Zika is caused by a virus that is mainly transmitted by infected female Aedes aegypti mosquitoes but also through sexual intercourse. People infected by Zika virus usually have mild symptoms that normally last for two to seven days and can include fever, skin rashes, conjunctivitis, muscle and joint pain, or headaches.
Zika also causes devastating congenital neurodefective disorders, most notably microcephaly, where a child’s head is much smaller than expected, in children born to infected mothers as well as neurological problems in those infected like Guillain-Barré syndrome.
To date, no vaccines or other treatments have been approved for Zika virus. Nor have investigations into other ways of fighting the virus led to clearly effective countermeasures.
But there is good news. Researchers from the University of California, Los Angeles (UCLA) have developed a Zika vaccine technology that is both highly effective and safe in preclinical mouse models. The study—partially funded by the California Institute for Regenerative Medicine (CIRM)—found that in a pregnant mouse model, the vaccine prevented both the pregnant mothers and the developing fetuses from developing systemic infection.
In engineering the vaccine, researchers deleted the part of the Zika genome that codes for the viral shell, the protective shell that a virus forms to evade the immune system. “This modification both stimulates an immunogenic reaction and prevents the virus from replicating and spreading from cell to cell,” said Vaithilingaraja Arumugaswami, D.V.M., Ph.D., Associate Professor of Molecular and Medical Pharmacology at UCLA.
This is important progress because the average length of time between periods of extensive Zika viral spread is approximately 7 years. Given that the virus was last widespread in 2016, “it is only a matter of time before we start seeing the virus spread again,” said Kouki Morizono, M.D., Ph.D., Associate Professor of Medicine at UCLA and co-senior author of this study.
“The ongoing COVID-19 pandemic has shown us the power of a strong pandemic preparedness plan and clear communication about prevention methods – all culminating in the rapid rollout of safe and reliable vaccines. Our research is a crucial first step in developing an effective vaccination program that could curb the spread of Zika virus and prevent large-scale spread from occurring,” said Arumugaswami.
To try and boost sales during the pandemic many businesses are offering two-for-one deals; buy one product get another free. Well, that might also be the case with a flu shot; get one jab and get protection from two viruses.
A new study offers an intriguing – though not yet certain – suggestion that getting a flu shot could not only reduce your risk of getting the flu, but also help reduce your risk of contracting the coronavirus. If it’s true it would be a wonderful tool for health professionals hoping to head of a twindemic of flu and COVID-19 this winter. It would also be a pretty sweet deal for the rest of us.
Researchers at Radboud University Medical Center in the Netherlands looked through their hospital’s database and compared people who got a flu shot during the previous year with people who didn’t. They found that people who got the vaccine were 39 percent less likely to have tested positive for the coronavirus than people who didn’t get the vaccine.
Now, there are a bunch of caveats about this study (published in the preprint journal MedRxiv) one of which is that it wasn’t peer reviewed. Another is that people who get flu shots might just be more health conscious than people who don’t, which means they might also be more aware of the need to wear a mask, social distance, wash their hands etc.
But that doesn’t mean this study is wrong. Two recent studies (in the journal Vaccines and the Journal of Medical Virology) also found similar findings, that people over the age of 65 who got a flu shot had a lower risk of getting COVID-19. That’s particularly important for that age group as they are the ones most likely to experience life-threatening complications from COVID-19.
But what could explain getting a two-fer from one vaccine? Well, there’s a growing body of research that points to something called “trained innate immunity”. Our bodies have two different kinds of immune system, adaptive and innate. Vaccines activate the adaptive system, causing it to develop antibodies to attack and kill a virus. But there’s also evidence these same vaccines could trigger our innate immune system to help fight off infections. So, a flu vaccine could boost your adaptive immunity against the flu, but also kick in the innate immunity against the coronavirus.
In an article in Scientific American, Ellen Foxman, an immunobiologist and clinical pathologist at the Yale School of Medicine, says that might be the case here: “There is evidence from the literature that trained immunity does exist and can offer broad protection, in unexpected ways, against other pathogens besides what the vaccine was designed against.”
The researchers in the Netherlands wanted to see if there was any evidence that what they saw in their hospital had any basis in fact. So, they devised a simple experiment. They took blood cells from healthy individuals and exposed some of the cells to the flu vaccine. After six days they exposed all the cells to the SARS-CoV-2, the virus that causes COVID-19.
Compared to the untreated cells, the cells that had been exposed to the flu vaccine produced more virus-fighting immune molecules called cytokines. These can attack the virus and help protect people early on, resulting in a milder, less dangerous infection.
All in all it’s encouraging evidence that a flu shot might help protect you against the coronavirus. And at the very least it will reduce your risk of the flu, and if there’s one thing you definitely don’t want this year it’s having to battle two life-threatening viruses at the same time.
It’s been a long time coming. Eighteen months to be precise. Which is a peculiarly long time for an Annual Report. The world is certainly a very different place today than when we started, and yet our core mission hasn’t changed at all, except to spring into action to make our own contribution to fighting the coronavirus.
This latest CIRM Annual Reportcovers 2019 through June 30, 2020. Why? Well, as you probably know we are running out of money and could be funding our last new awards by the end of this year. So, we wanted to produce as complete a picture of our achievements as we could – keeping in mind that we might not be around to produce a report next year.
It’s a pretty jam-packed report. It covers everything from the 14 new clinical trials we have funded this year, including three specifically focused on COVID-19. It looks at the extraordinary researchers that we fund and the progress they have made, and the billions of additional dollars our funding has helped leverage for California. But at the heart of it, and at the heart of everything we do, are the patients. They’re the reason we are here. They are the reason we do what we do.
There are stories of people like Byron Jenkins who almost died from multiple myeloma but is now back leading a full, active life with his family thanks to a CIRM-funded therapy with Poseida. There is Jordan Janz, a young man who once depended on taking 56 pills a day to keep his rare disease, cystinosis, under control but is now hoping a stem cell therapy developed by Dr. Stephanie Cherqui and her team at UC San Diego will make that something of the past.
These individuals are remarkable on so many levels, not the least because they were willing to be among the first people ever to try these therapies. They are pioneers in every sense of the word.
There is a lot of information in the report, charting the work we have done over the last 18 months. But it’s also a celebration of everyone who made it possible, and our way of saying thank you to the people of California who gave us this incredible honor and opportunity to do this work.
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.”
Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.
Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.
This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.
“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”
The Board also approved two early stage research projects targeting COVID-19.
Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.
“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”
The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients
SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy. Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.
Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.
“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”
In response to the crisis caused by the COVID-19 virus in California and around the world the governing Board of the California Institute for Regenerative Medicine (CIRM) today held an emergency meeting to approve $5 million in rapid research funds targeting the virus.
“These are clearly extraordinary times and they require an extraordinary response from all of us,” says Dr. Maria T. Millan, President and CEO of CIRM. “Our mission is to accelerate stem cell treatments to patients with unmet medical needs. California researchers have made us aware that they are pursuing potential stem cell based approaches to the COVID-19 crisis and we felt it was our responsibility to respond by doing all we can to support this research and doing so as quickly as we possibly can.”
The Board’s decision enables CIRM to allocate $5 million in funding for peer-reviewed regenerative medicine and stem cell research that could quickly advance treatments for COVID-19. The funding will be awarded as part of an expedited approval process.
To qualify applicants would go through a full review by CIRM’s independent Grants Working Group.
Approved projects will be immediately forwarded to the CIRM Board for a vote
Projects approved by the Board would go through an accelerated contract process to ensure funds are distributed as quickly as possible
“Our hope is that we can go from application to funding within 30 to 40 days,” says Jonathan Thomas, PhD, JD, Chair of the CIRM Board. “This is a really tight timeframe, but we can’t afford to waste a moment. There is too much at stake. The coronavirus is creating an unprecedented threat to all of us and, as one of the leading players in regenerative medicine, we are committed to doing all we can to develop the tools and promote the research that will help us respond to that threat.”
Only projects that target the development or testing of a treatment for COVID-19 are eligible. They must also meet other requirements including being ready to start work within 30 days of approval and propose achieving a clear deliverable within six months. The proposed therapy must also involve a stem cell or a drug or antibody targeting stem cells.
The award amounts and duration of the award are as follows:
Award Amount and Duration Limits
Late stage preclinical
CIRM Board members were unanimous in their support for the program. Al Rowlett, the patient advocate for mental health, said: “Given the complexity of this situation and the fact that many of the individuals I represent aren’t able to advocate for themselves, I wholeheartedly support this.”
Dr. Os Steward, from UC Irvine agreed: “I think that this is a very important thing for CIRM to do for a huge number of reasons. The concept is great and CIRM is perfectly positioned to do this.”
“All hands are on deck world-wide in this fight against COVID-19.” says Dr. Millan. “CIRM will deploy its accelerated funding model to arm our stem cell researchers in this multi-pronged and global attack on the virus.”
In the United States alone, there are approximately 1.1 million people living with Human immunodeficiency virus (HIV), a virus that weakens the immune system by destroying important cells that fight off disease and infection. This number is much larger on a global scale, with 36.9 million people living with HIV as of 2017. If left untreated, the immune system becomes so weakened that the condition worsens into acquired immunodeficiency syndrome (AIDS), which is usually fatal.
Current treatment for HIV focuses on the use of antiretroviral therapy (ART). This treatment is able to suppress replication of the virus, but it does not eliminate it from the body entirely. In order to be sustainable, ART must be taken throughout the course of a lifetime, otherwise HIV rebounds and the replication of the virus renews, fueling the development of AIDS.
The ability of HIV to rebound is related to the fact that it is able to integrate its DNA into various cells inside the body and beyond the reach of ART. Here they are able to remain dormant and ready to replicate as soon as ART is not interfering. It is because of this that ART is not sufficient on its own to cure HIV, but a group of scientists have uncovered a promising breakthrough to change that.
In a major collaboration, researchers at the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC) have for the first time eliminated HIV from the DNA of living mice. This study marks a critical step toward the development of a possible cure for human HIV infection.
The team of researchers was able to do this with the help of a new technology called long-acting slow-effective release (LASER) ART. LASER ART is able to target HIV sanctuaries and maintain replication at low levels for extended periods of time. Immediately after administering LASER ART, the team used a gene editing technology known as CRISPR to remove the final remnants of HIV DNA hidden inside cells.
In a press release, Dr. Kamel Khalili, senior investigator for this study, was quoted as saying,
“Our study shows that treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals…We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year.”
The full results of this study were published in Nature Communications.
To learn more about how CRISPR technology works, you can read more about it on a previous blog post.
This week’s awesome stem cell photo comes with a bizarre story and bonus video footage.
New research from Duke has found that some lung cancer cells with errors in transcription factors begin to resemble their nearest relatives – the cells of the stomach and gut. (Credit – Tata Lab, Duke University)
Researchers at Duke University were studying lung tumor samples and discovered something that didn’t quite belong. Inside the lung tumors were miniature parts of the digestive system including the stomach, duodenum and small intestine. It turns out that the lung cancer cells (and cancer cells in general) are super crafty and had turned off the expression of a gene called NKX2-1. This gene is a master switch that tells developing cells to turn into lung cells. Without this command, cells switch their identity and mature into gut tissue instead. By manipulating these master switches, cancer cells are able to develop resistance to chemotherapy and other cancer treatments.
So, what does this bizarre finding mean for cancer research? Purushothama Rao Tata, first author on the Developmental Cell study, provided an answer in a news release:
“Cancer biologists have long suspected that cancer cells could shape shift in order to evade chemotherapy and acquire resistance, but they didn’t know the mechanisms behind such plasticity. Now that we know what we are dealing with in these tumors – we can think ahead to the possible paths these cells might take and design therapies to block them.”
For more cool photos and insights into this study, watch the Duke Univeristy video below.
Secrets to the viral-fighting ability of stem cells uncovered (Todd Dubnicoff)
I’ve been writing about stem cells for many years and thought I knew most of the basic info about these amazing cells. But up until this week, I had no idea that stem cells are known to fight off viral infections much better than other cells. It does makes sense though. Stem cells give rise to and help maintain all the organs and tissues of the body. So, it would be bad news if, let’s say, a muscle stem cell multiplied to repair damaged tissue while carrying a dangerous virus.
How exactly stem cells fend off attacking viruses is a question that has eluded researchers for decades. But this week, results published in Cell by Rockefeller University scientists may provide an answer.
Stem cells lacking their protective genes are susceptible to infection by the dengue virus, in red. (Rockefeller University)
The researchers found that liver cells and stem cells defend themselves against viruses differently. In the presence of a virus, liver cells and most other cells react by releasing large amounts of interferon, a protein that acts as a distress signal to other cells in the vicinity. That signal activates hundreds of genes responsible for attracting protective immune cells to the site of infection.
Stem cells, however, are always in this state of emergency. Even in the absence of interferon, the antiviral genes were activated in stem cells. And when the stem cells were genetically engineering to lack some of the antiviral genes, the cells no longer could stop viral infection.
In a press release, senior author Charles Rice explained the importance of this work:
“By understanding more about this biology in stem cells, we may learn more about antiviral mechanisms in general.”
CIRM-funded clinical trial for ALS now available next door – in Canada (Kevin McCormack)
In kindergarten we are taught that it’s good to share. So, we are delighted that a Phase 3 clinical trial for ALS – also known as Lou Gehrig’s disease – that CIRM is helping fund is now expanding its reach across the border from the U.S. into Canada.
Brainstorm Cell Therapeutics, the company behind the therapy, says it is going to open a clinical trial site in Canada because so many Canadians have asked for it.
The therapy, as we described in a recent blog post, takes mesenchymal stem cells from the patient’s own bone marrow. Those cells are then modified in the lab to be able to churn out specific proteins that can help protect the brain cells attacked by ALS. The cells are then transplanted back into the patient and the hope is they will slow down, maybe even stop the progression of the disease.
Earlier studies showed the therapy was safe and seemed to benefit some patients. Now people with ALS across our northern border will get a chance to see if it really works.
Chaim Lebovits, the president and chief executive officer of BrainStorm, said in a press release:
“Although there are thousands of patients worldwide with ALS, we initially designed the Phase 3 trial to enroll U.S.-based patients only, primarily to make it easier for patient follow-up visits at the six U.S. clinical sites. However, due to an outpouring of inquiry and support from Canadian patients wanting to enroll in the trial, we filed an amendment with the FDA [the U.S. Food and Drug Administration] to allow Canada-based ALS patients to participate.”
Ask people what they know about geckos and the odds are they’ll tell you geckos have English accents and sell car insurance. Which tells you a lot more about the power of advertising than it does about the level of knowledge about lizards. Which is a shame, because the gecko has some amazing qualities, not the least of which is its ability to re-grow its tail. Now some researchers have discovered how it regenerates its tail, and what they’ve learned could one day help people with spinal cord injuries.
Geckos often detach a bit of their tail when being pursued by a predator, then grow a new one over the course of 30 days. Researchers at the University of Guelph in Canada found that the lizards use a combination of stem cells and proteins to do that.
They found that geckos have stem cells in their tail called radial glias. Normally these cells are dormant but that changes when the lizard loses its tail. As Matthew Vickaryous, lead author of the study, said in a news release:
“But when the tail comes off everything temporarily changes. The cells make different proteins and begin proliferating more in response to the injury. Ultimately, they make a brand new spinal cord. Once the injury is healed and the spinal cord is restored, the cells return to a resting state.”
Vickaryous hopes that understanding how the gecko can repair what is essentially an injury to its spinal cord, we’ll be better able to develop ways to help people with the same kind of injury.
Zika virus uses Trojan Horse strategy to infect developing brain In April 2015, the World Health Organization declared that infection by Zika virus and its connection to severe birth defects was an international public health emergency. The main concern has been the virus’ link to microcephaly, a condition in which abnormal brain development causes a smaller than normal head size at birth. Microcephaly leads to number of problems in these infants including developmental delays, seizures, hearing loss and difficulty swallowing.
A false color micrograph shows microglia cells (green) infected by the Zika virus (blue). Image Muotri lab/UCSD
The UCSD researchers behind the study chose to focus on microglia cells. In a press release, team leader Alysson Muotri explained their rationale for targeting these cells:
“During embryogenesis — the early stages of prenatal development — cells called microglia form in the yolk sac and then disperse throughout the central nervous system (CNS) of the developing child. Considering the timing of [Zika] transmission, we hypothesized that microglia might be serving as a Trojan horse to transport the virus during invasion of the CNS.”
In the developing brain, microglia continually travel throughout the brain and clear away dead or infected cells. Smuggling itself aboard microglia would give Zika a devious way to slip through the body’s defenses and infect other brain cells. And that’s exactly what Dr. Muotri’s team found.
Using human induced pluripotent stem cells (iPSCs), they generated brain stem cells – the kind found in the developing brain – and in lab dish infected them with Zika virus. When iPSC-derived microglia were added to the infected neural stem cells, the microglia gobbled them up and destroyed them, just as they would do in the brain. But when those microglia were placed next to uninfected brain stem cells, the Zika virus was easily transmitted to those cells. Muotri summed up the results this way:
“Our findings show that the Zika virus can infect these early microglia, sneaking into the brain where they transmit the virus to other brain cells, resulting in the devastating neurological damage we see in some newborns.”
The team went on to show that an FDA-approved drug to treat hepatitis – a liver disease often caused by viral infection – was effective at decreasing the infection of brain stem cells by Zika-carrying microglia. Since these studies were done in petri dishes, more research will be required to confirm that the microglia are a true drug target for stopping the devastating impact of Zika on newborns.
How stem cell research gives patients hope (Karen Ring). You can learn about the latest stem cell research for a given disease in seconds with a quick google search. You’ll find countless publications, news releases and blogs detailing the latest advancements that are bringing scientists and clinicians closer to understanding why diseases happen and how to treat or cure them.
But one thing these forms of communications lack is the personal aspect. A typical science article explains the research behind the study at the beginning and ends with a concluding statement usually saying how the research could one day lead to a treatment for X disease. It’s interesting, but not always the most inspirational way to learn about science when the formula doesn’t change.
However, I’ve started to notice that more and more, institutes and organizations are creating videos that feature the scientists/doctors that are developing these treatments AND the patients that the treatments could one day help. This is an excellent way to communicate with the public! When you watch and listen to a patient talk about their struggles with their disease and how there aren’t effective treatments at the moment, it becomes clear why funding and advancing research is important.
We have a great example of a patient-focused stem cell video to share with you today thanks to our friends at Americans for Cures, a non-profit organization that advocates for stem cell research. They posted a new video this week in honor of Stem Cell Awareness Day featuring patients and patient advocates responding to the question, “What does stem cell research give you hope for?”. Many of these patients and advocates are CIRM Stem Cell Champions that we’ve featured on our website, blog, and YouTube channel.
Americans for Cures is encouraging viewers to take their own stab at answering this important question by sharing a short message (on their website) or recording a video that they will share with the stem cell community. We hope that you are up for the challenge!
Mini-brains help uncover some of Zika’s secrets (Kevin McCormack). One of the hardest things about trying to understand how a virus like Zika can damage the brain is that it’s hard to see what’s going on inside a living brain. That’s not surprising. It’s not considered polite to do an autopsy of someone’s brain while they are still using it.
Microscopic image of a mini brain organoid, showing layered neural tissue and different groups of neural stem cells (in blue, red and magenta) giving rise to neurons (green). Image: Novitch laboratory/UCLA
But now researchers at UCLA have come up with a way to mimic human brains, and that is enabling them to better understand how Zika inflicts damage on a developing fetus.
For years researchers have been using stem cells to help create “mini brain organoids”, essentially clusters of some of the cells found in the brain. They were helpful in studying some aspects of brain behavior but limited because they were very small and didn’t reflect the layered complexity of the brain.
In a study, published in the journal Cell Reports, UCLA researchers showed how they developed a new method of creating mini-brain organoids that better reflected a real brain. For example, the organoids had many of the cells found in the human cortex, the part of the brain that controls thought, speech and decision making. They also found that the different cells could communicate with each other, the way they do in a real brain.
They used these organoids to see how the Zika virus attacks the brain, damaging cells during the earliest stages of brain development.
In a news release, Momoko Watanabe, the study’s first author, says these new organoids can open up a whole new way of looking at the brain:
“While our organoids are in no way close to being fully functional human brains, they mimic the human brain structure much more consistently than other models. Other scientists can use our methods to improve brain research because the data will be more accurate and consistent from experiment to experiment and more comparable to the real human brain.”
iPSC recipes go head-to-head: which one is best? In the ten years since the induced pluripotent stem cell (iPSC) technique was first reported, many different protocols, or recipes, for reprogramming adult cells, like skin, into iPSCs have been developed. These variations bring up the question of which reprogramming recipe is best. This question isn’t the easiest to answer given the many variables that one needs to test. Due to the cost and complexity of the methods, comparisons of iPSCs generated in different labs are often performed. But one analysis found significant lab-to-lab variability which can really muck up the ability to make a fair comparison.
A Stanford University research team, led by Dr. Joseph Wu, sought to eliminate these confounding variables so that any differences found could be attributed specifically to the recipe. So, they tested six different reprogramming methods in the same lab, using cells from the same female donor. And in turn, these cells were compared to a female source of embryonic stem cells, the gold standard of pluripotent stem cells. They reported their findings this week in Nature Biomedical Engineering.
Previous studies had hinted that the reprogramming protocol could affect the ability to fully specialize iPSCs into a particular cell type. But based on their comparisons, the protocol chosen did not have a significant impact on how well iPSCs can be matured. Differences in gene activity are a key way that researchers do side-by-side comparisons of iPSCs and embryonic stem cells. And based on the results in this study, the reprogramming method itself can influence the differences. A gene activity comparison of all the iPSCs with the embryonic stem cells found the polycomb repressive complex – a set of genes that play an important role in embryonic development and are implicated in cancer – had the biggest difference.
In a “Behind the Paper” report to the journal, first author Jared Churko, says that based on these findings, their lab now mostly uses one reprogramming protocol – which uses the Sendai virus to deliver the reprogramming genes to the cells:
“The majority of our hiPSC lines are now generated using Sendai virus. This is due to the ease in generating hiPSCs using this method as well as the little to no chance of transgene integration [a case in which a reprogramming gene inserts into the cells’ DNA which could lead to cancerous growth].”
Still, he adds a caveat that the virus does tend to linger in the cells which suggests that:
“cell source or reprogramming method utilized, each hiPSC line still requires robust characterization prior to them being used for downstream experimentation or clinical use.”