This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two additional discovery research projects as part of the $5 million in emergency funding for COVID-19 related projects. This brings the number of COVID-19 projects CIRM is supporting to 15, including three clinical trials.
The Board awarded $249,999 to Dr. Evan Snyder at the Sanford Burnham Prebys Medical Discovery Institute. The study will use induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids. These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treatment of the virus. The iPSCs and the subsequent lung organoids created will reflect diversity by including male and female patients from the Caucasian, African-American, and Latinx population.
This award is part of CIRM’s Quest Awards Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.
The Board also awarded $150,000 to Dr. Steven Dowdy at UC San Diego for development of another potential treatment for COVID-19.
Dr. Dowdy and his team are working on developing a new, and hopefully more effective, way of delivering a genetic medicine, called siRNA, into the lungs of infected patients. In the past trying to do this proved problematic as the siRNA did not reach the appropriate compartment in the cell to become effective. However, the team will use an iPSC lung model to help them identify ways past this barrier so the siRNA can attack the virus and stop it replicating and spreading throughout the lungs.
This award is part of CIRM’s Inception Awards Program (DISC1), which supports transformational ideas that require the generation of additional data.
A supplemental award of $250,000 was approved for Dr. John Zaia at City of Hope to continue support of a CIRM funded clinical study that is using convalescent plasma to treat COVID-19 patients. The team recently launched a website to enroll patients, recruit plasma donors, and help physicians enroll their patients.
“The use of induced pluripotent stem cells has expanded the potential for personalized medicine,” says Dr. Maria T. Millan, the President & CEO of CIRM. “Using patient derived cells has enabled researchers to develop lung organoids and lung specific cells to test numerous COVID-19 therapies.”
Sometimes it’s the smallest things that make the biggest difference. In the case of a clinical trial that CIRM is funding, all it takes to be part of it is four teaspoons of blood.
The clinical trial is being run by Dr. John Zaia and his team at the City of Hope in Duarte, near Los Angeles, in partnership with tgen and the CIRM Alpha Stem Cell Clinic Network. They are going to use blood plasma from people who have recovered from COVID-19 to treat people newly infected with the virus. The hope is that antibodies in the plasma, which can help fight infections, will reduce the severity or length of infection in others.
People who have had the virus and are interested in taking part are asked to give four teaspoons of blood, to see if they have enough antibodies. If they do they can then either donate plasma – to help newly infected people – or blood to help with research into COVID-19.
As a sign of how quickly Dr. Zaia and his team are working, while we only approved the award in late April, they already have their website up and running, promoting the trial and trying to recruit both recovered COVID-19 survivors and current patients.
The site does a great job of explaining what they are trying to do and why people should take part. Here’s one section from the site.
Why should I participate in your study?
By participating in our study, you will learn whether you have developed antibodies against SARS-CoV-2, the virus responsible for COVID-19. To do so, you just need to donate a small sample of blood (approximately 4 teaspoons).
If testing show you have enough antibodies, you will have the option of donating plasma that will be used to treat severely ill COVID-19 patients and may help save lives.
If you don’t want to donate plasma, you can still donate blood (approximately 3.5 tablespoons), which will be studied and help researchers learn more about COVID-19.
By donating blood or plasma, you will help us gain information that may be of significant value for patient management in future epidemic seasons.
You don’t even have to live close to one of the clinical trial sites because the team can send you a blood collection kit and information about a blood lab near you so you can donate there. They may even send a nurse to collect your blood.
The team is also trying to ensure they reach communities that are often overlooked in clinical trials. That’s why the website is also in Spanish and Vietnamese.
Finally, the site is also being used to help recruit treating physicians who can collect the blood samples and help infuse newly infected patients.
We often read about clinical trials in newspapers and online. Now you get a chance to not only see one working in real time, you can get to be part of it.
There is still a lot that we don’t understand about SARS-CoV-2 (COVID-19), the new coronavirus that has caused a worldwide pandemic. Some patients that contract the virus experiences heart problems, but the reasons are not entirely clear. Pre-existing heart conditions or inflammation and oxygen deprivation that result from COVID-19 have all been implicated but more evidence needs to be collected.
To evaluate this, a joint study between Cedars-Sinai Board of Governors Regenerative Medicine Institute and the UCLA Broad Stem Cell Research Center used human induced pluripotent stem cells (iPSCs), a kind of stem cell that can become any kind of cell in the body and is usually made from skin cells. The iPSCS were converted into heart cells and infected with COVID-19 in order to study the effects of the virus.
The results of this study showed that the iPSC-derived heart cells are susceptible to COVID-19 infection and that the virus can quickly divide inside the heart cells. Furthermore, the infected heart cells showed changes in their ability to beat 72 hours after infection.
In a press release, Dr. Clive Svendsen, senior and co-corresponding author of the study and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, elaborated on the results.
“This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmias, heart failure and viral myocarditis. While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in COVID-19.”
Although this study does not perfectly replicate the conditions inside the human body, the iPSC heart cells may also help identify and screen new potential drugs that could alleviate viral infection of the heart.
The research team has already found that treatment with an antibody called ACE2 was able to decrease viral replication on the iPSC heart cells.
In the same press release Dr. Arun Sharma, first author and another co-corresponding author of the study and a research fellow at the Cedars-Sinai Board of Governors Regenerative Medicine Institute, had this to say about the ACE2 antibody.
“By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell. This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection.”
The study’s third co-corresponding author was Dr. Vaithilingaraja Arumugaswami, an associate professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
The full results of this study were published in Cell Reports Medicine.
In the addition to the innovative scientists and clinicians who conceive and develop novel experimental therapies, it takes a village to drive a promising experimental therapy through phases of clinical trials, regulatory marketing approval, and commercialization before it becomes broadly accessible to patients with unmet medical needs. In this case, the village is the broader industry including institutional investors and biopharma companies that have the capital, resources and expertise to carry the development programs past the finish line.
A big part of what CIRM does revolves around nurturing projects at the very early stages. By providing funding and guidance through our collaborative team of experts, CIRM de-risks its therapy development programs through pre-clinical and clinical stages, thereby readying them for industry partnerships to support them through the last mile. CIRM funding to California academic institutions has enabled the launch of more than 40 spinout companies, one of which we will highlight below.
On April 7th, 2020, Forty Seven, Inc. was acquired by Gilead Sciences for $4.9 billion. CIRM funded the preclinical and early clinical development of an anti-CD47 antibody candidate for cancer at Stanford and subsequently funded two Forty Seven clinical trials. Now, Gilead will leverage all of its resources to accelerate the development of this promising cancer immunotherapy.
Dr. Mark Chao, Co-Founder, Forty Seven, Inc. had this to say about CIRM.
“CIRM’s support has been instrumental to our early successes and our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach with magrolimab. CIRM was an early collaborator in our clinical programs and it’s support was instrumental in helping us reach a point where we could become a part of Gilead and move forward with our research.”
To proactively enable more partnering successes such as Forty Seven, CIRM has established the Industry Alliance Program (IAP) as a direct opportunity for the industry to partner with CIRM grantees in accelerating the most promising stem cell, gene and regenerative medicine therapy programs to commercialization. Through the IAP, CIRM is a dedicated and proactive partner to industry and CIRM grantees.
We recently launched a website for those interested in knowing more about these partnerships. It describes the IAP program in more detail can be accessed by clicking here.
If you are a potential industry partner wishing to learn more about CIRM’s IAP, please contact:
There are some people who, when you think of them, always bring a smile to your face. Dr. Bert Lubin was one of those people. Sadly, we lost Bert to brain cancer two days ago. But the impact he had, not just as an advocate for stem cell research but as a pioneer in sickle cell disease research and a champion for children’s health, will live on.
Bert had a number of official titles but probably the one he was most proud of was President & CEO of Children’s Hospital Oakland (now UCSF Benioff Children’s Hospital Oakland). But it wasn’t the title that he cared about, it was the opportunity it gave him to make a difference in the life of children in Oakland, to create a program to find new treatments and cures for a life-threatening disease. And he has made a difference.
As I started to write this tribute to Bert, I thought about who I should ask for a quote. And then I realized I had the perfect person. Bert himself. I was fortunate enough to interview him in December 2018, when he decided to step down after eight years on the CIRM Board. As always, he had his own positive spin on that, saying: “I don’t see myself leaving. I’m just repurposing what is my role in CIRM. I’m recycling and reinventing.”
And Bert was always full of invention.
He grew up in Bellevue, a small town outside Pittsburgh, PA. His parents ran a fruit and vegetable market there and, growing up, Bert often worked in the store. It wasn’t something he enjoyed but he said he learned some valuable lessons.
“I think what happened in my childhood is that I learned how to sell. I am a salesman. I hated working in that store, I hated it, but I liked the communication with people, they trusted me, I could sell things and they were good things. Like Christmas. I’m Jewish, we were the only Jews in that community, and at Christmas we sold Christmas trees, but the trees were sometimes crooked and they were $2.99 a tree so I convinced families that I could go to their house and set the tree so it looked straight and I helped them decorate it and they loved it.”
He said, thinking back on his life it’s almost as if there were a plan, even if he wasn’t aware of it.
“I started thinking about that more recently, I started wondering how did this even happen? I’m not a religious person but it’s almost like there’s some fate. How did I get there? It’s not that I planned it that way and it’s certainly not that my parents planned it because I was the first in my family to go to high school let alone college. My parents, when I went to medical school and then decided I wanted to spend more time in an academic direction, they were upset. They wanted me to go into practice in a community that I grew up in and be economically secure and not be on the fringe in what an academic life is like.”
And then, fate stepped in and brought him to the San Francisco Bay Area.
“What happened was, I was at the University of Pennsylvania having trained at Boston Children’s and Philadelphia Children’s, where I had started a sickle cell disease program, and was asked to look at a job in southern California to start a sickle cell program there. So, I flew to San Francisco because a lot of people I’d studied with were now working at UCSF and I thought it would be fun to see them before going down to southern California. They took me out to dinner and showed me around and I said this place is beautiful, I can play tennis out here all year round, there’s lots of music – I love jazz – and they said ‘you know Bert, have you looked at Oakland Children’s hospital? We want to start a sickle cell program center, but the patients are all in Oakland and the patient population that would be served is in Oakland. But if you came out to the Bay Area we could partner with you to start that program.
“So, when I walked in the door here (at Oakland) and said ‘I want to create this northern California sickle cell center with UC’ the staff that was here said ‘you know we’re not a research hospital, we are a community based hospital’. I said, ‘I’m not saying you shouldn’t be that but I’m trying to create an opportunity here’ and they said to me ‘as long as you don’t ask for any money you can go and do whatever you want’.
‘They recognized that I had this fire in me to really create something that was novel. And the warmth and community commitment from this place is something that attracted me and then allowed me to build on that.
“For example, when I became the director of the research program we had $500,000 in NIH grants and when I left we had $60 million. We just grew. Why did we grow? Because we cared about the faculty and the community. We had a lovely facility, which was actually the home of the Black Panther party. It was the Black Panthers who started screening for sickle cell on street corners here in Oakland, and they were the start of the national sickle cell act so there’s a history here and I like that history.
“Then I got a sense of the opportunities that stem cell therapies would have for a variety of things, certainly including sickle cell disease, and I thought if there’s a chance to be on the CIRM Board, as an advocate for that sickle cell community, I think I’d be a good spokesperson. So, I applied. I just thought this was an exciting opportunity.
“I thought it was a natural fit for me to add some value, I only want to be on something where I think I add value.”
Bert added value to everything he did. And everyone he met felt valued by him. He was a mentor to so many people, young physicians and nurses, students starting out on their careers. And he was a friend to those in need.
He was an extraordinary man and we are grateful that we were able to call him a colleague, and a friend, for as long as we did.
When Burt stepped down from Children’s his colleagues put together this video about his life and times. It seems appropriate to share it again and remind ourselves of the gift that he was to everyone fortunate enough to know him.
Now that we have 64 clinical trials that we have funded (plus a few dozen more where we supported the early stage research) it’s sometimes hard to remember the details of each trial. But there is one you never forget. The very first clinical trial you funded. And we just got some encouraging news about it.
Way back in 2011 CIRM funded a clinical trial with a company called Geron, targeting spinal cord injuries. It was not only the first clinical trial we funded, it was also the first clinical trial involving the use of embryonic stem cells that was approved by the US Food and Drug Administration (FDA).
But in November of that year Geron decided to change its business plan and canceled the trial. We got all our money back – plus interest – but it was still terribly disappointing to us and to everyone who had hopes the research would help people with severe spinal cord injuries.
Fast forward three years and a company called Asterias picked up where Geron left off, getting permission from the FDA to run a clinical trial using the same approach for spinal cord injuries. Once again CIRM funded the project.
We profiled two of the patients treated in this group who seemed to benefit a lot from the therapy; Jake Javier and Kris Boesen.
But after the initial trial it felt like someone hit the pause button. Asterias was bought up by BioTime which changed its name to Lineage Cell Therapeutics and moved much of the OPC1 spinal cord injury program to Israel. Then last week Lineage announced it was unpausing the program.
In a news release they announced that by moving the program to their cGMP manufacturing plant in Israel they were able to make “process improvements” in the program and, more importantly; “ Lineage intends to meet with the U.S. Food and Drug Administration (FDA) to discuss further development of the OPC1 program by the end of 2020.”
Brian M. Culley, Lineage’s CEO said: “We have worked diligently over the past year to transition all manufacturing activities for the OPC1 program to our in-house cGMP facility, where our experienced cell therapy production team could develop and deploy much-needed improvements and modernization to the production and analytical processes. This work has achieved significantly better efficiency and improved quality control, which we expect will enable a consistent supply of material to support a late-stage clinical trial of OPC1. With these necessary steps now completed, our focus turns to developing a “thaw-and-inject” formulation and superior delivery tools, to enable an easier surgical procedure and facilitate faster enrollment in the next clinical trial. We also are evaluating ways to return OPC1 to the clinic sooner than originally planned, reflecting our view of compelling clinical data which continues to read out from the 25-patient phase 1/2a SCiStar study.”
So, almost a decade after we first became involved with this project, we’re happy to say it’s alive and seemingly well and getting ready to take the next step in helping people with spinal cord injuries. We’ll let you know how it goes.
One last thing. One of the reasons we are such fans of the approach is Jake Javier. We have come to know and admire him and watch him fight back from his injury. He is a remarkable young man in many ways. He is now a student at Cal Poly where they made this video about him.
Today the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $750,000 to Dr. Xiaokui Zhang at Celularity to conduct a clinical trial for the treatment of COVID-19. This brings the total number of CIRM clinical trials to 64, including three targeting the coronavirus.
This trial will use blood stem cells obtained from the placenta to generate natural killer (NK) cells, a type of white blood cell that is a vital part of the immune system, and administer them to patients with COVID-19. NK cells play an important role in defense against cancer and in fighting off viral infections. The goal is to administer these cells to locate the active sites of COVID-19 infection and destroy the virus-infected cells. These NK cells have been used in two other clinical trials for acute myeloid leukemia and multiple myeloma.
The Board also approved two additional awards for Discovery Stage Research (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.
One award for $100,000 was given to Dr. Albert Wong at Stanford. Dr. Wong has recently received an award from CIRM to develop a vaccine that produces a CD8+ T cell response to boost the body’s immune response to remove COVID-19 infected cells. The current award will enable him to expand on the initial approach to increase its potential to impact the Latinx and African American populations, two ethnicities that are disproportionately impacted by the virus in California.
The other award was for $249,996 and was given to Dr. Preet Chaudhary at the University of Southern California. Dr. Chaudary will use induced pluripotent stem cells (iPSCs) to generate natural killer cells (NK). These NK cells will express a chimeric antigen receptor (CAR), a synthetic receptor that will directly target the immune cells to kill cells infected with the virus. The ultimate goal is for these iPSC-NK-CAR cells to be used as a treatment for COVID-19.
“These programs address the role of the body’s immune T and NK cells in combatting viral infection and CIRM is fortunate enough to be able to assist these investigators in applying experience and knowledge gained elsewhere to find targeted treatments for COVID-19” says Dr. Maria T. Millan, the President & CEO of CIRM. “This type of critical thinking reflects the resourcefulness of researchers when evaluating their scientific tool kits. Projects like these align with CIRM’s track record of supporting research at different stages and for different diseases than the original target.”
The CIRM Board voted to endorse a new initiative to refund the agency and provide it with $5.5 billion to continue its work. The ‘California Stem Cell Research, Treatments and Cures Initiative of 2020 will appear on the November ballot.
The Board also approved a resolution honoring Ken Burtis, PhD., for his long service on the Board. Dr. Burtis was honored for his almost four decades of service at UC Davis as a student, professor and administrator and for his 11 years on the CIRM Board as both a member and alternate member. In the resolution marking his retirement the Board praised him, saying “his experience, commitment, knowledge, and leadership, contributed greatly to the momentum of discovery and the future therapies which will be the ultimate outcome of the dedicated work of the researchers receiving CIRM funding.”
Jonathan Thomas, the Chair of the Board, said “Ken has been invaluable and I’ve always found him to have tremendous insight. He has served as a great source of advice and inspiration to me and to the ICOC in dealing with all the topics we have had to face.”
Lauren Miller Rogen thanked Dr. Burtis, saying “I sat next to you at my first meeting and was feeling so extraordinarily overwhelmed and you went out of your way to explain all these big science words to me. You were always a source of help and support, and you explained things to me in a way that I always appreciated with my normal brain.”
Dr. Burtis said it has been a real honor and privilege to be on the Board. “I’ve been amazed and astounded at the passion and dedication that the Board and CIRM staff have brought to this work. Every meeting over the years there has been a moment of drama and then resolution and this Board always manages to reach agreement and serve the people of California.”
In late March the CIRM Board approved $5 million in emergency funding for COVID-19 research. The idea was to support great ideas from California’s researchers, some of which had already been tested for different conditions, and see if they could help in finding treatments or a vaccine for the coronavirus.
Less than a month later we were funding a clinical trial and two other projects, one that targeted a special kind of immune system cell that has the potential to fight the virus.
Researchers use stem cells to model the immune response to COVID-19
By Tiare Dunlap
Cities across the United States are opening back up, but we’re still a long way from making the COVID-19 pandemic history. To truly accomplish that, we need to have a vaccine that can stop the spread of infection.
But to develop an effective vaccine, we need to understand how the immune system responds to SARS-CoV-2, the virus that causes COVID-19.
Vaccines work by imitating infection. They expose a person’s immune system to a weakened version or component of the virus they are intended to protect against. This essentially prepares the immune system to fight the virus ahead of time, so that if a person is exposed to the real virus, their immune system can quickly recognize the enemy and fight the infection. Vaccines need to contain the right parts of the virus to provoke a strong immune response and create long-term protection.
Most of the vaccines in development for SARS CoV-2 are using part of the virus to provoke the immune system to produce proteins called antibodies that neutralize the virus. Another way a vaccine could create protection against the virus is by activating the T cells of the immune system.
T cells specifically “recognize” virus-infected cells, and these kinds of responses may be especially important for providing long-term protection against the virus. One challenge for researchers is that they have only had a few months to study how the immune system protects against SARS CoV-2, and in particular, which parts of the virus provoke the best T-cell responses.
For years, they have been perfecting an innovative technology that uses blood-forming stem cells — which can give rise to all types of blood and immune cells — to produce a rare and powerful subset of immune cells called type 1 dendritic cells. Type 1 dendritic cells play an essential role in the immune response by devouring foreign proteins, termed antigens, from virus-infected cells and then chopping them into fragments. Dendritic cells then use these protein fragments to trigger T cells to mount an immune response.
Using this technology, Crooks and Seet are working to pinpoint which specific parts of the SARS-CoV-2 virus provoke the strongest T-cell responses.
Building long-lasting immunity
“We know from a lot of research into other viral infections and also in cancer immunotherapy, that T-cell responses are really important for long-lasting immunity,” said Seet, an assistant professor of hematology-oncology at the David Geffen School of Medicine at UCLA. “And so this approach will allow us to better characterize the T-cell response to SARS-CoV-2 and focus vaccine and therapeutic development on those parts of the virus that induce strong T-cell immunity.”
Crooks’ and Seet’s project uses blood-forming stem cells taken from healthy donors and infected with a virus containing antigens from SARS-CoV-2. They then direct these stem cells to produce large numbers of type 1 dendritic cells using a new method developed by Seet and Suwen Li, a graduate student in Crooks’ lab. Both Seet and Li are graduates of the UCLA Broad Stem Cell Research Center’s training program.
“The dendritic cells we are able to make using this process are really good at chopping up viral antigens and eliciting strong immune responses from T cells,” said Crooks, a professor of pathology and laboratory medicine and of pediatrics at the medical school and co-director of the UCLA Broad Stem Cell Research Center.
When type 1 dendritic cells chop up viral antigens into fragments, they present these fragments on their cell surfaces to T cells. Our bodies produce millions and millions of T cells each day, each with its own unique antigen receptor, however only a few will have a receptor capable of recognizing a specific antigen from a virus.
When a T cell with the right receptor recognizes a viral antigen on a dendritic cell as foreign and dangerous, it sets off a chain of events that activates multiple parts of the immune system to attack cells infected with the virus. This includes clonal expansion, the process by which each responding T cell produces a large number of identical cells, called clones, which are all capable of recognizing the antigen.
“Most of those T cells will go off and fight the infection by killing cells infected with the virus,” said Seet, who, like Crooks, is also a member of the UCLA Jonsson Comprehensive Cancer Center. “However, a small subset of those cells become memory T cells — long-lived T cells that remain in the body for years and protect from future infection by rapidly generating a robust T-cell response if the virus returns. It’s immune memory.”
Producing extremely rare immune cells
This process has historically been particularly challenging to model in the lab, because type 1 dendritic cells are extremely rare — they make up less than 0.1% of cells found in the blood. Now, with this new stem cell technology, Crooks and Seet can produce large numbers of these dendritic cells from blood stem cells donated by healthy people, introduce them to parts of the virus, then see how T cells taken from the blood can respond in the lab. This process can be repeated over and over using cells taken from a wide range of healthy people.
“The benefit is we can do this very quickly without the need for an actual vaccine trial, so we can very rapidly figure out in the lab which parts of the virus induce the best T-cell responses across many individuals,” Seet said.
The resulting data could be used to inform the development of new vaccines for COVID-19 that improve T-cell responses. And the data about which viral antigens are most important to the T cells could also be used to monitor the effectiveness of existing vaccine candidates, and an individual’s immune status to the virus.
“There are dozens of vaccine candidates in development right now, with three or four of them already in clinical trials,” Seet said. “We all hope one or more will be effective at producing immediate and long-lasting immunity. But as there is so much we don’t know about this new virus, we’re still going to need to really dig in to understand how our immune systems can best protect us from infection.”
Supporting basic research into our body’s own processes that can inform new strategies to fight disease is central to the mission of the Broad Stem Cell Research Center.
“When we started developing this project some years ago, we had no idea it would be so useful for studying a viral infection, any viral infection,” Crooks said. “And it was only because we already had these tools in place that we could spring into action so fast.”
If that headline seems familiar it should. It came from an article in MIT Technology Review back in 2009. There have been many other headlines since then, all on the same subject, and yet here we are, in 2020, and still no cure for HIV/AIDS. So what’s the problem, what’s holding us back?
First, the virus is incredibly tough and wily. It is constantly mutating so trying to target it is like playing a game of ‘whack a mole’. Secondly not only can the virus evade our immune system, it actually hijacks it and uses it to help spread itself throughout the body. Even new generations of anti-HIV medications, which are effective at controlling the virus, can’t eradicate it. But now researchers are using new tools to try and overcome those obstacles and tame the virus once and for all.
UCLA researchers Scott Kitchen and Irvin Chen have been awarded $13.65 million by the National Institutes of Health (NIH) to see if they can use the patient’s own immune system to fight back against HIV.
Dr. Kitchen and Dr. Chen take the patient’s own blood-forming stem cells and then, in the lab, they genetically engineer them to carry proteins called chimeric antigen receptors or CARs. Once these blood cells are transplanted back into the body, they combine with the patient’s own immune system T cells (CAR T). These T cells now have a newly enhanced ability to target and destroy HIV.
That’s the theory anyway. Lots of research in the lab shows it can work. For example, the UCLA team recently showed that these engineered CAR T cells not only destroyed HIV-infected cells but also lived for more than two years. Now the team at UCLA want to take the lessons learned in the lab and apply them to people.
In a news release Dr. Kitchen says the NIH grant will give them a terrific opportunity to do that: “The overarching goal of our proposed studies is to identify a new gene therapy strategy to safely and effectively modify a patient’s own stem cells to resist HIV infection and simultaneously enhance their ability to recognize and destroy infected cells in the body in hopes of curing HIV infection. It is a huge boost to our efforts at UCLA and elsewhere to find a creative strategy to defeat HIV.”
By the way, CIRM helped get this work off the ground with an early-stage grant. That enabled Dr. Kitchen and his team to get the data they needed to be able to apply to the NIH for this funding. It’s a great example of how we can kick-start projects that no one else is funding. You can read a blog about that early stage research here.
Although some broken bones can be mended with the help of a cast, others require more complex treatments. Bone grafts, which can come from the patient’s own body or a donor, are used to transplant bone tissue to the injury site. However, these procedures can have setbacks such as increased recovery time and chronic pain. Each year approximately 600,000 people in the United States alone experience complications from bone healing.
Researchers at Texas A&M University found a way to use induced pluripotent stem cells (iPSCs), a type of stem cell that can turn into any cell type and can be derived from adults cells (e.g. skin cells), to create superior bone grafts. The team of researchers said these grafts could potentially be used to promote swift and precise bone healing, enabling patients to optimally benefit from surgical intervention.
The Texas A&M team used iPSCS to make mesenchymal stem cells (MSCs), which make the extracellular matrix needed for bone grafts. MSCs can be obtained from bone marrow, but they have a relatively shorter life span and are not as biologically active when compared to MSCs generated from iPSCs.
To test the effectiveness of their iPSC generated bone grafts, they implanted the extracellular matrix at a site of bone defects. After a few weeks, they found that their iPSC generated matrix was five to sixfold more effective than the best FDA-approved graft stimulator.
In a news release from Texas A&M, Dr. Roland Kaunas discusses the potential benefits of using iPSC generated bone grafts.
“Our material is very promising because the pluripotent stem cells can ideally generate many batches of the extracellular matrix from just a single donor which will greatly simplify the large-scale manufacturing of these bone grafts.”
Additionally, the Texas A&M team said this approach has the potential to be incorporated into numerous engineered implants, such as 3D-printed implants or metal screws, so that these parts integrate better with the surrounding bone.
The full results of this study were published in Nature Communications.
A brief video on bone grafts from Texas A&M is available below.