CIRM invests $1.3 million to study stem cells in metabolic liver disease

Grikscheit

Dr. Tracy Grikscheit. Image courtesy of Children’s Hospital LA.

Metabolic liver disease, is an emerging public health concern in Western countries, but has largely been overshadowed by health issues such as cancer and diabetes. Chronic liver disease (of which metabolic liver disease is a significant contributor) however, is a significant public health concern, evidenced by its contribution to nearly 2 million deaths per year worldwide.

The primary treatment option for metabolic liver disease is a liver transplant. In fact, of the liver transplants performed every year, 14% are due to damage associated with metabolic disorders. With any organ transplant, however, such a procedure comes with drawbacks, the most frustrating of which is the need for patients to wait for an organ donor.

As transplants are not a reasonable or feasible option for many people, alternative treatment options are necessary.  Enter Dr. Tracy Grikscheit, a doctor-scientist at the Children’s Hospital Los Angeles, who hopes to make liver transplant a thing of the past for the millions of people who live with metabolic liver disease.

Dr. Grikscheit was awarded a $1.3 million grant to study how stem cells can be used to treat liver disease caused by metabolic disorders. In a press release, Dr. Grikscheit details the importance and practicality of using stem cells to treat liver disease:

“Liver-based metabolic diseases are the perfect starting point to apply cellular therapy to liver disorders. The only current therapy — a liver transplant — is costly and in short supply. Plus, it requires suppressing the patient’s immune system, which has long-term consequences.”

The project, termed UPLiFT for Universal Pluripotent Stem Cell Therapy, aims to use pluripotent stem cells (cells that can turn into any cell in the body) to correct liver associated disorders like Crigler-Najjar Syndrome. A genetic mutation in liver cells of these patients makes them unable to covert bilirubin (a byproduct of red blood cell degradation) to its non-toxic form. Dr. Grikscheit hopes to bypass the need for a liver transplant by giving these patients pluripotent stem cells that can become liver cells without the genetic mutation, and are able to convert bilirubin to its non-toxic form. The use of pluripotent stem cells would also potentially eliminate the need for lifelong immunosuppressive therapy

Dr. Grikscheit will use the CIRM grant to test safety and efficacy of the stem cell treatment in pre-clinical trials to determine the optimal cell dosage that will be both safe and relieve disease symptoms, as well as assessing any off-target effects of the treatment. She has previously received a grant from CIRM to study stem cell therapy options for digestive neuromuscular condition, which you can read about here.

 

Stories that caught our eye: SanBio’s Traumatic Brain Injury trial hits its target; A new approach to endometriosis; and a SCID kid celebrates Halloween in style

TBI

Traumatic brain injury: graphic courtesy Brainline.org

Hopeful signs for treating brain injuries

There are more than 200,000 cases of traumatic brain injury (TBI) in the US every year. The injuries can be devastating, resulting in everything from difficult sleeping to memory loss, depression and severe disability. There is no cure. But this week the SanBio Group had some encouraging news from its Phase 2 STEMTRA clinical trial.

In the trial patients with TBI were given stem cells, derived from the bone marrow of healthy adult donors. When transplanted into the area of injury in the brain, these cells appear to promote recovery by stimulating the brain’s own regenerative ability.

In this trial the cells demonstrated what the company describes as “a statistically significant improvement in their motor function compared to the control group.”

CIRM did not fund this research but we are partnering with SanBio on another clinical trial targeting stroke.

 

Using a woman’s own cells to heal endometriosis

Endometriosis is an often painful condition that is caused when the cells that normally line the inside of the uterus grow outside of it, causing scarring and damaging other tissues. Over time it can result in severe pain, infertility and increase a woman’s risk for ovarian cancer.

There is no effective long-term treatment but now researchers at Northwestern Medicine have developed an approach, using the woman’s own cells, that could help treat the problem.

The researchers took cells from women, turned them into iPS pluripotent stem cells and then converted those into healthy uterine cells. In laboratory tests these cells responded to the progesterone, the hormone that plays a critical role in the uterus.

In a news release, Dr. Serdar Bulun, a senior author of the study, says this opens the way to testing these cells in women:

“This is huge. We’ve opened the door to treating endometriosis. These women with endometriosis start suffering from the disease at a very early age, so we end up seeing young high school girls getting addicted to opioids, which totally destroys their academic potential and social lives.”

The study is published in the journal Stem Cell Reports.

IMG_20181031_185752

Happy Halloween from a scary SCID kid

A lot of the research we write about on the Stem Cellar focuses on potential treatments or new approaches that show promise. So every once in a while, it’s good to remind ourselves that there are already stem cell treatments that are not just showing promise, they are saving lives.

That is the case with Ja’Ceon Golden. Regular readers of our blog know that Ja’Ceon was diagnosed with Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease” when he was just a few months old. Children born with SCID often die in the first few years of life because they don’t have a functioning immune system and so even a simple infection can prove life-threatening.

Fortunately Ja’Ceon was enrolled in a CIRM-funded clinical trial at UC San Francisco where his own blood stem cells were genetically modified to correct the problem.

IMG_20181030_123500

Today he is a healthy, happy, thriving young boy. These pictures, taken by his great aunt Dannie Hawkins, including one of him in his Halloween costume, show how quickly he is growing. And all thanks to some amazing researchers, an aunt who wouldn’t give up on him, and the support of CIRM.

Mechanical forces are the key to speedy recovery after blood cancer treatment

MIT-Stem-Cell-Mechanics_0

Mesenchymal stem cells grown on a surface with specialized mechanical properties. Image courtesy of Krystyn Van Vliet at MIT.

Blood cancers, such as leukemia and lymphoma, are projected to be responsible for 10% of all new cancer diagnoses this year. These types of cancers are often treated by killing the patient’s bone marrow (the site of blood cell manufacturing), with a treatment called irradiation. While effective for ridding the body of cancerous cells, this treatment also kills healthy blood cells. Therefore, for a time after the treatment, patients are particularly vulnerable to infections, because the cellular components of the immune system are down for the count.

Now scientists at MIT have devised a method to make blood cells regenerate faster and  minimize the window for opportunistic infections.

Using multipotent stem cells (stem cells that are able to become multiple cell types) grown on a new and specialized surface that mimics bone marrow, the investigators changed the stem cells into different types of blood cells. When transplanted into mice that had undergone irradiation, they found that the mice recovered much more quickly compared to mice given stem cells grown on a more traditional plastic surface that does not resemble bone marrow as well.

This finding, published in the journal Stem Cell Research and Therapy, is particularly revolutionary, because it is the first time researchers have observed that mechanical properties can affect how the cells differentiate and behave.

The lead author of the study attributes the decreased recovery time to the type of stem cell that was given to mice compared to what humans are normally given after irradiation. Humans are given a stem cell that is only able to become different types of blood cells. The mice in this study, however, were give a stem cell that can become many different types of cells such as muscle, bone and cartilage, suggesting that these cells somehow changed the bone marrow environment to promote a more efficient recovery. They attributed a large part of this phenomenon to a secreted protein call ostepontin, which has previously been describe in activating the cells of the immune system.

In a press release, Dr. Viola Vogel, a scientist not related to study, puts the significance of these findings in a larger context:

“Illustrating how mechanopriming of mesenchymal stem cells can be exploited to improve on hematopoietic recovery is of huge medical significance. It also sheds light onto how to utilize their approach to perhaps take advantage of other cell subpopulations for therapeutic applications in the future.”

Dr. Krystyn Van Vliet, explains the potential to expand these findings beyond the scope of just blood cancer treatment:

“You could imagine that by changing their culture environment, including their mechanical environment, MSCs could be used for administration to target several other diseases such as Parkinson’s disease, rheumatoid arthritis, and others.”

 

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

HIV AIDS

While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

Jeff Sheehy

CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

Children’s Hospital of Los Angeles $1,297,512

 

DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

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Congresswoman Barbara Lee (D-CA 13th District)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

$93 million

$30 million

TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K

 

 

Sequencing data helps us understand the genes involved in heart cell development

skin cells to beating heart

Human heart cells generated in the laboratory. Image courtesy of Nathan Palapant at the University of Queensland

Heart disease is the leading cause of death for both men and women in the United States and is estimated to be responsible for 31% of all deaths globally. This disease encompasses a wide variety of conditions that all effect how well your heart is able to pump blood to the rest of your body. One of the reasons that heart disease is so devastating is because, unlike many other organs in our bodies, heart tissue is not able to repair itself once it is damaged. Now scientists at the Institute for Molecular Bioscience at the University of Queensland and the Garvan Institute for Medical Research in Australia have conducted a tour de force study to exquisitely understand the genes involved in heart development.

The findings of the study are published in the journal Cell Stem Cell. in a press release, Dr. Nathan Palapant, one of the the lead authors, says this type of research could pay dividends for heart disease treatment because:

“We think the answers to heart repair almost certainly lie in understanding heart development. If we can get to grips with the complex choreography of how the heart builds itself in the first place, we’re well placed to find new approaches to helping it rebuild after damage.”

To determine which genes are involved in heart cell development, the investigators use a method called single cell RNA sequencing. This technique allowed them to measure how 17,000 genes (almost every gene that is active in the heart) were being turned on and off during various stages of heart cell development in 40,000 human pluripotent stem cells (stem cells that are capable of becoming any other cell type) experimentally induced to turn into heart cells.  This data set, the first of its kind, is a critical new resource for all scientists studying heart development and disease.

Interestingly, this study also addressed a commonly present, but rarely discussed issue with scientific studies: how applicable are results generated in vitro (in the lab) rather than the body, in the context of human health and disease? It is well known that heart cells generated in the lab do not have the exact same characteristics as mature heart cells found in our bodies, but the extent and precise nature of those discrepancies is not well understood. These scientists find that a gene called HOPX, which is one of earliest markers of heart cell development, is not always expressed when it should be during in vitro cardiac cell development, which, in turn, affects expression of other genes that are downstream of HOPX later on in development. Therefore, these scientists suggest that mis-expression of HOPX  might be one reason why in vitro heart cells express different genes and are distinct from heart cells in humans.

The scientists also learned that HOPX is responsible for controlling whether the developing heart cell moves past the “immature” dividing phase to the mature phase where cells grow bigger, but do not divide. This finding shows that this data set is powerful both for determining differences between laboratory grown cells versus mature human cells, but also provides critical biological information about heart cell development.

Joseph Powell, another lead author of this research, further explains how this work contributes to the important fundamentals of heart cell development:

“Each cell goes through its own series of complex, nuanced changes. They are all different, and changes in one cell affect the activity of other cells. By tracking those changes across the different stages of development, we can learn a huge amount about how different sub-types of heart cells are controlled, and how they work together to build the heart.”

Hits and Myths as people celebrate Stem Cell Awareness Day

UC Davis #1

Stem Cell Awareness Day at UC Davis

Every year, the second Wednesday in October is set aside as Stem Cell Awareness Day, a time to celebrate the progress being made in the field and to remind us of the challenges that lie ahead.

While the event began here in California in 2008, with then-Governor Arnold Schwarzenegger highlighting the work of CIRM, saying: ”The discoveries being made today in our Golden State will have a great impact on many around the world for generations to come.” It has since grown to become a global event.

Here in California, for example, UC Davis and the University of Southern California (USC) both held events to mark the day.

At UC Davis Jan Nolta, PhD., the Director of the Stem Cell Program, introduced a series of speakers who highlighted the terrific work being done at the university. Peter Belafsky talked about using stem cells to repair damaged trachea and to help people who are experiencing voice or swallowing disorders. Mark Lee highlighted the progress being made in using stem cells to repair hard-to-heal broken bones. Aijun Wang focused on some really exciting work that could one day lead to a therapy for spina bifida (including some ridiculously cute video of English bulldogs who are able to walk again because of this therapy.)

USC hosted 100 local high school students for a panel presentation and discussion about careers in stem cell research. The panel featured four scientists talking about their experience, why the students should think about a career in science and how to go about planning one. USC put together a terrific video of the researchers talking about their experiences, something that can help any student around the US consider becoming part of the future of stem cell research.

Similar events were held in other institutions around California. But the celebration wasn’t limited to the Golden State. At the Texas Heart Institute in Houston, Texas, they held an event to talk to the public about the clinical trials they are supporting using stem cells to help people suffering from heart failure or other heart-related issues.

RegMedNet

Finally, the UK-based RegMedNet, a community site that unites the diverse regenerative medicine community, marked the day by exploring some of the myths and misconceptions still surrounding stem cells and stem cell research.

You can read those here.

Every group takes a different approach to celebrating Stem Cell Awareness Day, but each is united by a common desire, to help people understand the progress being made in finding new treatments and even cures for people with unmet medical needs.

Why having a wrinkled brain is a good thing

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We normally associate wrinkles with aging, such as wrinkled skin. But there’s one organ that is wrinkled right from the time we are born. It’s our brain. And new research shows those wrinkles are not a sign of age but are, in fact, a sign of just how large and complex our brains are.

The wrinkles, according to U.C. Santa Barbara (UCSB) postdoctoral scholar Eyal Karzbrun, are vital to our development because they create a greater surface area giving our neurons, or brain nerve cells, more space to create connections and deliver information.

In an article in UCSB’s Daily Nexus, Karzbrun says while our knowledge of the brain is increasing there are still many things we don’t understand:

“The brain is a complex organ whose organization is essential to its function. Yet it is ‘assembled by itself’. How this assembly takes place and what physics come into play is fundamental to our understanding of the brain.”

Eyal Karzbrun

Eyal Karzbrun: Photo courtesy UCSB

Karzbrun used stem cells to create 3D clusters of brain cells, to better understand how they organize themselves. He said brains are like computers in the way they rely on surface area to process information.

“In order to be computationally strong and quick, what your brain does is take a lot of surface area and put it in a small volume. The cerebral cortex, which occupies most of the volume in your brain, has a unique architecture in which neurons are layered on the outer surface of the brain, and the bulk of the brain is composed of axons, [or] biological wire which interconnect the neurons.”

Karzbrun says gaining a deeper understanding of how the brain is formed, and why it takes the shape it does, may help us develop new approaches to treating problems in the brain.

 

Research Targeting Prostate Cancer Gets Almost $4 Million Support from CIRM

Prostate cancer

A program hoping to supercharge a patient’s own immune system cells to attack and kill a treatment resistant form of prostate cancer was today awarded $3.99 million by the governing Board of the California Institute for Regenerative Medicine (CIRM)

In the U.S., prostate cancer is the second most common cause of cancer deaths in men.  An estimated 170,000 new cases are diagnosed each year and over 29,000 deaths are estimated in 2018.  Early stage prostate cancer is usually managed by surgery, radiation and/or hormone therapy. However, for men diagnosed with castrate-resistant metastatic prostate cancer (CRPC) these treatments often fail to work and the disease eventually proves fatal.

Poseida Therapeutics will be funded by CIRM to develop genetically engineered chimeric antigen receptor T cells (CAR-T) to treat metastatic CRPC. In cancer, there is a breakdown in the natural ability of immune T-cells to survey the body and recognize, bind to and kill cancerous cells. Poseida is engineering T cells and T memory stem cells to express a chimeric antigen receptor that arms these cells to more efficiently target, bind to and destroy the cancer cell. Millions of these cells are then grown in the laboratory and then re-infused into the patient. The CAR-T memory stem cells have the potential to persist long-term and kill residual cancer calls.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer. CIRM is pleased to partner on this program and to add it to its portfolio that involves CAR T memory stem cells.”

Poseida Therapeutics plans to use the funding to complete the late-stage testing needed to apply to the Food and Drug Administration for the go-ahead to start a clinical trial in people.

Quest Awards

The CIRM Board also voted to approve investing $10 million for eight projects under its Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Among those approved for funding are:

  • Eric Adler at UC San Diego is using genetically modified blood stem cells to treat Danon Disease, a rare and fatal condition that affects the heart
  • Li Gan at the Gladstone Institutes will use induced pluripotent stem cells to develop a therapy for a familial form of dementia
  • Saul Priceman at City of Hope will use CAR-T therapy to develop a treatment for recurrent ovarian cancer

Because the amount of funding for the recommended applications exceeded the money set aside, the Application Subcommittee voted to approve partial funding for two projects, DISC2-11192 and DISC2-11109 and to recommend, at the next full Board meeting in October, that the projects get the remainder of the funds needed to complete their research.

The successful applications are:

 

APPLICATION

 

TITLE

 

INSTITUTION

CIRM COMMITTED FUNDING
DISC2-11131 Genetically Modified Hematopoietic Stem Cells for the

Treatment of Danon Disease

 

 

U.C San Diego

 

$1,393,200

 

DISC2-11157 Preclinical Development of An HSC-Engineered Off-

The-Shelf iNKT Cell Therapy for Cancer

 

 

U.C. Los Angeles

 

$1,404,000

DISC2-11036 Non-viral reprogramming of the endogenous TCRα

locus to direct stem memory T cells against shared

neoantigens in malignant gliomas

 

 

U.C. San Francisco

 

$900,000

DISC2-11175 Therapeutic immune tolerant human islet-like

organoids (HILOs) for Type 1 Diabetes

 

 

Salk Institute

 

$1,637,209

DISC2-11107 Chimeric Antigen Receptor-Engineered Stem/Memory

T Cells for the Treatment of Recurrent Ovarian Cancer

 

 

City of Hope

 

$1,381,104

DISC2-11165 Develop iPSC-derived microglia to treat progranulin-

deficient Frontotemporal Dementia

 

 

Gladstone Institutes

 

$1,553,923

DISC2-11192 Mesenchymal stem cell extracellular vesicles as

therapy for pulmonary fibrosis

 

 

U.C. San Diego

 

$865,282

DISC2-11109 Regenerative Thymic Tissues as Curative Cell

Therapy for Patients with 22q11 Deletion Syndrome

 

 

Stanford University

 

$865,282

 

 

Headline: Stem Cell Roundup: Here are some stem cell stories that caught our eye this past week.

In search of a miracle

Jordan and mother

Luane Beck holds Jordan in the emergency room while he suffers a prolonged seizure. Jordan’s seizures sometimes occur one after another with no break, and they can be deadly without emergency care. Photo courtesy San Francisco Chronicle’s Kim Clark

One of the toughest parts of my job is getting daily calls and emails from people desperate for a stem cell treatment or cure for themselves or a loved one and having to tell them that I don’t know of any. You can hear in their voice, read it in their emails, how hard it is for them to see someone they love in pain or distress and not be able to help them.

I know that many of those people may think about turning to one of the many stem cell clinics, here in the US and in Mexico and other countries, that are offering unproven and unapproved therapies. These clinics are offering desperate people a sense of hope, even if there is no evidence that the therapies they provide are either safe or effective.

And these “therapies” come with a big cost, both emotional and financial.

The San Francisco Chronicle this week launched the first in a series of stories they are doing about stem cells and stem cell research, the progress being made and the problems the field still faces.

One of the biggest problems, are clinics that offer hope, at a steep price, but no evidence to show that hope is justified. The first piece in the Chronicle series is a powerful, heart breaking story of one mother’s love for her son and her determination to do all she can to help him, and the difficult, almost impossible choices she has to make along the way.

It’s called: In search of a miracle.

A little turbulence, and a French press-like device, can help boost blood platelet production

Every year more than 21 million units of blood are transfused into people in the US. It’s a simple, life-saving procedure. One of the most important elements in transfusions are  platelets, the cells that stop bleeding and have other healing properties. Platelets, however, have a very short shelf life and so there is a constant need to get more from donors. Now a new study from Japan may help fix that problem.

Platelets are small cells that break off much larger cells called megakaryocytes. Scientists at the Center for iPS Cell Research and Application (CiRA) created billions of megakaryocytes using iPS technology (which turns ordinary cells into any other kind of cell in the body) and then placed them in a bioreactor. The bioreactor then pushed the cells up and down – much like you push down on a French press coffee maker – which helped promote the generation of platelets.

In their study, published in the journal Cell, they report they were able to generate 100 billion platelets, enough to be able to treat patients.

In a news release, CiRA Professor Koji Eto said they have shown this works in mice and now they want to see if it also works in people:

“Our goal is to produce platelets in the lab to replace human donors.”

Stem Cell Photo of the Week 

Photo Jul 11, 6 00 19 PM

Students at the CIRM Bridges program practice their “elevator pitch”. Photo Kyle Chesser

This week we held our annual CIRM Bridges to Stem Cell Research conference in Newport Beach. The Bridges program provides paid internships for undergraduate and masters-level students, a chance to work in a world-class stem cell research facility and get the experience needed to pursue a career in science. The program is training the next generation of stem cell scientists to fill jobs in California’s growing stem cell research sector.

This year we got the students to practice an “elevator Pitch”, a 30 second explanation, in plain English, of what they do, why they do it and why people should care. It’s a fun exercise but also an important one. We want scientists to be able to explain to the public what they are doing and why it’s important. After all, the people of California are supporting this work so they have a right to know, in language they can understand, how their money is changing the face of medicine.

Starving stem cells of oxygen can help build stronger bones

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J. Kent Leach: Photo courtesy UC Davis

We usually think that starving something of oxygen is going to make it weaker and maybe even kill it. But a new study by J. Kent Leach at UC Davis shows that instead of weakening bone defects, depriving them of oxygen might help boost their ability to create new bone or repair existing bone.

Leach says in the past the use of stem cells to repair damaged or defective bone had limited success because the stem cells often didn’t engraft in the bone or survive long if they did. That was because the cells were being placed in an environment that lacked oxygen (concentration levels in bone range from 3% to 8%) so the cells found it hard to survive.

However, studies in the lab had shown that if you preconditioned mesenchymal stem cells (MSCs), by exposing them to low oxygen levels before you placed them on the injury site, you helped prolong their viability. That was further enhanced by forming the MSCs into three dimensional clumps called spheroids.

Lightbulb goes off

In the  current study, published in Stem Cells, Leach says the earlier spheroid results  gave him an idea:

“We hypothesized that preconditioning MSCs in hypoxic (low oxygen) culture before spheroid formation would increase cell viability, proangiogenic potential (ability to create new blood vessels), and resultant bone repair compared with that of individual MSCs.”

So, the researchers placed one group of human MSCs, taken from bone marrow, in a dish with just 1% oxygen, and another identical group of MSCs in a dish with normal oxygen levels. After three days both groups were formed into spheroids and placed in an alginate hydrogel, a biopolymer derived from brown seaweed that is often used to build cellular cultures.

Seaweed

Brown seaweed

The team found that the oxygen-starved cells lasted longer than the ones left in normal oxygen, and the longer those cells were deprived of oxygen the better they did.

Theory is great, how does it work in practice?

Next was to see how those two groups did in actually repairing bones in rats. Leach says the results were encouraging:

“Once again, the oxygen-deprived, spheroid-containing gels induced significantly more bone healing than did gels containing either preconditioned individual MSCs or acellular gels.”

The team say this shows the use of these oxygen-starved cells could be an effective approach to repairing hard-to-heal bone injuries in people.

“Short‐term exposure to low oxygen primes MSCs for survival and initiates angiogenesis (the development of new blood vessels). Furthermore, these pathways are sustained through cell‐cell signaling following spheroid formation. Hypoxic (low oxygen) preconditioning of MSCs, in synergy with transplantation of cells as spheroids, should be considered for cell‐based therapies to promote cell survival, angiogenesis, and bone formation.”

CIRM & Dr. Leach

While CIRM did not fund this study we have invested more than $1.8 million in another study Dr. Leach is doing to develop a new kind of imaging technology that will help us see more clearly what is happening in bone and cartilage-targeted therapies.

In addition, back in March of 2012, Dr. Leach spoke to the CIRM Board about his work developing new approaches to growing bone.