Unfolding Collaboration: New EuroStemCell video about promoting public engagement around stem cells

What does origami have to do with stem cells? Scientists at EuroStemCell, which is a partnership of more than 400 stem cell labs across Europe, are using origami and other creative activities to engage and educate the public about stem cells.

EuroStemCell’s goal is to “make sense of stem cells” by providing “expert-reviewed information and road-tested educational resources on stem cells and their impact on society.” Their educational resource page is rich with science experiments for kids, students and even adults. They also have science videos on topics ranging from what stem cells are to bioengineering body parts.

Unfolding Organogenesis

Recently EuroStemCell posted a video about how successful public engagement activities are based on strong collaborations between scientists, doctors, educators and communicators. This video was particularly powerful because it showed how good ideas can start from an individual, but great ideas happen when individuals work together to develop these initial ideas into activities that will really connect with their audience.

The video features Dr. Cathy Southworth who begins by telling the story of how she and her collaborators developed an origami activity called “Unfolding Organogenesis”. Southworth explains her rationale behind using paper to simulate how stem cells develop the tissues and organs in our body.

“I was mulling how to use a prop or activity to talk about stem cells, and it suddenly came to me that paper and origami is a bit like the process. The whole idea of starting from a blank slate. Depending on the instructions you follow, makes a different object. If you start with a stem cell, you can make any type of cell you find in the body. And that made me think it was quite a nice analogy to talk to the public about.”

Her initial idea was made a reality when Southworth began working with science and math educators Karen Jent and Tung Ken Lam. Together the team developed an interactive activity where people used paper to build 3D hearts that can actually beat.

Ken Lam making organ origami.

Southworth said that as a science communicator, educating the public is the focus of her work. But she also believes that educating scientists on how to communicate with the public effectively is equally important.

“Part of my job is to make sure that the scientists feel confident in the activities that they are going to deliver, and also that they are having a good time as part of the engagement work.”

The video also touches on important science communications tips like teaching scientists the art of storytelling. Southworth emphasized that having scientists talk about their personal story of why they are pursuing their research adds a human component that is key to connecting with their audience. Karen Jent also added that it’s important to understand your audience and their needs,

“You always have to think about what kind of audience you’re addressing and bear in mind that people aren’t all the same kinds of learners.”

Where are my stem cells?

CIRM is also dedicated to educating the public about stem cells and the importance of stem cell research. We have our own educational resources on our website, but we love to use materials from other organizations like EuroStemCell in our public engagement activities.

One of our favorite public engagement events is the Bay Area Science Festival Discovery Day held at AT&T park. This event attracts over 50,000 people, mainly young kids and their parents who are excited to learn about science and technology. At our booth, we’ve done a few different activities to teach kids about stem cells. One activity, which is great for young kids, is using Play-Doh to model embryonic development.

Teaching kids about embryonic development with Play-Doh! Photo: Todd Dubnicoff/CIRM

Another fun activity, this one developed by EuroStemCell, that we added last year was called “Where are my stem cells?”. It’s a game that teaches people that stem cells aren’t just found in the developing embryo. You’re given laminated cutouts of human organs and tissues, which you’re asked to place on a white board that has an outline of your body. While you are doing this, you learn that there are different types of adult stem cells that live in these tissues and organs and are responsible for creating the cells that make up those structures.

Where are your stem cells? A fun activity designed by EuroStemCell. Photo: Todd Dubnicoff/CIRM

If you’re interested in doing public engagement activities around stem cell education, the resources mentioned in this blog are a great start. I’d also recommend checking out the Super Cells, Power of Stem Cells exhibit, which is touring Europe, USA and Canada. It’s a wonderful interactive exhibit that explains the concept of stem cells and how they can be used to understand and treat disease. It’s also a great example of a collaboration between stem cell organizations including CIRM, CCRM, EuroStemCell, Catapult Cell Therapy and the Stem Cell Network.

We got a chance to check out the Super Cells exhibit last year when it visited the Lawrence Hall of Science in Berkeley. You can read more about it and see pictures in our blog.

Super Cells Exhibit. Photo: Todd Dubnicoff/CIRM

 

4 things to know about stem cell clinical trials [Video]

Every day, we receive phone calls and emails from people who are desperately seeking our help. Sometimes they reach out on their own behalf, though often it’s for a family member or close friend. In every case, someone is suffering or dying from a disorder that has no available cure or effective treatment and they look to stem cell treatments as their only hope.

It’s heartbreaking to hear these personal stories that are unfolding in real time. Though they contact us from a wide range of places about a wide range of disorders, their initial set of questions are often similar and go something like this:

  • “Where can I find stem cell clinical trial for my condition?”
  • “What are my chances of being cured?”
  • “How much does it cost to be in a clinical trial?”
  • “How can I be sure it’s safe?”

We think anyone thinking about taking part in a clinical trial should consider these important questions. So, in addition to providing answers as we receive them through phone calls and emails, we wanted to find a way to reach out to as many people as possible. The result? The four-minute animation video you can watch below:

As mentioned in the video, the answers to these questions are only the tip of the iceberg for finding out if a particular clinical trial is right for you. The website, A Closer Look at Stem Cells, produced by the International Society for Stem Cell Research (ISSCR), is an excellent source for more advice on what things you should know before participating in a stem cell clinical trial or any experimental stem cell treatment.

And visit the Patient Resources section of our website for even more practical information including our growing list of CIRM-funded clinical trials as well as trials supported by our Alpha Stem Cell Clinic Network.

Here’s a Fun Lab Tour Video Contest for Scientists

Scientists are often stereotyped as serious, focused individuals who spend most of their time pursuing their science with little time for anything else. Their research often is complex and hard for non-scientists to wrap their minds around. I’ve often heard my friends describe to me what they thought I did every day when I was in the lab. It was like a science fantasy story involving beakers full of brightly colored chemicals, explosions, and at the end, a cure for Parkinson’s disease…

But I am going to tell you a little known secret: scientists are normal people like everyone else. They aren’t magicians with special powers, and they know how to have fun while doing their research. The problem is that the public doesn’t know this because they don’t have the opportunity to visit a research laboratory and see scientists in action.

9ac56-paulknoepfler

Paul Knoepfler

UC Davis Professor Paul Knoepfler is addressing this issue with his new lab tour video contest that he recently announced on his blog, The Niche. He’s asking scientists to make short videos of their daily lives in the lab and post them on Twitter with the hashtag #labvideocontest. The winner will receive a cash prize and “free PR for their lab”. The videos can be serious or funny, but Paul asks contestants to use their imagination and think out of the box.

This contest will not only be a fun way for scientists to talk about their research and what they do every day, but it will also benefit the public who will get an inside view of what it’s like to be a scientist. The goal of science communications is to make science relatable to everyone, and this video contest on social media is a great example of new ways that scientists can connect with the public and make science more approachable.

You scientists out there can learn more about Paul’s contest and how to participate on his blog. The deadline to submit lab videos is March 15th, so you better get to work!

And if you need a place to start, watch our recent video featuring the McDevitt lab, a stem cell bioengineering lab at the Gladstone Institutes.

What’s Your 2017 Stem Cell Resolution?

January marks the beginning of a new year and is typically a time when people make resolutions to better themselves. This year at CIRM, we’re shaking things up and making stem cell resolutions.

What’s your #StemCellResolution?

Our goal is to raise awareness about the importance of funding stem cell research and accelerating the development of safe and effective stem cell treatments for patients. We want to promote this goal not only within the scientific and patient communities but also within the general public.

That’s why we are challenging you (yes you the reader) to come up with your own stem cell resolution for 2017 and share it with us on social media during the month of January.

It’s easy and fun to participate. All you need to do is think of a resolution about stem cell research. If you’re a scientist, it could be making a resolution to apply for funding for your newest stem cell project. Don’t know anything about stem cells? How about making a resolution to learn about stem cell research for a specific disease? The options are endless!

After you decide on your resolution, you can post a selfie, video, or stem cell resolution graphic that we’ve designed (available on our website  https://www.cirm.ca.gov/stemcellresolution) on Instagram, Facebook, or Twitter. Make sure to write your resolution in your post, include the hashtag #stemcellresolution, and tag CIRM’s social media accounts.

20161017_161337insta_scresolution_neurons

Have more than one resolution? No problem! Feel free to post as many stem cell resolutions during January as you want. We also encourage you to share this campaign with your friends and challenge them to participate.

Check out our video for more details on how to participate:

There be prizes!

At the end of January, we will pick the most inspiring stem cell resolutions and blog about them on the Stem Cellar. We’ll also send the people who wrote those resolutions CIRM Stem Cell Champions t-shirts.

So, what are you waiting for? We want to hear from you!

Easier, Cheaper Stem Cell-Based Heart Muscle Sets Stage for Large-Scale Drug Development

The great inventions – like the automobile, the Internet or aviation – are marked as important turning points in human history. But it’s usually the additional tinkering that goes on in the ensuing years after the initial invention that makes the technology feasible in terms of cost, reproducibility and mass production.

The same holds true for the Nobel prize winning induced pluripotent stem cell (iPS) technique. The sight of human iPS-derived heart muscle cells, or cardiomyocytes, beating in a petri dish brought a lot of early excitement in the late 2000’s (and still does today) about the potential of using human cells rather than animal models to screen for novel heart disease therapies and to test for drug toxicity.

And since iPS cells can be created directly from the skin or blood of a heart disease patient, it opened new opportunities to better understand the cellular basis of heart disease.

The Earth isn’t flat and neither is the heart
But the human heart is more than a two dimensional layer of cardiomyocytes in a petri dish. As a result, more complex three dimensional miniature heart structures that better mimic cardiac function have been developed over time. Now a CIRM-funded research team at the Gladstone Institutes has gone a step further and devised a “Micro-Heart Muscle” (µHM) technique that is easy to make and uses much fewer cells. The method detailed in Scientific Reports yesterday is poised to make large-scale, high-throughput drug and toxicology testing for heart disease therapies a reality.

Prior to this current publication, the Engineered Heart Muscle (EHM) has been the gold standard for petri dish models of human heart function. To better reflect the cellular environment of heart tissue than a simple layer of heart cells, EHM is composed of a mixture of iPS-derived cardiomyocytes, fibroblasts, and extracellular matrix, a natural scaffold that supports the heart’s cellular structure. These components are grown into 3D molds in a lab dish and embedded into posts that give the muscle cells something to contract against. This setup provides a means to do detailed analysis of the impact of drugs on heart muscle function. While these miniature EHM structures successfully produce physiologically relevant heart tissue for testing in the lab, they nonetheless carry some practical limitations. The complexity of the molds and the need for millions of cells for each EHM tissue makes the cost of large-scale drug development experiments too high. And the use of extracellular matrix would muck up the miniaturized instrumentation that is used for these therapy development efforts.

Dog bones: the key to easier, cheaper muscle tissue
The Gladstone team, led by Bruce Conklin, has overcome these challenges with their Micro-Heart Muscle product. With some educated trial and error, they zeroed in on a simple dog bone shaped mold to grow the mixture of cells in. The shape of the mold encouraged the muscle cells to self organize and grow into contracting tissue without the need of extracellular matrix. And better yet, less than 10,000 cells were needed to form each tissue. Here’s a cool video, recorded by first author Nathaniel Huebsch, of the cells in action:

These technical improvements of the Micro-Heart Muscle could help make large-scale, systematic approaches to study heart disease and toxicology a reality. As you read Conklin’s summary of the results in a Gladstone press release, you can hear his excitement about the future applications of this method:

conklin-profile.jpg

Bruce Conklin, Gladstone Institutes Senior Investigator

“The beauty of this technique is that it is very easy and robust, but it still allows you to create three-dimensional miniature tissues that function like normal tissues. Our research shows that you can create these complex tissues with a simple template that exploits the inherent properties of these cells to self-organize. We think that the micro heart muscle will provide a superior resource for conducting research and developing therapies for heart disease.”

 

Micro-Heart Muscle: the Model T of iPS innovations?
Karl Benz is generally credited as the inventor of the automobile, but a few years later it was Henry Ford’s efficient assembly line and manufacturing process that helped make mass production and affordability of the car possible. In a somewhat similar way, Shinya Yamanaka’s iPS technique will no doubt go down as one of the greatest inventions in the 21st century and maybe Conklin’s team’s Micro-Heart Muscle will also feature prominently in the history books as a follow up innovation that made the development of heart disease therapies possible.

Bruce-&-Nate-'web

Senior author Bruce Conklin and first author Nathaniel Huebsch [Photo: Chris Goodfellow]

Growing Stem Cell Research in California (Video)

How a Gladstone scientist is using bioengineering to push the pace of stem cell research

At CIRM, we strive to fund the most promising stem cell research and speed the advancement of stem cell treatments to patients who need them. Because we are a state agency, we generally focus on funding scientists, universities, and companies located in California. But we recognize that high quality stem cell research is ongoing throughout the country. That’s why CIRM has programs that fund research originating outside California and that recruit talented stem cell scientists to join our state’s vibrant stem cell community.

Today we want to share a video we produced titled, “Growing Stem Cell Research in California” that provides an example of how CIRM has catalyzed the growth of stem cell research by helping recruit Dr. Todd McDevitt, a leading biomedical engineer in stem cell research, to the Gladstone Institutes in San Francisco.

Todd started his lab at the Georgia Institute of Technology in Atlanta and moved to the Gladstone a year ago to conduct research using human pluripotent stem cells to engineer 3D micro-tissues for use in drug development and disease modeling. His move was made possible by a CIRM Research Leadership Award, which allowed the Gladstone to recruit Todd and is now his lab’s major source of funding.

Todd McDevitt, Gladstone Institutes

Todd McDevitt, Gladstone Institutes

With an expertise in tissue engineering, Todd and his team are collaborating with other researchers at the Gladstone on projects that use human stem cells to create organ-like tissues to advance research and therapeutic development for a wide range of areas including brain disease, heart disease and spinal cord injury.

Todd is a young and talented scientist who is using his expertise in bioengineering to push the pace of stem cell research ultimately, we hope, to improve human health. You can read more about Todd’s first year anniversary at the Gladstone in their latest news release.

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.

Picture1

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.

Ogawa_Award_Gladstone-0808

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.

Plath_iPS2

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.

RPE_1

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: