukemia. The NIH trial was the first one showing promise in fully restoring immunity, without a risk of cancer. Brian and I felt it was Everett’s best option. Without hesitation, we flew across the country for his treatment. Everett received the gene therapy in September 2016 when he was 3, becoming the youngest patient NIH’s clinical trial has treated.
It’s been more than two years since Everett received gene therapy and now more than ever, he has the best hope of developing a fully functioning immune system. He just received his first vaccine to test his ability to mount a response. Now 6 years old, he’s completed kindergarten and has been to Disney World. He plays in the dirt and loves shows and movies from the ’80s (maybe some of the same ones David enjoyed).
Everett knows he has been through a lot and that his doctors “fixed his DNA,” but he’s focused largely on other things. He’s vocal when confronted with medical pain or trauma, but seems to block out the experiences shortly afterwards. It’s sad for Brian and me that Everett developed these coping skills at such a young age, but we’re so grateful he is otherwise expressive and enjoys engaging with others. Once in the middle of the night, he woke us up as he stood in the hallway, exclaiming, “I’m going back to bed, but I just want you to know that I love you with all my heart!”
I wish more than anything that Everett had not been born with such a terrible disease and I could erase all the trauma, isolation, and pain. But I know that he is actually one of the lucky unlucky ones. Everett is fortunate his disease was caught early by SCID newborn screening, which became available in California not long before his birth. Without this test, we would not have known he had SCID until he became dangerously ill. His prognosis would have been much worse, even under the care of his truly brilliant and remarkable doctors, some of whom cared for David decades earlier.
When Everett was 4, soon after the gene therapy gave him the immunity he desperately needed, our family was fortunate enough to cross paths with David’s mom, Carol Ann, at an Immune Deficiency Foundation event. Throughout my life, I had seen her in pictures and on television with David. In person, she was warm, gracious, and humble. When I introduced her to Everett and explained that he had SCID just like David, she looked at Everett with loving eyes and asked if she could touch him. As she touched Everett’s shoulder and they locked eyes, Brian and I looked on with profound gratitude.
Anne Klein is a parent, scientist, and a patient advocate for two gene therapy trials funded by the California Institute for Regenerative Medicine. She is passionate about helping parents of children with SCID navigate treatment options for their child.
At CIRM we are privileged to work with many remarkable people who combine brilliance, compassion and commitment to their search for new therapies to help people in need. One of those who certainly fits that description is UC Davis’ Jan Nolta.
This week the UC Davis Newsroom posted a great interview with Jan. Rather than try and summarize what she says I thought it would be better to let her talk for herself.
Talking research, unscrupulous clinics, and sustaining the momentum
In 2007, Jan Nolta
returned to Northern California from St. Louis to lead what was at the
time UC Davis’ brand-new stem cell program. As director of the UC Davis Stem Cell Program
and the Institute for Regenerative Cures, she has overseen the opening
of the institute, more than $140 million in research grants, and dozens
upon dozens of research studies. She recently sat down to answer some
questions about regenerative medicine and all the work taking place at UC Davis Health.
Q: Turning stem cells into cures has been your mission and mantra since you founded the program. Can you give us some examples of the most promising research?
I am so excited about our research. We have about 20 different disease-focused teams.
That includes physicians, nurses, health care staff, researchers and
faculty members, all working to go from the laboratory bench to
patient’s bedside with therapies.
Perhaps the most promising and
exciting research right now comes from combining blood-forming
stem cells with gene therapy. We’re working in about
eight areas right now, and the first cure, something that we definitely
can call a stem cell “cure,” is coming from this combined approach.
doctors will be able to prescribe this type of stem cell therapy.
Patients will use their own bone marrow or umbilical cord stem cells.
Teams such as ours, working in good manufacturing practice
facilities, will make vectors, essentially “biological delivery
vehicles,” carrying a good copy of the broken gene. They will be
reinserted into a patient’s cells and then infused back into the
patient, much like a bone marrow transplant.
“Perhaps the most promising and exciting research right now comes from combining blood-forming stem cells with gene therapy.”
Along with treating the famous bubble baby disease,
where I had started my career, this approach looks very promising for
sickle cell anemia. We’re hoping to use it to treat several different
inherited metabolic diseases. These are conditions characterized by an
abnormal build-up of toxic materials in the body’s cells. They interfere
with organ and brain function. It’s caused by just a single enzyme.
Using the combined stem cell gene therapy, we can effectively put a good
copy of the gene for that enzyme back into a patient’s bone marrow stem
cells. Then we do a bone marrow transplantation and bring back a
person’s normal functioning cells.
The beauty of this therapy is
that it can work for the lifetime of a patient. All of the blood cells
circulating in a person’s system would be repaired. It’s the number one
stem cell cure happening right now. Plus, it’s a therapy that won’t be
rejected. These are a patient’s own stem cells. It is just one type of
stem cell, and the first that’s being commercialized to change cells
throughout the body.
Q: Let’s step back for a moment. In 2004, voters approved Proposition 71.
It has funded a majority of the stem cell research here at UC Davis and
throughout California. What’s been the impact of that ballot measure
and how is it benefiting patients?
We have learned so
much about different types of stem cells, and which stem cell will be
most appropriate to treat each type of disease. That’s huge. We had to
first do that before being able to start actual stem cell therapies. CIRM [California Institute for Regenerative Medicine] has funded Alpha Stem Cell Clinics.
We have one of them here at UC Davis and there are only five in the
entire state. These are clinics where the patients can go for
high-quality clinical stem cell trials approved by the FDA
[U.S. Food and Drug Administration]. They don’t need to go to
“unapproved clinics” and spend a lot of money. And they actually
“By the end of this year, we’ll have 50 clinical trials.”
By the end of this year, we’ll have 50 clinical trials [here at UC Davis Health]. There are that many in the works.
Our Alpha Clinic
is right next to the hospital. It’s where we’ll be delivering a lot of
the immunotherapies, gene therapies and other treatments. In fact, I
might even get to personally deliver stem cells to the operating room
for a patient. It will be for a clinical trial involving people who have
broken their hip. It’s exciting because it feels full circle, from
working in the laboratory to bringing stem cells right to the patient’s
We have ongoing clinical trials
for critical limb ischemia, leukemia and, as I mentioned, sickle cell
disease. Our disease teams are conducting stem cell clinical trials
targeting sarcoma, cellular carcinoma, and treatments for dysphasia [a
swallowing disorder], retinopathy [eye condition], Duchenne muscular
dystrophy and HIV. It’s all in the works here at UC Davis Health.
also great potential for therapies to help with renal disease and
kidney transplants. The latter is really exciting because it’s like a
mini bone marrow transplant. A kidney recipient would also get some
blood-forming stem cells from the kidney donor so that they can better
accept the organ and not reject it. It’s a type of stem cell therapy
that could help address the burden of being on a lifelong regime of
immunosuppressant drugs after transplantation.
Q: You and
your colleagues get calls from family members and patients all the
time. They frequently ask about stem cell “miracle” cures. What should
people know about unproven treatments and unregulated stem cell clinics?
That’s a great question.The number one rule is that if
you’re asked to pay money for a stem cell treatment, don’t do it. It’s a
big red flag.
When it comes to advertised therapies: “The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.”
there are unscrupulous people out there in “unapproved clinics” who
prey on desperate people. What they are delivering are probably not even
stem cells. They might inject you with your own fat cells, which
contain very few stem cells. Or they might use treatments that are not
matched to the patient and will be immediately rejected. That’s
dangerous. The FDA is shutting these unregulated clinics down one at a
time. But it’s like “whack-a-mole”: shut one down and another one pops
On the other hand, the Alpha Clinic is part of our
mission is to help the public get to the right therapy, treatment or
clinical trial. The big difference between those who make patients pay
huge sums of money for unregulated and unproven treatments and UC Davis
is that we’re actually using stem cells. We produce them in rigorously
regulated cleanroom facilities. They are certified to contain at least 99% stem cells.
and family members can always call us here. We can refer them to a
genuine and approved clinical trial. If you don’t get stem cells at the
beginning [of the clinical trial] because you’re part of the placebo
group, you can get them later. So it’s not risky. The placebo is just
saline. I know people are very, very desperate. But there are no miracle
cures…yet. Clinical trials, approved by the FDA, are the only way we’re
going to develop effective treatments and cures.
Scientific breakthroughs take a lot of patience and time. How do you and
your colleagues measure progress and stay motivated?
Motivation? “It’s all for the patients.”
all for the patients. There are not good therapies yet for many
disorders. But we’re developing them. Every day brings a triumph.
Measuring progress means treating a patient in a clinical trial, or
developing something in the laboratory, or getting FDA approval. The big
one will be getting biological license approval from the FDA, which
means a doctor can prescribe a stem cell or gene therapy treatment. Then
it can be covered by a patient’s health insurance.
I’m a cancer
survivor myself, and I’m also a heart patient. Our amazing team here at
UC Davis has kept me alive and in great health. So I understand it from
both sides. I understand the desperation of “Where do I go?” and “What
do I do right now?” questions. I also understand the science side of
things. Progress can feel very, very slow. But everything we do here at
the Institute for Regenerative Cures is done with patients in mind, and
We know that each day is so important when you’re watching
a loved one suffer. We attend patient events and are part of things
like Facebook groups, where people really pour their hearts out. We say
to ourselves, “Okay, we must work harder and faster.” That’s our
motivation: It’s all the patients and families that we’re going to help
who keep us working hard.
Battling cancer is always a balancing act. The methods we use – surgery, chemotherapy and radiation – can help remove the tumors but they often come at a price to the patient. In cases where the cancer has spread to the bone the treatments have a limited impact on the disease, but their toxicity can cause devastating problems for the patient. Now, in a CIRM-supported study, researchers at UC Irvine (UCI) have developed a method they say may be able to change that.
Bone metastasis –
where cancer starts in one part of the body, say the breast, but spreads to the
bones – is one of the most common complications of cancer. It can often result
in severe pain, increased risk of fractures and compression
of the spine. Tackling them is difficult because some cancer cells can
alter the environment around bone, accelerating the destruction of healthy bone
cells, and that in turn creates growth factors that stimulate the growth of the
cancer. It is a vicious cycle where one problem fuels the other.
Now researchers at
UCI have developed a method where they combine engineered mesenchymal stem cells (taken from the bone marrow) with
targeting agents. These act like a drug delivery device, offloading
different agents that simultaneously attack the cancer but protect the bone.
In a news release Weian Zhao, lead author of the study, said:
“What’s powerful about this
strategy is that we deliver a combination of both anti-tumor and anti-bone
resorption agents so we can effectively block the vicious circle between
cancers and their bone niche. This is a safe and almost nontoxic treatment
compared to chemotherapy, which often leaves patients with lifelong issues.”
published in the journal EBioMedicine,
has already been shown to be effective in mice. Next, they hope to be able to
do the safety tests to enable them to apply to the Food and Drug Administration
for permission to test it in people.
The team say if this
approach proves effective it might also be used to help treat other bone-related
diseases such as osteoporosis and multiple myeloma.