Listen Up: A stem cell-based solution for hearing loss

Can you hear me now?

If you’re old enough, you probably recognize this phrase from an early 2000’s Verizon Wireless commercial where the company claims to be “the nation’s largest, most reliable wireless network”. However, no matter how hard wireless companies like Verizon try, there are still dead zones where cell phone reception is zilch and you can’t in fact hear me now.

This cell phone coverage is a good analogy for the 5% of the world population, or 360 million people, that suffer from hearing loss. There are many causes for hearing loss including genetic predispositions, birth defects, constant exposure to loud noises, infectious diseases, certain drugs, ear infections and aging. There is no cure that fully restores hearing, but patients can benefit from hearing aids, cochlear implants and other hearing devices.

But listen to this. A new stem cell-based technique developed by the Massachusetts Eye and Ear Infirmary may restore hearing in patients with hearing loss. The team discovered that stem cells in the inner ear can be manipulated in a culture dish to expand and develop into large quantities of cochlear hair cells, which make it possible for your brain to detect sound. Their work was published this week in the journal Cell Reports.

In a previous study, the Boston team found that stem cells in the inner ears of mice could be directly converted into cochlear hair cells, but they weren’t able to generate enough hair cells to fully restore hearing in these mice. Building on this work, the team isolated these stem cells, which express a protein called LGR5, and developed an augmentation technique consisting of drugs and growth factors to expand these stem cells and then specialize them into larger populations of hair cells.

A new technique converts stems cells into hair cells. Image credit Will McLean, Albert Edge, Massachusetts Eye and Ear

A new technique converts stems cells into hair cells. Image credit Will McLean, Albert Edge, Massachusetts Eye and Ear.

From a single mouse cochlea, they made more than 11,500 hair cells using their new augmentation method, which is more than 50 times the number of hair cells they made using a more basic method.

In a news release, senior author on the study, Dr. Albert Edge, explained the importance of their findings for patients with hearing loss:

Albert Edge

Albert Edge

“We have shown that we can expand Lgr5-expressing cells to differentiate into hair cells in high yield, which opens the door for drug discovery for hearing. We hope that by stimulating these cells to divide and differentiate that we will improve on our previous results in restoring hearing. With this knowledge, we can make better shots on goal, which is critical for repairing damaged ears. We have identified the cells of interest and have identified the pathways and drugs to target to improve on previous results. These clues may lead us closer to finding drugs that could treat hearing loss in adults.”

Wishing You and Your Stem Cells a Happy Valentine’s Day!

cirm-valentines-day

Roses are Red, 

Violets are Blue,

 Let’s thank pluripotent stem cells,

For making humans like me and you

Happy Valentine’s Day from me and everyone at CIRM! Today, we are celebrating this day of love by sending our warmest wishes to you our readers. We’re grateful for your interest in learning more about stem cells and your steadfast support for the advancement of stem cell research.

We also want to wish a Happy Valentine’s Day to your stem cells, yes that’s right the stem cells you have in your body. Without pluripotent stem cells, which are embryonic cells that generate all the cells in your body, humans wouldn’t exist. And without adult stem cells, which live in your tissues and organs, we wouldn’t have healthy, functioning bodies.

So, as you’re wishing your loved ones, friends, and colleagues a Happy Valentine’s Day, take a moment to thank your body and the stem cells living in it for keeping you alive.

I’ll leave you with a few Valentine’s Day themed stem cell blogs for you to enjoy. Have a wonderful day!


Valentine’s Day Themed Blogs:

1) Toronto Scientists Have an Affair with the Heart by OIRMexpression

Ventricular heart muscle cells. Image courtesy of Dr. Michael Laflamme

Ventricular heart muscle cells. Image courtesy of Dr. Michael Laflamme

2) A Cardiac Love Triangle: How Transcription Factors Interact to Make a Heart by the Stem Cellar

© Gladstone Institutes photo credit: Kim Cordes / Gladstone Institute Lay Description: In this image, human embryonic stem cells have been differentiated into cardiomyocytes, or heart muscle cells, and stained to show the expression of cardiac Troponin T (red), a protein that helps cardiomyocytes to contract, and cell nuclei (blue). Scientific Description: Cultured human iPSCs reprogrammed into CMs. Stain for cTnT (red), and DAPI (blue). Original caption: cardiomyocytes.tif

Heart cells made from human induced pluripotent stem cells. © Gladstone Institutes
photo credit: Kim Cordes / Gladstone Institute

3) Stem Cells on Valentine’s Day: Update on Cardiac Regenerative Medicine by Paul Knoepfler on the Niche Blog

4) Hope For Broken Hearts this Valentine’s Day – a Clinical Trial to Repair the Damage by the Stem Cellar


Special thanks to Samantha Yammine for letting us her her “Icy Astrocytes” photo in our Valentine’s Day graphic.

Stem Cell Stories That Caught our Eye: Making blood and muscle from stem cells and helping students realize their “pluripotential”

Stem cells offer new drug for blood diseases. A new treatment for blood disorders might be in the works thanks to a stem cell-based study out of Harvard Medical School and Boston Children’s hospital. Their study was published in the journal Science Translational Medicine.

The teams made induced pluripotent stem cells (iPSCs) from the skin of patients with a rare blood disorder called Diamond-Blackfan anemia (DBA) – a bone marrow disease that prevents new blood cells from forming. iPSCs from DBA patients were then specialized into blood progenitor cells, the precursors to blood cells. However, these precursor cells were incapable of forming red blood cells in a dish like normal precursors do.

Red blood cells were successfully made via induced pluripotent stem cells from a Diamond-Blackfan anemia patient. Image: Daley lab, Boston Children’s

Red blood cells were successfully made via induced pluripotent stem cells from a Diamond-Blackfan anemia patient. Image: Daley lab, Boston Children’s

The blood progenitor cells from DBA patients were then used to screen a library of compounds to identify drugs that could get the DBA progenitor cells to develop into red blood cells. They found a compound called SMER28 that had this very effect on progenitor cells in a dish. When the compound was tested in zebrafish and mouse models of DBA, the researchers observed an increase in red blood cell production and a reduction of anemia symptoms.

Getting pluripotent stem cells like iPSCs to turn into blood progenitor cells and expand these cells into a population large enough for drug screening has not been an easy task for stem cell researchers.

Co-first author on the study, Sergei Doulatov, explained in a press release, “iPS cells have been hard to instruct when it comes to making blood. This is the first time iPS cells have been used to identify a drug to treat a blood disorder.”

In the future, the researchers will pursue the questions of why and how SMER28 boosts red blood cell generation. Further work will be done to determine whether this drug will be a useful treatment for DBA patients and other blood disorders.

 

Students realize their “pluripotential”. In last week’s stem cell stories, I gave a preview about an exciting stem cell “Day of Discovery” hosted by USC Stem Cell in southern California. The event happened this past Saturday. Over 500 local middle and high school students attended the event and participated in lab tours, poster sessions, and a career resource fair. Throughout the day, they were engaged by scientists and educators about stem cell science through interactive games, including the stem cell edition of Family Feud and a stem cell smartphone videogame developed by USC graduate students.

In a USC press release, Rohit Varma, dean of the Keck School of Medicine of USC, emphasized the importance of exposing young students to research and scientific careers.

“It was a true joy to welcome the middle and high school students from our neighboring communities in Boyle Heights, El Sereno, Lincoln Heights, the San Gabriel Valley and throughout Los Angeles. This bright young generation brings tremendous potential to their future pursuits in biotechnology and beyond.”

Maria Elena Kennedy, a consultant to the Bassett Unified School District, added, “The exposure to the Keck School of Medicine of USC is invaluable for the students. Our students come from a Title I School District, and they don’t often have the opportunity to come to a campus like the Keck School of Medicine.”

The day was a huge success with students posting photos of their experiences on social media and enthusiastically writing messages like “stem cells are our future” and “USC is my goal”. One high school student acknowledged the opportunity that this day offers to students, “California currently has biotechnology as the biggest growing sector. Right now, it’s really important that students are visiting labs and learning more about the industry, so they can potentially see where they’re going with their lives and careers.”

You can read more about USC’s Stem Cell Day of Discovery here. Below are a few pictures from the event courtesy of David Sprague and USC.

Students have fun with robots representing osteoblast and osteoclast cells at the Stem Cell Day of Discovery event held at the USC Health Sciences Campus in Los Angeles, CA. February 4th, 2017. The event encourages students to learn more about STEM opportunities, including stem cell study and biotech, and helps demystify the fields and encourage student engagement. Photo by David Sprague

Students have fun with robots representing osteoblast and osteoclast cells at the USC Stem Cell Day of Discovery. Photo by David Sprague

Dr. Francesca Mariana shows off a mouse skeleton that has been dyed to show bones and cartilage at the Stem Cell Day of Discovery event held at the USC Health Sciences Campus in Los Angeles, CA. February 4th, 2017. The event encourages students to learn more about STEM opportunities, including stem cell study and biotech, and helps demystify the fields and encourage student engagement. Photo by David Sprague

Dr. Francesca Mariana shows off a mouse skeleton that has been dyed to show bones and cartilage. Photo by David Sprague

USC masters student Shantae Thornton shows students how cells are held in long term cold storage tanks at -195 celsius at the Stem Cell Day of Discovery event held at the USC Health Sciences Campus in Los Angeles, CA. February 4th, 2017. The event encourages students to learn more about STEM opportunities, including stem cell study and biotech, and helps demystify the fields and encourage student engagement. Photo by David Sprague

USC masters student Shantae Thornton shows students how cells are held in long term cold storage tanks at -195 celsius. Photo by David Sprague

Genesis Archila, left, and Jasmine Archila get their picture taken at the Stem Cell Day of Discovery event held at the USC Health Sciences Campus in Los Angeles, CA. February 4th, 2017. The event encourages students to learn more about STEM opportunities, including stem cell study and biotech, and helps demystify the fields and encourage student engagement. Photo by David Sprague

Genesis Archila, left, and Jasmine Archila get their picture taken at the USC Stem Cell Day of Discovery. Photo by David Sprague

New stem cell recipes for making muscle: new inroads to study muscular dystrophy (Todd Dubnicoff)

Embryonic stem cells are amazing because scientists can change or specialize them into virtually any cell type. But it’s a lot easier said than done. Researchers essentially need to mimic the process of embryo development in a petri dish by adding the right combination of factors to the stem cells in just the right order at just the right time to obtain a desired type of cell.

Making human muscle tissue from embryonic stem cells has proven to be a challenge. The development of muscle, as well as cartilage and bone, are well characterized and known to form from an embryonic structure called a somite. Researches have even been successful working out the conditions for making somites from animal stem cells. But those recipes didn’t work well with human stem cells.

Now, a team of researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA has overcome this roadblock by carrying out a systematic approach using human tissue. As described in Cell Reports, the scientists isolated somites from early human embryos and studied their gene activity. By comparing somites that were just beginning to emerge with fully formed somites, the researchers pinpointed differences in gene activity patterns. With this data in hand, the team added factors to the cells that were known to affect the activity of those genes. Through some trial and error, they produced a recipe – different than those used in animal cells – that could convert 90 percent of the human stem cells into somites in only four days. Those somites could then readily transform into muscle or bone or cartilage.

This new method for making human muscle will be critical for the lab’s goal to develop therapies for Duchenne muscular dystrophy, an incurable muscle wasting disease that strikes young boys and is usually fatal by their 20’s.

The new protocol turned 90 percent of human pluripotent stem cells into somite cells in just four days; those somite cells then generated (left to right) cartilage, bone and muscle cells.  Image: April Pyle Lab/UCLA

The new protocol turned 90 percent of human pluripotent stem cells into somite cells in just four days; those somite cells then generated (left to right) cartilage, bone and muscle cells. Image: April Pyle Lab/UCLA

Results are in: The Winners of our 2017 #StemCellResolution Campaign

We asked and you answered! In January, we launched our first Stem Cell Resolution campaign to raise awareness about the importance of stem cell research. We challenged scientists, students, institutes and the public to make a #StemCellResolution and share it on social media.

The goal of our campaign was to start a larger conversation about why stem cell research is important not just to advance science but to develop cures for diseases that currently have none.

Our campaign ran for the month of January, and we had global participation on multiple social media platforms including Twitter, Instagram, videos and blogs. Some resolutions involved answering important research questions while others involved empowering the public to pursue and understand scientific evidence to make their own informed decisions about the benefits of stem cell treatments for treating disease.

I was thoroughly impressed with everyone’s enthusiasm towards supporting and sharing this campaign that I plan to hold it again next year. But for now, I’ll announce the winners of our 2017 #StemCellResolution campaign. We picked the most inspiring resolution for each social media category and a few honorable mentions. The winner of each category will receive CIRM Stem Cell Champions t-shirts.

You can view the full list of this year’s stem cell resolutions on our Storify.


Twitter

Winner: Hamideh Emrani (@HamidehEmrani)

Hamideh is a science and technology communicator and the founder of Emrani Communications. 

Honorable Mention: Christine Liu (@Christineliuart)

Christine is a neuroscience phd student at UC Berkeley and a science communicator and artist.

Instagram

Winner: Pedro Soria Jr. (@shadowtype)

Pedro is a former CIRM Bridges student who is conducting stem cell research in neural regeneration at Western University in Southern California.

My Stem Cell Resolution for 2017 is to create a social media page dedicated to educating, enlightening and disseminating information about past, current, and future stem cell related studies to the general public, as well as those in science, in order to bring to light the importance of stem cell research. My objective is to bring people together regardless of whether or not they Originate from the natural sciences and spark an interest in this emerging field. Coming from a family where I'm first generation Mexican American and the only scientist has shown me the importance of communication amongst those that have little knowledge of the natural world especially people that come from countries that aren't scientifically advanced. Both my parents are born and raised in Michoacan, Mexico, in a small mountain town called Ario de Rosales. Back in my parents day, most people were farmers that worked from sun rise to sunset in order to feed and provide for their families. Naturally, they had little time for education because of the need to survive but had a positive work ethic, which I was lucky to inherit. My parents came to America for an opportunity to improve their situations and provide for themselves and families back home. They worked so hard to obtain what they have and to give me the chance they never had, which I'm so deeply grateful for each and every day of my life!! I had always felt destined for more than mediocre and enjoy taking on challenges to improve myself mentally, physically and spiritually. As a stem cell scientist, it is my responsibility to share my knowledge with everyone I encounter in order to bring change to this world. I wouldn't be where I am if it weren't for the support of my family, friends, professors, colleagues and of course #CIRM . Please join me on this journey and spread the word to anyone that will listen because we're all on this ride together in one way or another. That is my #stemcellresolution #soriaclan #bringingchange #cellculture Look out for my social media page #cellculture for all your stem cell info and check out the @cirm_stemcells to see what this beautiful institute is doing this year!!! #StemCellResolution

A post shared by Pedro Soria Jr. (@shadowtype) on

Video

Winner: Samantha Yammine (@SamanthaZY)

Samantha Yammine is a science communicator and a PhD candidate in Dr. Derek van der Kooy’s lab at the University of Toronto. You can learn more about Sam and her research on her website. She also recently wrote a guest blog for CIRM about a Keystone stem cell conference that you can find here.

Honorable Mentions: Paul Knoepfler (@pknoepfler)

Paul is a biomedical scientist at UC Davis, a science writer, advocate, and cancer survivor. He writes a popular stem cell blog called the Niche.

Honorable Mention: Catia B (@apulgarita)

Catia is a PhD student at MIT and is conducting research on programming & stem cells. She is originally from Portugal and has a personal blog about traveling and the PhD lifestyle.

Honorable Mention: Gladstone trainees (@Gladstone_GO)

Gladstone students and postdocs stepped up to the challenge and filmed stem cell resolutions about their research.

Blog

Winner: Sophie Arthur (@SophArthur)

Soph is a PhD student in Southampton, K studying embryonic stem cell metabolism. Her goal is to find ways to maintain the pluripotent quality of stem cells. She has a personal science communications blog called Soph Talks Science.

 An excerpt from Soph’s blog is below. I highly recommend reading the entire piece as it is very engaging and inspiring!

“For my Stem Cell Resolution – I couldn’t decide on one, so instead, I’ve made 4! Oops!

First, I want to raise awareness that stem cell biology is as important as stem cell treatments! There is lots of hype over stem cell treatments across the globe, but I want to stress that there are only a handful that have actually been approved! I could very well be biased as I’m studying stem cells and their biological mechanisms that exist normally in our bodies – but I want to stress the importance of this work. Simple biology – as I think it will hold the key to all the future stem cell medicine! Once we know how stem cells work in our bodies we can exploit that to make the treatments, or even learn more about our normal development!

 Honorable Mention: Stacey Johnson (@msstaceyerin)

Stacey is the Director of Communications and Marketing for CCRM, the Centre for Commercialization of Regenerative Medicine in Canada. She also is a regular contributor to CCRM’s Signals Blog.

“Since I’m not a scientist, a student or a patient, but I regularly communicate about stem cells to raise awareness and educate the public, my #stemcellresolution is to use this forum to spread the news – what I do best – about this fun and important challenge.”

Read Stacey’s full blog here.


 Thank you and see you next year!

Science communications is a vital tool that scientists and science enthusiasts need to leverage now more than ever to support stem cell research. Speaking out through social media or blogs is a great way to do this, and I want to congratulate all those that participated this year. I’m grateful for your support!

We look forward to doing this again next year and this time, you’ll have an entire year to ponder your next #StemCellResolution.

Curing the Incurable through Definitive Medicine

“Curing the Incurable”. That was the theme for the first annual Center for Definitive and Curative Medicine (CDCM) Symposium held last week at Stanford University, in Palo Alto, California.

The CDCM is a joint initiative amongst Stanford Healthcare, Stanford Children’s Health and the Stanford School of Medicine. Its mission is to foster an environment that accelerates the development and translation of cell and gene therapies into clinical trials.

The research symposium focused on “the exciting first-in-human cell and gene therapies currently under development at Stanford in bone marrow, skin, cardiac, neural, pancreatic and neoplastic diseases.” These talks were organized into four different sessions: cell therapies for neurological disorders, stem cell-derived tissue replacement therapies, genome-edited cell therapies and anti-cancer cell-based therapies.

A few of the symposium speakers are CIRM-funded grantees, and we’ll briefly touch on their talks below.

Targeting cancer

The keynote speaker was Irv Weissman, who talked about hematopoietic or blood-forming stem cells and their value as a cell therapy for patients with blood disorders and cancer. One of the projects he discussed is a molecule called CD47 that is found on the surface of cancer cells. He explained that CD47 appears on all types of cancer cells more abundantly than on normal cells and is a promising therapeutic target for cancer.

Irv Weissman

Irv Weissman

“CD47 is the first gene whose overexpression is common to all cancer. We know it’s molecular mechanism from which we can develop targeted therapies. This would be impossible without collaborations between clinicians and scientists.”

 

At the end of his talk, Weissman acknowledged the importance of CIRM’s funding for advancing an antibody therapeutic targeting CD47 into a clinical trial for solid cancer tumors. He said CIRM’s existence is essential because it “funds [stem cell-based] research through the [financial] valley of death.” He further explained that CIRM is the only funding entity that takes basic stem cell research all the way through the clinical pipeline into a therapy.

Improving bone marrow transplants

judith shizuru

Judith Shizuru

Next, we heard a talk from Judith Shizuru on ways to improve current bone-marrow transplantation techniques. She explained how this form of stem cell transplant is “the most powerful form of cell therapy out there, for cancers or deficiencies in blood formation.” Inducing immune system tolerance, improving organ transplant outcomes in patients, and treating autoimmune diseases are all applications of bone marrow transplants. But this technique also carries with it toxic and potentially deadly side effects, including weakening of the immune system and graft vs host disease.

Shizuru talked about her team’s goal of improving the engraftment, or survival and integration, of bone marrow stem cells after transplantation. They are using an antibody against a molecule called CD117 which sits on the surface of blood stem cells and acts as an elimination signal. By blocking CD117 with an antibody, they improved the engraftment of bone marrow stem cells in mice and also removed the need for chemotherapy treatment, which is used to kill off bone marrow stem cells in the host. Shizuru is now testing her antibody therapy in a CIRM-funded clinical trial in humans and mentioned that this therapy has the potential to treat a wide variety of diseases such as sickle cell anemia, leukemias, and multiple sclerosis.

Tackling stroke and heart disease

img_1327We also heard from two CIRM-funded professors working on cell-based therapies for stroke and heart disease. Gary Steinberg’s team is using human neural progenitor cells, which develop into cells of the brain and spinal cord, to treat patients who’ve suffered from stroke. A stroke cuts off the blood supply to the brain, causing the death of brain cells and consequently the loss of function of different parts of the body.  He showed emotional videos of stroke patients whose function and speech dramatically improved following the stem cell transplant. One of these patients was Sonia Olea, a young woman in her 30’s who lost the ability to use most of her right side following her stroke. You can read about her inspiring recover post stem cell transplant in our Stories of Hope.

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Joe Wu followed with a talk on adult stem cell therapies for heart disease. His work, which is funded by a CIRM disease team grant, involves making heart cells called cardiomyocytes from human embryonic stem cells and transplanting these cells into patient with end stage heart failure to improve heart function. His team’s work has advanced to the point where Wu said they are planning to file for an investigational new drug (IND) application with the US Food and Drug Administration (FDA) in six months. This is the crucial next step before a treatment can be tested in clinical trials. Joe ended his talk by making an important statement about expectations on how long it will take before stem cell treatments are available to patients.

He said, “Time changes everything. It [stem cell research] takes time. There is a lot of promise for the future of stem cell therapy.”

Good news from Asterias’ CIRM-funded spinal cord injury trial

This week in the stem cell field, all eyes are on Asterias Biotherapeutics, a California-based company that’s testing a stem cell based-therapy in a CIRM-funded clinical trial for spinal cord injury patients. The company launched its Phase 1/2a clinical trial back in 2014 with the goal of determining the safety of the therapy and the optimal dose of AST-OPC1 cells to transplant into patients.

astopc1AST-OPC1 cells are oligodendrocyte progenitor cells derived from embryonic stem cells. These are cells located in the brain and spinal cord that develop into support cells that help nerve cells function and communicate with each other.

Asterias is transplanting AST-OPC1 cells into patients that have recently suffered from severe spinal cord injuries in their neck. This type of injury leaves patients paralyzed without any feeling from their neck down. By transplanting cells that can help the nerve cells at the injury site reform their connections, Asterias hopes that their treatment will allow patients to regain some form of movement and feeling.

And it seems that their hope is turning into reality. Yesterday, Asterias reported in a news release that five patients who received a dose of 10 million cells showed improvements in their ability to move after six months after their treatment. All five patients improved one level on the motor function scale, while one patient improved by two levels. A total of six patients received the 10 million cell dose, but so far only five of them have completed the six-month follow-up study, three of which have completed the nine-month follow-up study.

We’ve profiled two of these six patients previously on the Stem Cellar. Kris Boesen was the first patient treated with 10 million cells and has experienced the most improvement. He has regained the use of his hands and arms and can now feed himself and lift weights. Local high school student, Jake Javier, was the fifth patient in this part of the trial, and you can read about his story here.

Kris Boesen, CIRM spinal cord injury clinical trial patient.

Kris Boesen, CIRM spinal cord injury clinical trial patient.

jake_javier_stories_of_hope

Jake Javier and his Mom

The lead investigator on this trial, Dr. Richard Fessler, explained the remarkable progress that these patients have made since their treatment:

“With these patients, we are seeing what we believe are meaningful improvements in their ability to use their arms, hands and fingers at six months and nine months following AST-OPC1 administration. Recovery of upper extremity motor function is critically important to patients with complete cervical spinal cord injuries, since this can dramatically improve quality of life and their ability to live independently.”

Asterias will continue to monitor these patients for changes or improvements in movement and will give an update when these patients have passed the 12-month mark since their transplant. However, these encouraging preliminary results have prompted the company to look ahead towards advancing their treatment down the regulatory approval pathway, out of clinical trials and into patients.

Asterias CEO, Steve Cartt, commented,

Steve Cartt, CEO of Asterias Biotherapeutics

Steve Cartt, CEO of Asterias Biotherapeutics

“These results to date are quite encouraging, and we look forward to initiating discussions with the FDA in mid-2017 to begin to determine the most appropriate clinical and regulatory path forward for this innovative therapy.”

 

Talking with the US FDA will likely mean that Asterias will need to show further proof that their stem cell-based therapy actually improves movement in patients, rather than the patients spontaneously regaining movement (which has been observed in patients before). FierceBiotech made this point in a piece they published yesterday on this trial.

“Those discussions with FDA could lead to a more rigorous examination of the effect of AST-OPC1. Some patients with spinal injury experience spontaneous recovery. Asterias has put together matched historical data it claims show “a meaningful difference in the motor function recovery seen to date in patients treated with the 10 million cell dose of AST-OPC1.” But the jury will remain out until Asterias pushes ahead with plans to run a randomized controlled trial.”

In the meantime, Asterias is testing a higher dose of 20 million AST-OPC1 cells in a separate group of spinal cord injury patients. They believe this number is the optimal dose of cells for achieving the highest motor improvement in patients.

2017 will bring more results and hopefully more good news about Asterias’ clinical trial for spinal cord injury. And as always, we’ll keep you informed with any updates on our Stem Cellar Blog.

Life after SPARK: CIRM high school intern gets prestigious scholarship to Stanford

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students.

Ranya Odeh

Ranya Odeh

Meet Ranya Odeh. She is a senior at Sheldon high school in Elk Grove, California, and a 2016 CIRM SPARK intern. The SPARK program provides stem cell research internships to underprivileged high school students at leading research institutes in California.

This past summer, Ranya worked in Dr. Jan Nolta’s lab at UC Davis improving methods that turn mesenchymal stem cells into bone and fat cells. During her internship, Ranya did an excellent job of documenting her journey in the lab on Instagram and received a social media prize for her efforts.

Ranya is now a senior in high school and was recently accepted into Stanford University through the prestigious QuestBridge scholarship program. She credits the CIRM SPARK internship as one of the main reasons why she was awarded this scholarship, which will pay for all four years of her college.

I reached out to Ranya after I heard about her exciting news and asked her to share her story so that other high school students could learn from her experience and be inspired by her efforts.


How did you learn about the CIRM SPARK program?

At my high school, one of our assignments is to build a website for the Teen Biotech Challenge (TBC) program at UC Davis. I was a sophomore my first year in the program, and I didn’t feel passionate about my project and website. The year after, I saw that some of my friends had done the CIRM SPARK internship after they participated in the TBC program. They posted pictures about their internship on Instagram, and it looked like a really fun and interesting thing to do. So I decided to build another website (one that I was more excited about) in my junior year on synthetic biology. Then I entered my website in the TBC and got first prize in the Nanobiotechnology field. Because I was one of the winners, I got the SPARK internship.

What did you enjoy most about your SPARK experience?

For me, it was seeing that researchers aren’t just scientists in white lab coats. The Nolta lab (where I did my SPARK internship) had a lot of personality that I wasn’t really expecting. Working with stem cells was so cool but it was also nice to see at the same time that people in the lab would joke around and pull pranks on each other. It made me feel that if I wanted to have a future in research, which I do, it wouldn’t be doing all work all the time.

What was it like to do research for the first time?

Ranya taking care of her stem cells!

Ranya taking care of her stem cells!

The SPARK internship was my first introduction to research. During my first experiment, I remember I was changing media and I thought that I was throwing my cells away by mistake. So I freaked out, but then my mentor told me that I hadn’t and everything was ok. That was still a big deal and I learned a lesson to ask more questions and pay more attention to what I was doing.

Did the SPARK program help you when you applied to college?

Yes, I definitely feel like it did. I came into the internship wanting to be a pharmacist. But my research experience working with stem cells made me want to change my career path. Now I’m looking into a bioengineering degree, which has a research aspect to it and I’m excited for that. Having the SPARK internship on my college application definitely helped me out. I also got to have a letter of recommendation from Dr. Nolta, which I think played a big part as well.

Tell us about the scholarship you received!

I got the QuestBridge scholarship, which is a college match scholarship for low income, high achieving students. I found out about this program because my career counselor gave me a brochure. It’s actually a two-part scholarship. The first part was during my junior year of high school and that one didn’t involve a college acceptance. It was an award that included essay coaching and a conference that told you about the next step of the scholarship.

The second part during my senior year was called the national college match scholarship. It’s an application on its own that is basically like a college application. I submitted it and got selected as a finalist. After I was selected, they have partner colleges that offer full scholarships. You rank your choice of colleges and apply to them separately with a common application. If any of those colleges want to match you and agree to pay for all four years of your college, then you will get matched to your top choice. There’s a possibility that more than one college would want to match you, but you will only get matched with the one that you rank the highest. That was Stanford for me, and I am very happy about that.

Why did you pick Stanford as your top choice?

It’s the closest university to where I grew up that is very prestigious. It was also one of the only colleges I’ve visited. When I was walking around on campus, I felt I could see myself there as a student and with the Stanford community. Also, it will be really nice to be close to my family.

What do you do in your free time?

I don’t have a lot of free time because I’m in Academic Decathalon and I spend most of my time doing that. When I do have free time, I like to watch Netflix, blogs on YouTube, and I try to go to the gym [laughs].

Did you enjoy posting about your SPARK internship on Instagram?

I had a lot of fun posting pictures of me in the lab on Instagram. It was also nice during the summer to see other SPARK students in different programs talk about the same things. We shared jokes about micropipettes and culturing stem cells. It was really cool to see that you’re not the only one posting nerdy science pictures. I also felt a part of a larger community outside of the SPARK program. Even people at my school were seeing and commenting on what I was doing.

UC Davis CIRM SPARK program 2016

UC Davis CIRM SPARK program 2016

I also liked that I got feedback about what I was doing in the lab from other SPARK students. When I posted pictures during my internship, I talked about working with mesenchymal stem cells. Because we all post to the same #CIRMSPARKlab hashtag, I saw students from CalTech commenting that they worked with those stem cells too. That motivated me to work harder and accomplish more in my project. Instagram also helped me with my college application process. I saw that there were other students in the same position as me that were feeling stressed out. We also gave each other feedback on college essays and having advice about what I was doing really helped me out.

Do you think it’s important for students to be on social media?

Yes, I think it’s important with boundaries of course. There are probably some people who are on social media too often, and you should have a balance. But it’s nice to see what other students are doing to prepare for college and to let loose and catch up with your friends.

What advice would you give to younger high school students about pursuing science?

I feel like students can’t expect things to be brought to them. If they are interested in science, they need to take the initiative to find something that they are going to want to do. The CIRM internship was brought to my attention. But I have friends that were interested in medicine and they found their own internships and ways to learn more about what they wanted to do. So my advice is to take initiative and not be scared of rejection, because if you’re scared of rejection you’re not going to do anything.

To hear more about Ranya’s SPARK internship experience, read her blog “Here’s what you missed this summer on the show coats.” You can also follow her on Instagram and Twitter. For more information about the CIRM SPARK internship program, please visit the CIRM website.


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Has the promise of stem cells been overstated?

One of the most famous stem cell scientists in the world said on Monday that the promise of stem cell treatments has in some ways been overstated.

In an interview with the New York Times, Dr. Shinya Yamanaka, one of the recipients of the 2012 Nobel Prize in Medicine for his discovery of induced pluripotent stem cells (iPS cells), said, “we can help just a small portion of patients by stem cell therapy.”

Shinya Yamanaka. (Image source: Ko Sasaki, New York Times)

Shinya Yamanaka. (Image source: Ko Sasaki, New York Times)

He explained that there are only 10 target diseases that he believes will benefit directly from stem cell therapies including, “Parkinson’s, retinal and corneal diseases, heart and liver failure, diabetes, spinal cord injury, joint disorders and some blood disorders. But maybe that’s all. The number of human diseases is enormous.”

This is a big statement coming from a key opinion leader in the field of stem cell research, and it’s likely to spur a larger conversation on the future of stem cell treatments.

Yamanaka also touched on another major point in his interview – progress takes time.

In the ten years since his discovery of iPS cells, he and other scientists have learned the hard way that the development of stem cell treatments can be time consuming. While autologous iPS cell treatments (making stem cell lines from a patient and transplanting them back into that patient) have entered clinical trials to treat patients with macular degeneration, a disease that causes blindness, the trials have been put on hold until the safety of the stem cell lines being used are confirmed.

At the World Alliance Forum in November, Yamanaka revealed that generating a single patient iPS cell line can cost up to one million dollars which isn’t feasible for the 1000’s of patients who need them. He admitted that the fate of personalized stem cell medicine, which once seemed so promising, now seems unrealistic because it’s time consuming and costly.

But with any obstacle, there is always a path around it. Under Yamanaka’s guidance, Japan is generating donor iPS cell lines that can be used to treat a large portion of the Japanese population. Yamanaka said that 100 lines would cover 100 million people in Japan and that 200 lines would be enough to cover the US population. iPS cell banks are being generated around the world, meaning that one day the millions of people suffering from the target diseases Yamanaka mentioned could be treated or even cured. Would this not fulfill a promise that was made about the potential of stem cell treatments?

Which brings me to my point, I don’t believe the promise of stem cells has been overstated. I think that it has yet to be realized, and it will take more research and more time to get there. As a community, we need to be understanding, patient, and supportive.

In my opinion (as a scientist aside from my role at CIRM), I believe that Yamanaka’s interview failed to reveal his optimism about the future of stem cell treatments. What I took from Yamanaka’s comments is that stem cell treatments can help a small number of patients with specific diseases right now. That’s not to say that stem cell research won’t produce promising treatments for other diseases in the future.

Retinal diseases and blood disorders are easier to target with stem cell treatments because only one type of cell needs to be replaced. It makes sense to tackle those diseases first and make sure that these stem cell treatments are effective and safe in patients before we focus on more complicated diseases where multiple cell types or organs are involved.

Part of the reason why scientists are unsure whether stem cell treatments can treat complex diseases is because we still don’t know the details of what causes these diseases. After we know more about what’s going wrong, including all the cell types and molecules involved, research might reveal new ways that stem cells could be used to help treat those diseases. Or on the other hand, stem cells could be used to model those diseases to help discover new drug treatments.

I’ve heard Yamanaka talk many times and recently I heard him speak at the World Alliance Forum in November, where he said that the two biggest hurdles we are facing for stem cell treatments to be successful is time and cost. After we overcome these hurdles, his outlook was optimistic that stem cell treatments could improve people’s lives. But he stressed that these advances will take time.

He shared a similar sentiment at the very end of the NY Times interview by referencing his father’s story and the decades it took to cure hepatitis C,

“You know, my father had a small factory. He injured his leg in the factory when I was in junior high. He had a transfusion, and he got hepatitis C. He passed away in 1989. Twenty-five years later, just two years ago, scientists developed a very effective cure. We now have a tablet. Three months and the virus is gone — it’s amazing. But it took 25 years. iPS cells are only 10 years old. The research takes time. That’s what everybody needs to understand.”

Yamanaka says more time is needed for stem cell treatments to become effective cures, but CIRM has already witnessed success. In our December Board meeting, we heard from two patients who were cured of genetic blood diseases by stem cell treatments that CIRM funded. One of them was diagnosed with severe combined immunodeficiency (SCID) and the other had chronic granulomatous disease (CGD). Both had their blood stem cells genetically engineered to removed disease-causing mutations and then transplanted back into their body to create a healthy immune system and cure them of their disease.

Hearing how grateful these patients and their families were to receive life-saving stem cell treatments and how this research brings new hope to other patients suffering from the same diseases, in my mind, fulfills the promise of stem cell research and makes funding stem cell treatments worth it.

I believe we will hear more and more of these success stories in the next decade and CIRM will most certainly play an important role in this future. There are others in the field who share a similar optimism for the future of stem cell treatments. Hank Greely, the Director for Law and the Biosciences at Stanford University, said in an interview with the Sacramento Bee about the future of CIRM,

Hank Greely, Stanford University

Hank Greely, Stanford University

“The next few years should determine just how good California’s investment has been. It is encouraging to see CIRM supporting so many clinical trials; it will be much more exciting when – and I do expect ‘when’ and not ‘if’ – one of those trials leads to an approved treatment.”

 


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Eye on the prize: two stem cell studies restore vision in blind mice

For the 39 million people in the world who are blind, a vision-restoring therapy would be the ultimate prize. So far, this prize has remained out of reach, but two studies published this week have entered the ring as promising contenders in the fight against blindness.

In the red corner, we have a study published in Stem Cell Reports from the RIKEN Institute in Japan led by scientist Masayo Takahashi. Her team restored vision in blind mice with an advanced stage of retinal disease by transplanting sheets of light-sensing photoreceptor cells that were made from induced pluripotent stem cells (iPSCs).

In the blue corner, we have a study published in Cell Stem Cell from the Buck Institute in California led by scientist Deepak Lamba. His team restored long-term vision in blind mice by transplanting embryonic stem cell-derived photoreceptor cells and preventing the immune system from rejecting the transplant.

Transplanting Retinal sheets

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Synaptic integration of graft retina into model mouse
Credit: RIKEN

Let’s first talk about the Riken study led by Masayo Takahashi. She is well known for her pioneering work on iPSC-derived treatments for macular degeneration – a disease that damages the retina and causes blindness.

In previous work, Takahashi and her team transplanted sheets of mouse stem cell-derived retinal progenitor cells, which mature into light-sensing cells called photoreceptors, into the eyes of mice. The cells within the sheet formed connections with the resident cells in the mouse eye, proving the feasibility of transplanting retinal sheets to restore vision.

In their current study, published in Stem Cell Reports, Takahashi’s team found that the retinal sheets could restore vision in mice that had a very severe form of retinal disease that left them unable to see light. After the mice received the retinal transplants, they responded to light, which they were unable to do previously. Like their other findings, they found that the cells in the transplant made connections with the host cells in the eye including nerve cells that send light-sensing signals to the brain.

First author on the study, Michiko Mandai explained the importance of their findings and their future plans in a news release,

“These results are a proof of concept for using iPSC-derived retinal tissue to treat retinal degeneration. We are planning to proceed to clinical trials in humans after a few more necessary studies using human iPSC-derived retinal tissue in animals. Clinical trials are the only way to determine how many new connections are needed for a person to be able to ‘see’ again.”

While excited by their results, Mandai and the rest of the RIKEN team aren’t claiming the prize for a successful treatment that will cure blindness in people just yet. Mandai commented,

“We cannot expect to restore practical vision at the moment. We will start from seeing a simple light, then possibly move on to larger figures in the next stage.”

Blocking the immune system

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Image showing transplanted GFP-expressing human stem cell derived photoreceptors (green) integrated in a host rodent retina stained for Otx2 (red).
Credit Jie Zhu, Buck Institute for Research on Aging

In the Buck Institute study, Lamba and his team took on the challenge of answering a controversial question about why retinal cell transplants typically don’t survive long-term in the eye. Some scientists think that the transplanted cells die off over time because they don’t integrate into the eye while others think that they are rejected and killed off by the immune system.

To answer this question, Lamba transplanted human embryonic stem cell-derived retinal cells into immunodeficient mice that lacked a protein receptor that’s vital for a functioning immune system. The retinal cells transplanted into immunodeficient mice survived much better than retinal cells transplanted into normal mice and developed into ten times as many photoreceptors that integrated themselves into the host eye.

Their next step was to transplant the retinal cells into mice that were blind and also lacked the same immune receptor as the other mice. After the transplant, the blind mice became responsive to light and showed brain activity associated with sensing light. Their newfound ability to see lasted for nine months to a year following the transplant.

Lamba believes that backing down the immune response is responsible for the long-term vision restoration in the blind mice. He explained the importance of their findings in a Buck Institute news release,

“That finding gives us a lot of hope for patients, that we can create some sort of advantage for these stem cell therapies so it won’t be just a transient response when these cells are put in, but a sustained vision for a long time. Even though the retina is often considered to be ‘immune privileged,’ we have found that we can’t ignore cell rejection when trying to transplant stem cells into the eye.”

In the future, Lamba will explore the potential for using drugs that target the specific protein receptor they blocked earlier to improve the outcome of embryonic stem cell-derived retinal transplants,

“We can also potentially identify other small molecules or recombinant proteins to reduce this interleukin 2 receptor gamma activity in the body – even eye-specific immune responses – that might reduce cell rejection. Of course it is not validated yet, but now that we have a target, that is the future of how we can apply this work to humans.”

Who will be the winner?

The Buck Institute study is interesting because it suggests that embryonic stem cell-based transplants combined with immunosuppression could be a promising strategy to improve vision in patients. But it also begs the question of whether the field should focus instead on iPSC-based therapies where a patient’s own stem cells are used to make the transplanted cells. This strategy would side step the immune response and prevent patients from a taking a lifetime of immunosuppressive drugs.

However, I’m not saying that RIKEN’s iPSC-based strategy is necessarily the way to go for treating blindness (at least not yet). It takes a lot of time and money to make iPSC lines and it’s not feasible given our current output to generate iPSC lines for every blind patient.

So, it sounds like a winner in this fight to cure blindness won’t be announced any time soon. In the meantime, both teams need to conduct further preclinical studies before they can move on to testing these treatments in human clinical trials.

Here at CIRM, we’re funding a promising Phase 1 clinical trial sponsored by jCyte for a form of blindness called Retinis Pigmentosa. Based on preliminary results with a small cohort of patient, the treatment seems safe and may even be showing hints of effectiveness in some patients.

Ultimately, more is better. As the number of stem cell clinical trials for blindness grows, the sooner we can find out which therapies work best for which patients.

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.

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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!