New Video: Spinal Cord Injury and a CIRM-Funded Stem Cell-Based Trial

Just 31 years old, Richard Lajara thought he was going to die.


Richard Lajara, the 4th participant in Geron’s stem cell-based clinical trial for spinal cord injury.

On September 9, 2011 he slipped on some rocks at a popular swimming hole and was swept down a waterfall headfirst into a shallow, rocky pool of water. Though he survived, the fall left him paralyzed from the waist down due to a severed spinal cord.

Patient Number Four
At that same time period, Geron Inc. had launched a clinical trial CIRM helped fund testing the safety of a stem cell-based therapy for spinal cord injury (SCI). It was the world’s first trial using cells derived from human embryonic stem cells and Lajara was an eligible candidate. Speaking to CIRM’s governing Board this past summer for a Spotlight on Disease seminar, he recalled his decision to participate:

“When I participated with the Geron study, I was honored to be a part of it. It was groundbreaking and the decision was pretty easy. I understood that it was very early on and I wasn’t looking for any improvement but laying the foundation [for future trials].”

A few months after his treatment, Geron discontinued the trial for business reasons. Lajara was devastated and felt let down. But this year the therapy got back on track with the announcement in June by Asterias Biotherapeutics that they had treated their first spinal cord injury patient after having purchased the stem cell assets of Geron.

Getting Hope Back on Track
Dr. Jane Lebkowski, Asterias’ President of R&D and Chief Scientific Officer, also spoke at the Spotlight on Disease seminar to provide an overview and update on the company’s clinical trial. A video recording of Lebkowski’s and Lajara’s presentations is now available on our web site and posted here:

As Dr. Lebkowski explains in the video, Asterias didn’t have to start from scratch. The Geron study data showed the therapy was well tolerated and didn’t cause any severe safety issues. In that trial, five people (including Richard Lajara) with injuries in their back received an injection of two million stem cell-derived oligodendrocyte progenitor cells into the site of spinal cord damage. The two million-cell dose was not expected to show any effect but was focused on ensuring the therapy was safe.

Oligodendrocyte Precursors: Spinal Cord Healers
As the former Chief Scientific Officer at Geron, Lebkowski spoke first hand about why the oligodendrocyte precursor was the cell of choice for the clinical trial. Previous animal studies showed that oligodendrocyte progenitors, a cell type normally found in the spinal cord, have several properties that make them ideal cells for treating SCI: first, they help stimulate the growth of damaged neurons, the cell type responsible for transmitting electrical signals from the brain to the limbs.

Second, the oligodendrocytes produce myelin, a protein that acts as an insulator of neurons, very much like the plastic covering on a wire. In many spinal cord injuries, the nerves are still intact but lose their myelin insulation and their ability to send signals. Third, the oligodendrocytes release other proteins that help reduce the size of cysts that often form at the injury site and damage neurons. In preclinical experiments, these properties of oligodendrocyte progenitors improved limb movement in spinal cord-severed rodents.

Together, the preclinical animal studies and the safety data from the Geron clinical trial helped Asterias win approval from the Food and Drug Administration (FDA) to start their current trial, also funded by CIRM, this time treating patients with neck injuries instead of back injuries.

The Asterias trial is a dose escalation study with the first group of three patients again receiving two million cells. The trial was designed such that if this dose shows a good safety profile in the neck, as it did in the Geron trial in the back, then the next cohort of five patients will receive 10 million cells. In fact, Asterias reported in August that the lower dose was not only safe but also showed some encouraging results in one of the patients. And just two days ago Asterias announced their data monitoring committee recommended to begin enrolling patients for the 10 million cell dose.  If all continues to go well with safety, the dose will be escalated to 20 million cells in the third cohort of five patients. While two million cells was a very low safety dose, Asterias anticipates seeing some benefit from the 10 and 20 million cell doses.

Changing Lives by Increasing Independence
Does Lebkowski’s team expect the patients to stand up out of their wheelchairs post-treatment? No, but they do hope to see a level of improvement that could dramatically increase quality of life and decrease the level of care needed. Specifically, they are looking to see a so-called “two motor level improvement.” In her talk Lebkowski explained this quantitative measure with the chart below:

“If a patient is a C4 [meaning their abilities are consistent with someone with a spinal cord injury at the fourth cervical, or neck, bone] they will need anywhere from 18 to 24 hours of attendant care for daily living. If we could improve their motor activity such that they become a C6, that is just two motor levels, what you can see is independence tremendously increases and we go from 18 to 24 hour attendant care to having attendant care for about four hours of housework.”

Slide13 cropped

Small improvements in movement abilities can be life changing for people with spinal cord injuries.

It’s so exciting the field is at a point in time that scientists like Dr. Lebkowski are discussing real stem cell-based clinical trials that are underway in real patients who could achieve real improvements in their lives that otherwise would not be possible.

And we have people like Richard Lajara to thank. I think Dr. Oswald Stewart, the Board’s spinal cord injury patient advocate, summed it up well when speaking to Lajara at the meeting:

“Science and discovery and translation [into therapies] doesn’t happen without people like you who are willing to put yourselves on the line to move things forward. Thank you for being in that first round of people testing this new therapy.”

The New World That iPS Cells Will Bring

A stem cell champion was crowned last month. Dr. Takahashi from the RIKEN center in Japan received the prestigious Ogawa-Yamanaka Prize for developing a human iPS cell therapy to treat a debilitating eye disease called macular degeneration. We wrote about the event held at the Gladstone Institutes in a previous blog and saved the juicy insights from Dr. Takahashi’s scientific presentation and her CIRM-exclusive interview for today.  We also put together a two minute video (see below) based on the interview with her as well as with Dr. Deepak Srivastava, Director of the Gladstone Institute of Cardiovascular Disease and Mr. Hiro Ogawa, a co-founder of the Ogawa-Yamanaka Prize.

Dawn of iPS Cells

As part of the ceremony, Dr. Takahashi gave a scientific talk on the “new world that iPS cells will bring”. She began with a historical overview of stem cell research, starting with embryonic stem cells and the immune rejection and ethical issues associated with their use. She then discussed Dr. Yamanaka’s game-changing discovery of iPS cells, which offered new strategies for disease modeling and potential treatments that avoid some of the issues can complicate embryonic stem cells.

Her excitement over this discovery was palpable as she explained how she immediately jumped into the iPS cell field and got her hands dirty. Knowing that this technology could have huge implications for regenerative medicine and the development of stem cell therapies, she made herself a seemingly unattainable promise. “I said to myself, I will apply iPS cells to humans within five years. And I became a woman of her words.”

An iPS cell world

Dr. Takahashi went on to tell her success story, and why she chose to develop an iPS cell therapy to treat a disease of blindess, age-related macular degeneration (AMD). She explained how AMD is a serious unmet medical need. The current treatment involves injections of an antibody that blocks the activity of a growth factor called VEGF. This factor causes an overgrowth of blood vessels in the eye, which does major damage to the cells in the retina and can cause blindness. This therapy however, is only useful for some forms of AMD not all.


Dr. Masayo Takahashi describing her team’s iPS-based therapy for macular degeneration during the inaugural ceremony for the Ogawa-Yamanaka Prize at The Gladstone Institutes.

She believed she could fix this problem by developing an iPS cell technology that would replace lost cells in the eye in AMD patients. To a captivated crowd, she described how she was able to generate a sheet of human iPS derived cells called retinal pigment epithelial (RPE) cells from a patient with AMD. This sheet was transplanted into the eye of the patient in the first ever iPS cell clinical trial. The transplant was successful and the patient had no adverse effects to the treatment.

While the clinical trial is currently on hold, Dr. Takahashi explained that she and her team learned a lot from this experience. They are currently pursuing additional safety measures for their iPS cell technology to make sure that the stem cell transplants will not cause cancer or other bad outcomes in humans.

Autologous vs. Allogeneic?

Another main topic in her speech, was the choice between using autologous (iPS cells made from a patient and transplanted back into the same patient) and allogeneic (iPS cells made from a donor and then transplanted into a patient) iPS cells for transplantation in humans. Dr. Tahakashi’s opinion was that autologous would be ideal, but not scaleable due to high costs and the amount of time it would take to make iPS cell lines for individual patients.


iPS cells reprogrammed from a woman’s skin. Blue shows nuclei. Green and red indicate proteins found in reprogrammed cells but not in skin cells (credit: Kathrin Plath / UCLA).

Her solution is to use an arsenal of allogeneic iPS cells that can be transplanted into patients without rejection by the immune system. This may be possible if both the donor and the patient share the same combination (called a “haplotype”) of cell surface proteins on their immune cells called human leukocyte antigens (HLA). She highlighted the work ongoing in Japan to generate a stock of HLA haplotype matched iPS cell lines that could be used for most of the Japanese population.

 Changing the regulatory landscape in Japan

It was clear from her talk that her prize winning accomplishments didn’t happen without a lot of blood, sweat, and tears both at the bench and in the regulatory arena. In a CIRM exclusive interview, Dr. Takahashi further explained how her pioneering efforts to bring iPS cells to patients helped revolutionize the regulatory landscape in Japan to make it faster and easier to test iPS cells in the clinic.

The power of iPS cells changed the Japanese [regulatory] law dramatically. We made a new chapter for regenerative medicine in pharmaceutical law. With that law, the steps are very quick for cell therapy. In the new chapter [of the law] … conditional approval will be given if you prove the safety of the cell [therapy]. It’s very difficult to show the efficacy completely in a statistical manner for regenerative medicine. So the law says we don’t have to prove the efficacy [of the therapy] thoroughly with thousands of patients. Only a small number of patients are needed for the conditional approval. That’s the big difference.”

We were curious about Dr. Takahashi’s involvement in getting these regulatory changes to pass, and learned that she played a significant role on the academic side to convince the Japanese ministry to change the laws.

This law was made in the cooperation with the ministry and academia. That was one thing that had never happened before. Academia means mainly the Japanese society for the regenerative medicine, and I’m a committee member of that. So we talked about the ideal law for regenerative medicine, and our society suggested various points to the ministry. And to our surprise, the ministry accepted almost all of the points and included them into the law. That was wonderful. Usually we are very conservative and slow in changing, but this time, I was amazed how quickly the law has been changed. It’s the power of iPS cells.”

The iPS cell future is now

As a champion stem cell scientist and a leader in regenerative medicine, Dr. Takahashi took the opportunity at the end of the event to emphasize that all scientists and clinicians in the iPS cell therapy field need to consider three things: develop safe protocols for generating iPS cells that become standard practice, understand the patient’s needs by focusing on how to benefit patients the most, and think of iPS cells as a treatment and consider the risk when developing these therapies.

The new world of iPS cells is opening doors onto uncharted territory, but Dr. Takahashi’s wise words provide a solid roadmap for the future success of iPS cell therapies.

Seeing is believing: using video to explain stem cell science

People are visual creatures. So it’s no surprise that many of us learn best through visual means. In fact a study by the Social Science Research Network found that 65 percent of us are visual learners.

That’s why videos are such useful tools in teaching and learning, and that’s why when we came across a new video series called “Reaping the rewards of stem cell research” we were pretty excited. And to be honest there’s an element of self-interest here. The series focuses on letting people know all about the research funded by CIRM.

We didn’t make the videos, a group called Youreka Science is behind them. Nor did we pay for them. That was done by a group called Americans for Cures (the group is headed by Bob Klein who was the driving force behind Proposition 71, the voter-approved initiative that created the stem cell agency). Nonetheless we are happy to help spread the word about them.

The videos are wonderfully simple, involving just an engaging voice, a smart script and some creative artwork on a white board. In this first video they focus on our work in helping fund stem cell therapies for type 1 diabetes.

What is so impressive about the video is its ability to take complex ideas and make them easily understandable. On their website Youreka Science says they have a number of hopes for the videos they produce:

“How empowering would it be for patients to better understand the underlying biology of their disease and learn how new treatments work to fight their illness?

How enlightening would it be for citizens to be part of the discovery process and see their tax dollars at work from the beginning?

How rewarding would it be for scientists to see their research understood and appreciated by the very people that support their work?”

What I love about Youreka Science is that it began almost by chance. A PhD student at the University of California San Francisco was teaching some 5th graders about science and thought it would be really cool to have a way of bringing the textbook to life. So she did. And now we all get to benefit from this delightful approach.

Study Identifies Safer Stem Cell Therapies

To reject or not reject, that is the question facing the human immune system when new tissue or cells are transplanted into the body.

Stem cell-therapy promises hope for many debilitating diseases that currently have no cures. However, the issue of immune rejection has prompted scientists to carefully consider how to develop safe stem cell therapies that will be tolerated by the human immune system.

Before the dawn of induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs) were suggested as a potential source for transplantable cells and tissue. However, ESCs run into a couple of issues, including their origin, and the fact that ESC-derived cells likely would be rejected when transplanted into most areas of a human due to differences in genetic backgrounds.

The discovery of iPSCs in the early 2000’s gave new hope to the field of stem cell therapy. By generating donor cells and tissue from a patient’s own iPSCs, transplanting those cells/tissue back into the same individual shouldn’t – at least theoretically – cause an immune reaction. This type of transplantation is called “autologous” meaning that the stem cell-derived cells have the same genetic background as the person.

Unfortunately, scientists have run up against a roadblock in iPSC-derived stem cell therapy. They discovered that even cells derived from a patient’s own iPSCs can cause an immune reaction when transplanted into that patient. The answers as to why this occurs remained largely unanswered until recently.

In a paper published last week in Cell Stem Cell, scientists from the University of California, San Diego (UCSD) reported that different mature cell types derived from human iPSCs have varying immunogenic effects (the ability to cause an immune reaction) when transplanted into “humanized” mice that have a human immune system. This study along with the research conducted to generate the humanized mice was funded by CIRM grants (here, here).

In this study, retinal pigment epithelial cells (RPE) and skeletal muscle cells (SMC) derived from human iPSCs were transplanted into humanized mice. RPEs were tolerated by the immune system while SMCs were rejected. (Adapted from Zhao et al. 2015)

Scientists took normal mice and replaced their immune system with a human one. They then took human iPSCs generated from the same human tissue used to generate the humanized mice and transplanted different cell types derived from the iPSCs cells into these mice.

Because they were introducing cells derived from the same source of human tissue that the mouse’s immune system was derived from, in theory, the mice should not reject the transplant. However, they found that many of the transplants did indeed cause an immune reaction.

Interestingly, they found that certain mature cell types derived from human iPSCs created a substantial immune reaction while other cell types did not. The authors focused on two specific cell types, smooth muscle cells (SMC) and retinal pigment epithelial cells (RPE), to get a closer look at what was going on.

iPSC-derived smooth muscle cells created a large immune response when transplanted into humanized mice. However, when they transplanted iPSC-derived retinal epithelial cells (found in the retina of the eye), they didn’t see the same immune reaction. As a control, they transplanted RPE cells made from human ESCs, and as expected, they saw an immune response to the foreign ESC-derived RPE cells.


iPSC derived RPE cells (green) do not cause an immune reaction (red) after transplantation into humanized mice while H9 embryonic stem cell derived RPE cells do. (Zhao et al. 2015)

When they looked further to determine why the humanized mice rejected the muscle cells but accepted the retinal cells, they found that SMCs had a different gene expression profile and higher expression of immunogenic molecules. The iPSC-derived RPE cells had low expression of these same immunogenic molecules, which is why they were well tolerated in the humanized mice.

Results from this study suggest that some cell types generated from human iPSCs are safer for transplantation than others, an issue which can be addressed by improving the differentiation techniques used to produce mature cells from iPSCs. This study also suggests that iPSC-derived RPE cells could be a safe and promising stem cell therapy for the treatment of eye disorders such as age-related macular degeneration (AMD). AMD is a degenerative eye disease that can cause vision impairment or blindness and usually affects older people over the age of 50. Currently there is no treatment for AMD, a disease that affects approximately 50 million people around the world. (However there is a human iPSC clinical trial for AMD out of the RIKEN Center for Developmental Biology in Japan that has treated one patient but is currently on hold due to safety issues.)

The senior author on this study, Dr. Yang Xu, commented on the importance of this study in relation to AMD in a UCSD press release:

Dr. Yang Xu

Dr. Yang Xu

Immune rejection is a major challenge for stem cell therapy. Our finding of the lack of immune rejection of human iPSC-derived retinal pigment epithelium cells supports the feasibility of using these cells for treating macular degeneration. However, the inflammatory environment associated with macular degeneration could be an additional hurdle to be overcome for the stem cell therapy to be successful.

Xu makes an important point by acknowledging that iPSC-derived RPE cells aren’t a sure bet for curing AMD just yet. More research needs to be done to address other issues that occur during AMD in order for this type of stem cell therapy to be successful.


Related Links:

Throwback Thursday: Progress to a Cure for ALS

Welcome to our new “Throwback Thursday” (TBT) series. CIRM’s Stem Cellar blog has a rich archive of stem cell content that is too valuable to let dust bunnies take over.  So we decided to brush off some of our older, juicy stories and see what advancements in stem cell research science have been made since!

ALS is also called Lou Gehrig's disease, named after the famous American baseball player.

ALS is also called Lou Gehrig’s disease, named after the famous American baseball player.

This week, we’ll discuss an aggressive neurodegenerative disease called Amyotrophic Lateral Sclerosis or ALS. You’re probably more familiar with its other name, Lou Gehrig’s disease. Gehrig was a famous American Major League baseball player who took the New York Yankees to six world championships. He had a gloriously successful career that was sadly cut short by ALS. Post diagnosis, Gehrig’s physical performance quickly deteriorated, and he had to retire from a sport for which he was considered an American hero. He passed away only a year later, at the young age of 37, after he succumbed to complications caused by ALS.

A year ago, we published an interesting blog on this topic. Let’s turn back the clock and take a look at what happened in ALS research in 2014.

TBT: Disease in a Dish – Using Human Stem Cells to Find ALS Treatments

This blog featured the first of our scintillating “Stem Cells in Your face” video series called “Treating ALS with a Disease in a Dish.” Here is an excerpt:

Our latest video Disease in a Dish: That’s a Mouthful takes a lighthearted approach to help clear up any head scratching over this phrase. Although it’s injected with humor, the video focuses on a dreadful disease: amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig’s disease, it’s a disorder in which nerve cells that control muscle movement die. There are no effective treatments and it’s always fatal, usually within 3 to 5 years after diagnosis.

To explain disease in a dish, the video summarizes a Science Translation Medicine publication of CIRM-funded research reported by the laboratory of Robert Baloh, M.D., Ph.D., director of Cedars-Sinai’s multidisciplinary ALS Program. In the study, skin cells from patients with an inherited form of ALS were used to create nerve cells in a petri dish that exhibit the same genetic defects found in the neurons of ALS patients. With this disease in a dish, the team identified a possible cause of the disease: the cells overproduce molecules causing a toxic buildup that affects neuron function. The researchers devised a way to block the toxic buildup, which may point to a new therapeutic strategy.

New Stem Cell Discoveries in ALS Make Progress to Finding a Cure

So what’s happened in the field of ALS research in the past year? I’m happy to report that a lot has been accomplished to better understand this disease and to develop potential cures! Here are a few highlights that we felt were worth mentioning:

  • The Ice Bucket Challenge launched by the ALS Association is raising awareness and funds for ALS research.

    The Ice Bucket Challenge launched by the ALS Association is raising awareness and funds for ALS research.

    Ice Bucket Challenge. The ALS Association launched the “world’s largest global social media phenomenon” by encouraging brave individuals to dump ice-cold water on their heads to raise awareness and funds for research into treatments and cures for ALS. This August, the ALS Association re-launched the Ice Bucket Challenge campaign in efforts to raise additional funds and to make this an annual event.

  • ALS Gene Mapping. In a story released yesterday, the global biotech company Biogen is partnering with Columbia University Medical Center to map ALS disease genes. An article from Bloomberg Business describes how using Ice Bucket Money to create “a genetic map of the disease may help reveal the secrets of a disorder that’s not well understood, including how much a person’s genes contribute to the likelihood of developing ALS.” Biogen is also launching a clinical trial for a new ALS drug candidate by the end of the year.
  • New Drug target for ALS. Our next door neighbors at the Gladstone Institutes here in San Francisco published an exciting new finding in the journal PNAS in June. In collaboration with scientists at the University of Michigan, they discovered a new therapeutic target for ALS. They found that a protein called hUPF1 was able to protect brain cells from ALS-induced death by preventing the accumulation of toxic proteins in these cells. In a Gladstone press release, senior author Steve Finkbeiner said, “This is the first time we’ve been able to link this natural monitoring system to neurodegenerative disease. Leveraging this system could be a strategic therapeutic target for diseases like ALS and frontotemporal dementia.”
  • Stem cells, ALS, and clinical trials. Clive Svendsen at Cedars-Sinai is using gene therapy and stem cells to develop a cure for ALS. His team is currently working in mice to determine the safety and effectiveness of the treatment, but they hope to move into clinical trials with humans by the end of the year. For more details, check out our blog Genes + Cells: Stem Cells deliver genes as drugs and hope for ALS.

These are only a few of the exciting and promising stories that have come out in the past year. It’s encouraging and comforting to see, however, that progress towards a cure for ALS is definitely moving forward.

Alzheimer’s Nightmare Spurs Comedy Fundraiser to Help Caregivers – New Video

You could have heard a pin drop in the auditorium. The audience of young stem cell researchers was gripped by every word of Lauren Miller’s heartbreaking story about the impact that Alzheimer’s disease has had on her family. Only a child when her grandfather was diagnosed with and later died of Alzheimer’s, she mistook his symptoms, like repeating stories over and over, as his way of making her laugh.

Lauren was fifteen and much more aware of the brutality of the disease when her grandmother, the vibrant family matriarch, was diagnosed with Alzheimer’s and soon, ”stopped talking, stopped walking and eventually curled up in a ball and stayed that way for the last, many months of her life.”

Miller, a screenwriter and film actress, is the Alzheimer’s patient advocate member of CIRM’s Board. Last month, she was the opening speaker at the 2015 CIRM Bridges Trainee Meeting, a two-day event which showcases the work of undergraduate and Master’s level students who, through the support of the Bridges program, conducted stem cell research at world class research institutes in California. This video recording of Lauren’s talk is a great watch but keep a hanky near by:

Her presentation clearly resonated with the students, likely because their internships were mostly centered around the laboratory bench, and Lauren’s story provided a personal, first-hand account of a disease that could one day be treated by stem cell-based therapies. Also, Lauren was just about their age when, sadly, she first realized that her mom was showing the signs of early onset Alzheimer’s. Her memory of this moment is crushing:

“I first noticed it the weekend of my college graduation. She told me the same stories a few times and deep down inside I was devastated. I said nothing to anyone. Maybe if I pretended it didn’t happen, it wouldn’t be real. Maybe it was a one-time thing and it would just go away. Of course, it didn’t go away.”

Out of this darkness, Lauren has become a source of unwavering support for other families and caregivers who are beaten down by this disease on a daily basis. She and her husband Seth Rogen founded Hilarity for Charity which she says aims, “to raise awareness about Alzheimer’s among young adults and to support those who are going through it.” In only three and a half years, Hilarity for Charity has raised almost $3 million. Recently they launched a partnership with Home Instead Senior Care and in the past six months have funded 8000 hours of free at home care to give Alzheimer’s caregivers a much needed break. For me, one of the most poignant sections of Lauren’s talk is when she read a note from one of the recipients of these grants:

“The words, ‘thank you’, just don’t seem to be enough to express my heartfelt appreciation. I’ve barely been out of Sue’s sight since 2006 and our world has shrunk to the size of her bedroom and bath with conversations from babbling to hysteria. Please accept my total gratitude for this chance to join humanity again.”

At CIRM, our Board has awarded close to $55 million to stem cell related Alzheimer’s research. These cutting edge research projects aim to gain a better understanding of the disease and to progress stem cell-based treatments into clinical trials. Here’s hoping for an accelerated cure for Alzheimer’s to end the suffering of both patients and caregivers.

Related Links:

Stories of Hope: Lauren Miller
Stories of Hope: Dick Mora
CIRM Alzheimer’s Disease Program Fact Sheet
Video: Alzheimer’s Stem Cell Research: Ask the Expert – Larry Goldstein, UCSD
Video: Neural Stem Cells Reverse Alzheimer’s-Like Symptoms

A Stem Cell Summer with Taylor Swift, Jay-Z, and Carly Rae Jepsen (New Videos)

Was that a stem cell conference or a film festival?

It’s a question that may have been on some attendees’ minds last Friday at CIRM’s Creativity Day in San Mateo. The event showcased the accomplishments of about 70 high school students who did cutting-edge stem cell research as part of a CIRM-funded summer internship program at nine world-class institutions in California. The remarkable, young students gave graduate-level research presentations and showed off posters of their scientific findings to their lab mentors, the CIRM team, and proud family members.

While the main focus of the internship was lab research, we also included a social media assignment that asked students to capture their internship experiences by writing blogs, taking Instagram photos, or making movies. And just as the student poured their excitement, smarts, and hard work into their research, they also went all-in with the social media challenge.

I don’t know how they found the time, but eight videos were submitted in all – the most yet since the program started. And they’re fabulous! The CIRM team members who voted on the best videos were blown away by the inventiveness and artistry of the videos. Many students parodied popular songs by the likes of Taylor Swift, Jay-Z and Carly Rae Jepsen. They went above and beyond choreographing their own dance routines in the lab and injecting stem cell science into the lyrics. There was even a parody of the Jerry Seinfeld show called “Cirmfeld”.

The best social media submissions in each category were recognized at the Creativity Day (we blogged about the best blog yesterday). It was a very tough choice deciding on the best video, but in the end we choose one winner and two honorable mentions. In that moment just before the winner was announced, the students were holding their collective breaths and nervously sitting at the edge their seats. It really had the atmosphere of a film festival.

The winning video was a parody of Taylor Swift’s “Blank Space” by Vanessa Arreola & Camilia Kacimi who did their internships at the Gladstone Institutes in San Francisco. The duo shot, edited and scripted the video themselves. Their work is a great example of an effective way to communicate science to the public: start with a subject people know about, add creativity and humor, and teach some science along the way. Watch the video here:

The two honorable mentions also did fantastic jobs communicating science in an accessible way. The high school interns at City of Hope parodied Carly Rae Jepsen’s “I Really Like You” with their beautifully shot and edited video, “We’re Really Close (To a Breakthrough)”:

The students at Stanford also parodied Taylor Swift but in addition they threw down some fierce lyrics in their parody of a Jay-Z and Kayne West track. I do believe it’s the world’s first rap to include a reference to renown Stanford stem cell researcher, Irv Weissman:

You can watch all the videos on CIRMTV, the agency’s YouTube channel.

Congratulations and best of luck to all of the Creativity students. The future is bright for stem cell science!

New Video: Defeating Sickle Cell Disease with Stem Cells + Gene Therapy

Suffering with an incurable illness is no laughing matter. But last year when we debuted the pilot episode of Stem Cells in Your Face, a lighthearted video series that describes specific diseases and explains the latest progress in stem cell-based therapies, we hoped that a mix of science and humor would help make the information stick in the minds of our viewers. We were thrilled, based on your comments, that you enjoyed watching Treating ALS with a Disease in a Dish as much as we enjoyed producing it and that you wanted to see more:

“Very informative yet easy to understand pilot episode! Hope to see more in this series soon!” “Might I suggest highlighting a different disease CIRM focuses on in each video?”

Ask and you shall receive. This week we’ve posted the second installment: Defeating Sickle Cell Disease with Stem Cells + Jean Gene Therapy which is being rolled out as a companion piece to our new blog feature series, Genes + Cells.

 The video highlights a CIRM-funded clinical trial at UCLA that is testing a stem cell and gene therapy treatment for sickle cell disease. This awful genetic disorder causes red blood cells to assume a sickle shape, clogging blood vessels and producing episodes of excruciating pain, called crises, and leading to progressive organ damage. By twenty years of age about 15 percent of people with sickle cell disease have had major strokes and by 40 almost half of the patients have significant mental dysfunction. The disease strikes one in 500 African Americans and 1 in 36,000 Hispanic people. A standard treatment for sickle cell disease is a blood transfusion but the benefits are short-lived and require repeated procedures. Bone marrow transplants can be curative but they require a well-matched blood donor which is hard to find and can still be very risky. The UCLA team, on the other hand, aims to correct the sickle cell genetic mutation within the blood stem cells of the patient, which in theory could provide a life-long supply of normal shaped red blood cells. Don Kohn, the lead scientist on the team, explains their strategy in the video:

“The approach that we’re looking at would be to take the patient’s own bone marrow, isolate the [blood] stem cells, in the laboratory put in the gene we’ve been working on that prevents the red blood cells from sickling. So transplanting their own bone marrow back to them in theory should be safe, we don’t have to worry about rejection.“

If all goes well, sickle cell disease may soon be a thing of the past. As patient advocate Adrienne Shapiro has so eloquently stated in a previous Stories of Hope blog post:

“It’s my true belief that I’m going to be the last woman in my family to have a child with sickle cell disease. My afflicted daughter is going to be the last child to suffer, and my other daughter [who does not have the disease but carries the sickle cell mutation] is going to be the last one to fear [passing on the disease to her children]. Stem cells are going to fix this for us and many other families.”

This clinical trial represents one of the first trials to be part of CIRM’s Alpha Stem Cell Network. To learn more, visit our Alpha Clinic webpage. And for more details about CIRM-funding of sickle cell disease research visit these pages:

Clearing up chemobrain: cancer therapy-induced memory problems reversed by stem cells

You’d think receiving a cancer diagnosis and then suffering through chemo and/or radiation therapy would be traumatic enough. But as many as 75% of cancer survivors are afflicted by memory and attention problems long after their cancer therapy.

This condition, often called “chemobrain”, shouldn’t be misunderstood as being confined to cancers of the brain. A 2012 analysis of nearly 200 women who had been treated with chemotherapy for breast cancer showed they had ongoing memory and information processing deficits that persisted more than twenty years after their last round of treatment. And young cancer survivors are particularly vulnerable to reduced IQs, nonsocial behavior and an extremely lowered quality of life.


CIRM grantee and UC Irvine professor Charles Limoli, PhD is senior author of this study

Chemotherapy drugs work by killing off cells that are dividing rapidly, a hallmark of cancer cells. But this brute force method also kills other rapidly dividing cells that are critical for normal bodily functions. In the case of chemobrain, it’s thought that damage to newly formed brain cells in the hippocampus, the memory center of the brain, is the culprit. A UC Irvine study published this week in Cancer Research supports that idea in experiments that test the effect of transplanting human nerve stem cells in rats. The research team leader Charles Limoli, a CIRM grantee and UC Irvine professor of radiation oncology, summarized the groundbreaking results in a press release (note: this study is not funded by CIRM):

“Our findings provide the first solid evidence that transplantation of human neural stem cells can be used to reverse chemotherapeutic-induced damage of healthy tissue in the brain.”

The novel place recognition test is evaluate memory function. Animal is initially presented with identical objects (red circles). Then a new object is introduced (blue square). A healthy mouse will investigate the blue square.

The novel place recognition test, one of several tests used in this study to evaluate memory function.  During training setup (left), the rodent is familiarized with identical objects (red circles). Later, rodent returns now in presence of a new object (blue square). A healthy mouse will investigate the new object during testing setup (right). Image credit:

So how the heck do you observe chemotherapy-induced cognitive problems in a rodent let alone show that stem cells can rescue the damage? In the study, the rats undergo a variety of recognition memory tasks after a typical chemotherapy drug treatment. For instance, in the novel place recognition test, an animal is familiarized with two identical objects inside a test “arena”. Later, the animal is returned to the arena but a new object is swapped in for one of the previous objects. Rats given chemotherapy treatment but no stem cell surgery (they’re implanted with a saline solution instead) do not show a preference for the novel object. But rats given chemotherapy and the human nerve stem cell surgery prefer the novel object. This novel seeking behavior is also seen in control rats given no chemotherapy. So these results demonstrate that the transplanted stem cells rescued normal memory recognition in the chemotherapy-treated rats.

The research team also saw differences within the brains of these groups of rats that match up with these behavioral results. First, they confirmed that the transplanted human stem cells had indeed survived and grafted into the rat brains and had matured into the correct type of brain cells. Next they looked at chemotherapy-induced inflammation of brain tissue. The brains of chemotherapy-treated rats with no stem cell transplantation showed increased number of active immune cells compared to the control and stem cell transplanted animals. In another experiment, a detailed analysis of the structure of individual nerve cells showed extensive damage in the chemotherapy treated rats compared to controls. Again, this damage was reversed in chemotherapy treated rats that also received the stem cell transplant.

Rat nerve cells (black structures) in memory center of the brain are damaged by chemotherapy (left); transplanting human nerve stem cells reverses the damage (right)

Rat nerve cells (black structures) in memory center of the brain are damaged by chemotherapy (left); transplanting human nerve stem cells reverses the damage (right). Image credit: Acharya et al. Cancer Research 75(4) p. 676

As many researchers can tell you, these exciting results in animals don’t guarantee a human therapy is around the corner. But still, says Limoli:

“This research suggests that stem cell therapies may one day be implemented in the clinic to provide relief to patients suffering from cognitive impairments incurred as a result of their cancer treatments. While much work remains, a clinical trial analyzing the safety of such approaches may be possible within a few years.”

For a more details about the role of stem cells in chemobrain, watch this recent presentation to the CIRM Governing Board by CIRM grantee and Stanford professor Michelle Monje.

Money matters: how investing in research advances stem cell science

Our goal at the stem cell agency is simple; to accelerate the development of successful therapies to patients with unmet medical needs. But on the way to doing that something interesting is happening; we’re helping advance the scientific understanding of stem cells and building a robust stem cell research community in California in the process.

You don’t have to take our word for it. A new paper in the journal Cell Stem Cell takes a look at the impact that state funding for stem cell research has had on scientific publications. The question the researchers posed was; have the states that fund stem cell research seen an increase in their share of scientific publications in the field? The answer, at least in California’s case, is absolutely yes.

Let’s back up a little. In the late 1990’s and early 2000’s the field of stem cell research was considered quite controversial, particularly when it came to human embryonic stem cells (hESCs). To help scientists get around some of the restrictions that were placed on the use of federal funds to do hESC research a number of states voted to provide their own funding for this work. This research focuses on four of the biggest supporters of this work: California, Connecticut, Maryland, and New York.

The researchers looked at the following factors:

  1. The percentage of scientific publications in the U.S.
  2. With at least one author from those four states.
  3. That focused on hESCs and induced pluripotent stem cells (iPSCs).
  4. Comparing the numbers from before the state funding kicked in to after.

Finally – stay with me here, we’re almost done – they compared those numbers to the number of publications for two other areas of non-controversial biomedical research, RNAi and cancer. For California the results were clear. The percentage of papers on RNAi and cancer from 1996 – 2013, that had at least one California author, stayed fairly consistent (between 15-18%). However, the percentage of papers on hESCs and iPSCS with a California author rose from zero in 1998 and 2006 (the year each was discovered) to a high of 45 percent in 2009. That has since dropped down a little but still remains consistently high.

Study graphic study code The article says the reason for this is really rather obvious: “that state funding programs appear to have contributed to over-performance in the field.”

“After the California Institute for Regenerative Medicine (CIRM) issued its first grants in April 2006, the share of articles acknowledging California funding increased rapidly. Between 2010 and 2013, approximately 55% of hESC-related articles published with at least one California author acknowledged state funding, suggesting that this funding program played an important role as California maintained and built upon its early leadership in the field.”

Connecticut also saw its share of publications rise, though not as dramatically as California. Maryland and New York, in contrast, saw their share of publications remain consistent. However, as the researchers point out, with California gobbling up so much more of the available space in these journals, the fact that both states kept their share consistent was an achievement in itself.

The researchers acknowledge that scientific publications are “only one measure of the impact of state science programs” and say it’s important we look at other measures as well – such as how many clinical trials arise from that research. Nonetheless they conclude by saying:

“This analysis illustrating the relative performance of states in the production of stem-cell-related research publications provides a useful starting point for policymakers and, potentially, voters considering the future of state stem cell funding efforts as well as others interested in state science and technology policy more generally.”