How a Soviet space craft proved an inspiration for CIRM’s latest Board member

blumenthal

George Blumenthal’s life changed on October 4, 1957. That’s the day the Soviet Union launched Sputnik, the world’s first artificial earth satellite. The beach ball-sized satellite marked the start of the space race between the US and the USSR. It also marked the start of Blumenthal’s fascination with science and space.

Fast forward almost 60 years and Dr. Blumenthal, now a world-renowned professor of astronomy and astrophysics and the Chancellor of U.C. Santa Cruz, has been named as the newest member of the CIRM governing Board.

California Lt. Governor Gavin Newsom made the appointment calling Dr. Blumenthal a world-class scientist and forward-looking administrator:

“As a Regent of the University of California, I have been impressed by his deep commitment to expanding educational opportunity for all California students and enhancing research opportunities. I am confident the Chancellor’s vision and leadership will be of immense benefit to the CIRM Board.”

In a news release Dr. Blumenthal said he is looking forward to being part of CIRM:

“The California Institute for Regenerative Medicine is doing outstanding work, and I am delighted to join the Board. CIRM support has advanced stem cell research at UC Santa Cruz and across the state. Public support for this work remains strong, and I look forward to playing a role in securing the future of the institute.”

sputnik

Sputnik

But getting back to Sputnik for a moment. In an article in Valley Vision, the newsletter for Joint Venture Silicon Valley, Dr. Blumenthal said the launch of Sputnik helped fuel his interest in science in general and space in particular.

“Sputnik had a profound effect on American science and it certainly played a part in my interest in space and physics all through high school, college and graduate school,” says Blumenthal. “I intended to become a particle physicist, but after a year in grad school I became more interested in space and astronomy, so I changed from studying the smallest things in the universe to the biggest, like galaxies.”

Dr. Blumenthal became the first in his family to graduate from college. He then went on to enjoy a successful career as a professor of astronomy and astrophysics. His research helped deepen our understanding of galaxies and the cosmos, including the role that dark matter plays in the formation of the structure of the universe. He became the chair of the California Association for Research in Astronomy (CARA), which manages the W. M. Keck Observatory near the summit of Mauna Kea in Hawaii. He also co-authored two of the leading astronomy textbooks, 21st Century Astronomy and Understanding our Universe.

Blumenthal joined the faculty of UC Santa Cruz in 1972 and was named chancellor in 2007. Throughout his career he has been a champion of diversity both at UCSC, where he created the Chancellor’s Advisory Council on Diversity, and throughout the U.C. system, where he served as a member of the Regents’ Study Group on Diversity.

Jonathan Thomas, Chair of the CIRM Board, welcomed Dr. Blumenthal, saying:

“We are honored to have someone with Dr. Blumenthal’s experience and expertise join the Board. As Chancellor at UCSC he has demonstrated a clear commitment to advancing world-class research and earned a reputation as a bold and visionary leader. We look forward to seeing those qualities in action to help advance CIRM’s mission.”

At CIRM we are shooting for the stars, aiming as high as we can to help accelerate stem cell treatements to patients with unmet medical needs. It will be nice having Dr. Blumenthal on Board to help guide us.

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.”

Stories that caught our eye: stem cell transplants help put MS in remission; unlocking the cause of autism; and a day to discover what stem cells are all about

multiple-sclerosis

Motor neurons

Stem cell transplants help put MS in remission: A combination of high dose immunosuppressive therapy and transplant of a person’s own blood stem cells seems to be a powerful tool in helping people with relapsing-remitting multiple sclerosis (RRMS) go into sustained remission.

Multiple sclerosis (MS) is an autoimmune disorder where the body’s own immune system attacks the brain and spinal cord, causing a wide variety of symptoms including overwhelming fatigue, blurred vision and mobility problems. RRMS is the most common form of MS, affecting up to 85 percent of people, and is characterized by attacks followed by periods of remission.

The HALT-MS trial, which was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), took the patient’s own blood stem cells, gave the individual chemotherapy to deplete their immune system, then returned the blood stem cells to the patient. The stem cells created a new blood supply and seemed to help repair the immune system.

Five years after the treatment, most of the patients were still in remission, despite not taking any medications for MS. Some people even recovered some mobility or other capabilities that they had lost due to the disease.

In a news release, Dr. Anthony Fauci, Director of NIAID, said anything that holds the disease at bay and helps people avoid taking medications is important:

“These extended findings suggest that one-time treatment with HDIT/HCT may be substantially more effective than long-term treatment with the best available medications for people with a certain type of MS. These encouraging results support the development of a large, randomized trial to directly compare HDIT/HCT to standard of care for this often-debilitating disease.”

scripps-campus

Scripps Research Institute

Using stem cells to model brain development disorders. (Karen Ring) CIRM-funded scientists from the Scripps Research Institute are interested in understanding how the brain develops and what goes wrong to cause intellectual disabilities like Fragile X syndrome, a genetic disease that is a common cause of autism spectrum disorder.

Because studying developmental disorders in humans is very difficult, the Scripps team turned to stem cell models for answers. This week, in the journal Brain, they published a breakthrough in our understanding of the early stages of brain development. They took induced pluripotent stem cells (iPSCs), made from cells from Fragile X syndrome patients, and turned these cells into brain cells called neurons in a cell culture dish.

They noticed an obvious difference between Fragile X patient iPSCs and healthy iPSCs: the patient stem cells took longer to develop into neurons, a result that suggests a similar delay in fetal brain development. The neurons from Fragile X patients also had difficulty forming synaptic connections, which are bridges that allow for information to pass from one neuron to another.

Scripps Research professor Jeanne Loring said that their findings could help to identify new drug therapies to treat Fragile X syndrome. She explained in a press release;

“We’re the first to see that these changes happen very early in brain development. This may be the only way we’ll be able to identify possible drug treatments to minimize the effects of the disorder.”

Looking ahead, Loring and her team will apply their stem cell model to other developmental diseases. She said, “Now we have the tools to ask the questions to advance people’s health.”

A Day to Discover What Stem Cells Are All about.  (Karen Ring) Everyone is familiar with the word stem cells, but do they really know what these cells are and what they are capable of? Scientists are finding creative ways to educate the public and students about the power of stem cells and stem cell research. A great example is the University of Southern California (USC), which is hosting a Stem Cell Day of Discovery to educate middle and high school students and their families about stem cell research.

The event is this Saturday at the USC Health Sciences Campus and will feature science talks, lab tours, hands-on experiments, stem cell lab video games, and a resource fair. It’s a wonderful opportunity for families to engage in science and also to expose young students to science in a fun and engaging way.

Interest in Stem Cell Day has been so high that the event has already sold out. But don’t worry, there will be another stem cell day next year. And for those of you who don’t live in Southern California, mark your calendars for the 2017 Stem Cell Awareness Day on Wednesday, October 11th. There will be stem cell education events all over California and in other parts of the country during that week in honor of this important day.

 

 

Mini-guts made from stem cells uncover mechanisms of viral infection in infants

Newborns: so precious, so vulnerable. Image: Wikimedia commons

Newborns: so precious, so vulnerable. Image: Wikimedia commons

Besides their chubby cheeks and cute little toes, I think what makes newborns so precious is how vulnerable they are in those first few days and months of life. For instance, infants are particularly easy targets for infections of the gut caused by enteroviruses. While healthy adults infected with these viruses may exhibit mild cold or flu-like symptoms, infants can have serious complications including sudden onset paralysis, infection of the heart and brain, even death.

Not much is known about how these viruses enter the gut and gain entry to other parts of the body. Reporting this week in PNAS, a research team at the Washington University School of Medicine in St. Louis used human stem cell-derived “mini-guts” to uncover some clues.

enteroid

Mini-gut grown from human intestinal stem cells. Image: Cliff Luke/Misty Good, U. Washington – St. Louis

The intestine is a very complex organ with several different cell types that work in concert to keep bacteria and viruses out, and to allow food to be absorbed into the bloodstream. This complexity has made it difficult to carry out human studies in the lab that adequately mimic enterovirus infection. To overcome these challenges, the team isolated stem cells from the small intestine of a premature infant and successfully generated mini-intestines in petri dishes.

The researchers then tested the ability of various enteroviruses to infect the mini-guts and observed they were most vulnerable to infection by enterovirus E11, the most common enterovirus infection seen in premature infants. The team went on to show that the E11 virus infects some cell types of the mini-gut but not others.

In a press release, Co-senior author Carolyn Coyne, an associate professor at the University of Pittsburgh School of Medicine, described the importance of this work for the 10 to 15 million enterovirus infections and tens of thousands of hospitalizations each year in the U.S.:

“Despite their major global impact, especially on the health of children, little is known about the route that these viruses take to cross the intestine, their primary point of entry. Our approach has for the first time shed some light on this process. This model also could be used for developing anti-enterovirus therapeutics targeting the gastrointestinal tract, given that no therapeutic approaches exist to combat infections of these viruses.”

Let’s Be Clear: Stem Cells and Popular Culture

The following is a guest blog from Matt Donne, PhD. Thoughts expressed here are not necessarily those of CIRM.

It was during winter break of my Junior year in college that the gap between the general public’s understanding of embryonic stem cell biology and the reality of that research quickly came into focus for me.

I was out to lunch with my grandmother and excited to see her to share my new research project I had started with human embryonic stem cells (hESCs). While enjoying our lunch together discussing school, relationships, and such, a friend of hers approached to say hello. Immediately my grandmother proclaimed, “This is my grandson Matthew and he is a scientist. He just started working with stem cells to cure cancer.”  Now this statement was not true, but harmless enough so I figured I would let it go. Her friend’s eyes immediately grew large and she quickly felt it necessary to educate us on what exactly I was doing by working with “stem cells”. In her friend’s words I was, “killing babies and sucking out their brains to make stem cells.”

My grandmother and I were both silenced and confused, for different reasons, as her friend quickly walked away in disgust. My grandmother asked concernedly if this was in fact true. I explained that this could not be farther from the truth, and that this friend was extremely misinformed. We then discussed the difference between a developing fetus and the 3 to 5 day old embryos from which these hESC lines were derived. We also discussed these embryos were donated by couples who seek in vitro fertilization (IVF) treatments. Specifically, the donated embryos were those which the couple no longer needed and therefore decided to donate them for research proposes to help advance both science and medicine rather than discard them. This fact-based explanation eased many of the fears my grandmother had as to the research. This, however, left in me a fear that over 10 years later I still see playing out in popular culture.

Most recently my frustration toward this misinformation came when I saw a posting by VICE of a carton entitled ‘Magical Stem Cells’. The cartoon was a truly gross and inaccurate representation of where embryonic stem cells are derived, as it portrayed a unicorn fetus essentially being harvested to create “magical” stem cells that can turn into any other cell, tissue or organ in the body. This is wholly inaccurate. It is possible that the cartoon was created to positively promote the potential of stem cell biology, however anyone somewhat versed in the field would find it misleading, disgusting, scary and dangerous.

Vice comic: Magical Stem Cells

Vice comic: Magical Stem Cells

Similarly, the creators of South Park several years back had an episode in which Christopher Reeves was essentially a spokesperson for the research and its potential to cure spinal cord injury. They equated stem cell therapies, like the VICE cartoon, to the use of fetal tissue for therapeutic purposes. Let’s be clear, stem cell biology and stem cell research does not universally mean the use of fetal tissue. In fact, most often the fields of stem cell biology are broken down into three main groups: hESCs, induced pluripotent stem cells (iPSCs, which are adult cells that have been re-engineered to have embryonic-like qualities), and the broader category of adult stem cells. Use of cells taken from aborted human fetuses, either for research or clinical trials, is in fact the exception to the rule.

The term “stem cell” was first used in 1877 when German biologist Ernst Haeckel wrote about a “stem cell” being the fertilized egg from which all cells of the placenta and body arise.1 In 1981, U.C. San Francisco’s Gail Martin became the first scientist to isolate pluripotent cells (which can turn into any other cell in the body) from mouse embryos and coined the term “embryonic stem cells” to describe them.2 It was not until 1998 that James Thomson created the first hESC lines.3

A few interesting facts about blastocyst stage embryos, which were the source of the first embryonic stem cell lines, are that they look the same in mice, humans, dogs, horses, and cows and are typically comprised of no more than several hundred cells. It is also important to note that embryonic stem cells, by definition, can only come from up to blastocyst stage embryos (about 5-7 days after fertilization). Cells taken from embryos older than the blastocyst stage have already begun specializing into specific cell lineages, and are no longer capable of making all cell types.

This, I think, is extremely important to emphasize, as too many people seem to believe that we get our embryonic stem cells from fetuses. I think it is also important to point out that now several groups have published on potential “embryo-safe” methods of embryonic stem cell derivation4-6, which use a single cell from the early, cleavage stage embryo for derivation. This removal of a single cell from such an early stage embryo has been demonstrated to have no negative consequences to the developing embryo, as it has been used for years in IVF clinics. Development of this technique in turn can help alleviate some of the ethical concerns that people have about the use of donated human embryos for research. Lastly, advances in the techniques and use of both iPSCs and adult stem cells alleviate any potential concerns raised by hESCs.

What I hope to achieve in this opinion piece is to raise a general awareness that some commonly held views on stem cells need to be overturned. This can only happen through continued open conversations and discussions. An important way to achieve this is through outreach and education of young students to get them excited about science and the potential of stem cell biology. Resources such as CIRM’s free online education portal and Outschool’s online teaching platform are great example of how to make this happen. Using social media, such as Facebook and Twitter, to post peer-reviewed publications or review articles is another way to make a positive impact.

There are so many amazing things happening in the various fields of stem cell biology that now, more than ever, it is important we lean on facts and push for communicating truths to further our progress of educating the public. What I ask of you at this point is to not sit back and shake your head when you see or read something you know is wrong, such as VICE’s “magical stem cells” cartoon. Please say something, and teach someone.   

Matt Donne

Matt Donne

Matt Donne recently finished his PhD in Developmental and Stem Cell Biology at the University of California, San Francisco, where he was awarded a CIRM Fellowship. Previously he was a CIRM student at San Francisco State University.  He has shared his passion for stem cell biology with students of all ages for over 10 years. His passion for stem cell biology and animals has brought him to VitroLabs, where he is changing how leather is manufactured.


Citations:

1          Ramalho-Santos, M. & Willenbring, H. On the origin of the term “stem cell”. Cell Stem Cell 1, 35-38, doi:10.1016/j.stem.2007.05.013 (2007).

2          Martin, G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78, 7634-7638 (1981).

3          Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147 (1998).

4          Klimanskaya, I., Chung, Y., Becker, S., Lu, S. J. & Lanza, R. Human embryonic stem cell lines derived from single blastomeres. Nature 444, 481-485, doi:10.1038/nature05142 (2006).

5          Zdravkovic, T. et al. Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification. Development 142, 4010-4025, doi:10.1242/dev.122846 (2015).

6          Chung, Y. et al. Human Embryonic Stem Cell Lines Generated without Embryo Destruction. Cell Stem Cell 2, 113-117, doi:http://dx.doi.org/10.1016/j.stem.2007.12.013 (2008).

A ‘Call to Action’ for change at the FDA

hd

It’s bad enough to have to battle a debilitating and ultimately deadly disease like Huntington’s disease (HD). But it becomes doubly difficult and frustrating when you feel that the best efforts to develop a therapy for HD are running into a brick wall.

That’s how patients and patient advocates working on HD feel as they see the Food and Drug Administration (FDA) throw up what they feel are unnecessary obstacles in the way of promising research.

So the group Help 4HD International has decided to push back, launching an online campaign to get its supporters to pressure the FDA into taking action. Any action.

Posing the question “Does the FDA understand that time is something we simply don’t have?” Help 4HD is urging people to write to the FDA:

“We have heard the FDA say they feel like our loved ones have quality of life at the end stages of HD. We have heard them say people with HD get to live for 20 years after diagnosis. It seems like the FDA doesn’t understand what we are having to live with generation after generation. We have seen HD research die because the researcher couldn’t get an IND (Investigational New Drug, or approval to put a new drug into clinical trials) from the FDA. We have seen trials that should be happening here in the USA move to other countries because of this. We have seen the FDA continue to put up delays and roadblocks. We are lucky to have amazing research going on for HD/JHD (juvenile HD) right now, but what is that research worth if the FDA doesn’t let it go into clinical trials? Drug development is a business and costs millions of dollars. If the FDA continues to refuse INDs, the fear is that companies will stop investing in HD research. This is a fate that we can’t let happen! We need to write to the FDA and let them know our frustrations and also help them understand our disease better.”

The group has drafted a sample letter for people to use or adapt as they see fit. They’ve even provided them with the address to mail the letter to. In short, they are making it as easy as possible to get as many people as possible to write to the FDA and ask for help.

The HD community is certainly not the only one frustrated at the FDA’s  glacial pace of approval of for clinical trials. That frustration is one of many reasons why Congress passed the 21st Century Cures Act late last year. That’s also the reason why we started our Stem Cell Champions campaign, to get the FDA to create a more efficient, but no less safe, approval process.

Several of our most active Stem Cell Champions – like Frances Saldana, Judy Roberson and Katie Jackson – are members of the HD Community. Last May several members of the CIRM Team attended the HD-Care Conference, held to raise awareness about the unmet medical needs of this community. We blogged about it here.

While this call to action comes from the HD community it may serve as a template for other organizations and communities. Many have the same frustrations at the slow pace of approval of therapies for clinical trials.

We are hoping the 21st Century Cures Act will lead to the desired changes at the FDA. But until we see proof that’s the case we understand and support the sense of urgency that the HD community has. They don’t have the luxury of time.

 

 

Stem Cells Profiles in Courage: Frank’s final gift

frank-st-clair

Not every story has a happy ending. But they do all have something to teach us. In the case of Frank St. Clair the lesson was simple: live life fully and freely, love those around you, and never give up.

We were fortunate enough to get to know Frank as one of the people we profiled in our 2016 Annual Report. Frank was a patient in a clinical trial we are funding to test a new kind of bioengineered vein needed by people undergoing hemodialysis, the most common form of dialysis.

It was an all too brief friendship. Frank passed away on December 17th due to complications from heart disease. But in that time he touched us with his warmth, his kindness, his sense of humor and his generosity. Frank never gave up. He kept fighting to the end. His courage, and compassion for others is a reminder to us that we need to work as hard as we can, to bring treatments to those who need them most.

This is Frank’s story, in his own words:

“I have kidney disease. Had it about four years. When I first started dialysis I had a shunt in my chest.  I had to be careful with the shunt, especially at night, in case I pulled it out. It kept clogging up on me and I’d have to go in and get it reopened and that was a terrible thing.

One time when they were opening up the shunt in my chest I ran into the doctor and I got talking to him. He knew how miserable I was and he asked if I wanted to take part in this clinical trial. I said I did and they arranged for me to get this, the device. I just lucked out and was in the right place at the right time. Best move I ever made. Didn’t know anything about stem cells then, sure didn’t, I just knew I was miserable and if there was any way to make life better I just wanted to do it or try it.

And then I did this and it was like day and night.

Since I’ve done this my life has improved 100%. I can do a lot now that I couldn’t do before. My wife and I are so grateful that we can have this. Now we can go out to dinner and do anything we want. We could go out before but we had to always be careful because of the thing in my chest. But now I don’t even think about it. It’s like getting my life back.

I don’t notice it all. I don’t feel it at all. I hate to say it, but I can’t believe I’m on dialysis. I would like to have a kidney but I’ll be honest with you this is the next best thing.

When I go to the clinic there’s a lot of old people there and I just try to make them laugh, tell them jokes, I just can’t believe how good I feel and I want to make others feel good too.

I take the time to talk to them, and give them gum and that cheers them up. My wife has to keep me supplied with gum.

I’ve been married 45 years. We met in high school chorus. I didn’t care too much about singing but I went to chorus because I wanted to meet girls. That’s where I met Paula. Best move I ever made.

I sure don’t feel old. My wife and I are two people that love each other very dearly, that’s my blessing, with her help I couldn’t get old.

I’m a workaholic but until I got the Humacyte device I couldn’t work. I had to sell my business.

I used to be a private detective. It had its moments. My wife used to get mad because I got up at 2 or 3 in the morning to get someone who was in hiding. I had one guy, he was about 6’ 7”, big guy. I knocked at the door and said the name of the guy I was looking for, and asked if he was there. He asked why, so I told him why I was there and he said “It’s me,” and ran right over me and knocked me on the ground and ran away. But I managed to talk him into coming back.

We served a lot of papers on foreclosures and I hated that, and I would always try and help those people if I could.

One time I ran into an old lady, she was a nice woman, and her husband handled all the bills but he died and they had stock in Bernie Madoff’s company and when he went under it left her broke.  They had $1.7 million in a company that went bankrupt. She lost it all. She didn’t know what to do. When I went to serve her papers she hadn’t eaten in two days,  so I went and bought her and brought some groceries and made sure the electric bill got paid and then called her son and made sure she was taken care of.

My wife said we were going broke helping so many people, but I felt that if you help people it comes back to you and it has.

I volunteer at the VA, help out there when I can. Just trying to give back. Always have. I think if you can help someone you need to do it.

I feel damn lucky, really lucky, more ways than one. You have to understand I have lived 50 years longer than I should have; I could have died in Vietnam, so I would just say do not give up. Don’t give up. My wife wouldn’t let me give up, and things happen. If they are meant to be, of course. Something will happen and I’m telling you. The key is making people around you feel like they want to be around you.”

We are forever grateful to Frank for being willing to be part of a clinical trial that will, hopefully, improve the quality of life for many others. That is his legacy. Our thoughts and wishes go out to his wife Paula

Stories that caught our eye: new target for killing leukemia cancer stem cells and stem cell vesicles halt glaucoma

New stem cell target for acute myeloid leukemia (Karen Ring).  A new treatment for acute myeloid leukemia, a type of blood cancer that turns bone marrow stem cells cancerous, could be in the works in the form of a cancer stem cell destroying antibody.

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Acute Myeloid Leukemia (Credit: Medscape)

Scientists from the NYU Langone Medical Center and the Memorial Sloan Kettering Cancer Center identified a protein called CD99 that appears more abundantly on the surface of abnormal blood cancer stem cells compared to healthy blood stem cells. They developed an antibody that specifically recognizes and kills the CD99 wielding cancer stem cells while leaving the healthy blood stem cells unharmed.

The CD99 antibody was effective at killing human AML stem cells in a dish and in mice that were transplanted with the same type of cancer stem cells. Further studies revealed that the CD99 antibody when attached to the surface of cancer stem cells, sets off a cascade of enzyme activity that causes these cells to die. These findings suggest that cancer stem cells express more CD99 as a protective mechanism against cell death.

In an interview with Genetic Engineering and Biotechnology News, Chris Park, senior author on the Science Translational Medicine study, explained the importance of their work:

“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we also show that antibodies against this target can directly kill human AML stem cells. While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing.”

While this work is still in the early stages, Dr. Park stressed that his team is actively working to translate their CD99 antibody therapy into clinical trials.

“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials.”

 

Peculiar stem cell function may help treat blindness (Todd Dubnicoff). Scientists at the National Eye Institute (NEI) have uncovered a novel function that stem cells use to carry out their healing powers and it may lead to therapies for glaucoma, the leading cause of blindness in United States. Reporting this week in Stem Cells Translational Medicine, the researchers show that stem cells send out regenerative signals by shedding tiny vesicles called exosomes. Once thought to be merely a garbage disposal system, exosomes are now recognized as an important means of communication between cells. As they bud off from the cells, the exosomes carry proteins and genetic material that can be absorbed by other cells.

Microscopy image shows exosomes (green) surrounding retinal ganglion cells (orange and yellow). Credit: Ben Mead

Microscopy image shows exosomes (green) surrounding retinal ganglion cells (orange and yellow). Credit: Ben Mead

The researchers at NEI isolated exosomes from bone marrow stem cells and injected them into the eyes of rats with glaucoma symptoms. Without treatment, these animals lose about 90 percent of their retinal ganglion cells, the cells responsible for forming the optic nerve and for sending visual information to the brain. With the exosome treatment, the rats only lost a third of the retinal ganglion cells. The team determined that microRNAs – small genetic molecules that can inhibit gene activity – inside the exosome were responsible for the effect.

Exosomes have some big advantages over stem cells when comes to developing and manufacturing therapies which lead author Ben Mead explains in a press release picked up by Eureka Alert:

“Exosomes can be purified, stored and precisely dosed in ways that stem cells cannot.”

We’ll definitely keep our eyes on this development. If these glaucoma studies continue to look promising it stands to reason that there would be exosome applications in many other diseases.

Growing a rat pancreas in a mouse with stem cells & CRISPR: a solution for the organ shortage crisis?

Right now, about 120,000 Americans are on a waiting list for an organ transplant and 22 will die today before any organs become available. The plain truth is there aren’t enough organ donors to meet the demand. And according to the U.S. Department of Health and Human Services, the number of available organ donors has remained static over the past decade. How can we overcome this crisis?

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The need for organ transplants is growing but the number of donors is stagnant. Image: U.S. Dept. Human Health Services

One answer may be stem cells. These “blank slate” cells can specialize into virtually any cell type in the body which has many scientists pursuing the holy grail of stem cell research: creating an unlimited supply of human organs. Today, a team of Salk Institute scientists report in Cell that they’ve taken an early but important step toward that goal by showing it’s possible to grow rat organs within a mouse. The results bode well for not only organ transplants but also for the study of human development and disease.

Chimera – monster or medical marvel?
Our regular Stem Cellar readers will be familiar with several fascinating studies using stem cell-based 3D bioprinters or bioscaffolds which aim to one day enable the manufacturing of human tissues and organs. Instead of taking this engineering approach, the Salk team seeks a strategy in which chimeric animals are bred to grow human organs. The term “chimeric” is borrowed from Greek mythology that told tales of the chimera, a monster with a lion’s heads, a goat’s body and a serpent’s tail.

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The chimera of Greek Mythology: part lion, goat and snake. Image: Wikimedia Commons

The team’s first set of experiments explored the feasibility of this method by first focusing on rat-mouse chimeras. Reprogramming skin cells collected from rat tails, the scientists generated induced pluripotent stem cells (iPSCs) – cells with the embryonic stem cell-like ability to become any cell type – and injected them into very early stage mouse embryos. The embryos were then implanted into surrogate female mice and successfully carried to term. Examination of the resulting mouse pups showed that their tissues and organs contained a patchwork of both rat and mouse cells.

And for my next trick, I will make a rat pancreas in a mouse
Now, if the ultimate goal is to grow organs that are 100% human in a host animal, an organ that merely has a random patchwork human cells would miss the mark. To show there’s a way around this problem, the Salk team used the CRISPR gene-editing technique to generate mouse embryos that lacked a gene that’s critical for the development of the pancreas. Without the gene, no pancreas forms and the mice died shortly after birth. But when the rat iPSCs were integrated into the gene edited mice embryos, the rat cells picked up the slack as the embryo developed, resulting in chimeric mice with rat pancreases.

Using the same CRISPR gene editing strategy, the researchers also grew rat hearts, and if you can believe it, rat eyes in the chimeric mice. On top of that, the mice in these experiments were healthy with most reaching adulthood and one living two years, an elderly age for mice.

A first step toward growing patient-specific human organs in large animals
One small, actually big, problem is that mice are much too little to serve as chimeric hosts for human organs. So the team repeated these mixed species experiments in pigs which are much better matched to humans. In this case, they added human iPSCs to the pig embryos, implanted them into female pigs and let the embryos develop for four weeks. Although it wasn’t as efficient as the rat-mouse chimeras, the researchers did indeed observe human cells that had incorporated into the chimera and were showing the early signs of specializing in different cell types within the implanted pig embryos.

This work is the first time human iPSCs have been incorporated into large animal species (they also got it to work with cattle) and many years of lab work remain before this approach can help solves the organ shortage crisis. But the potential applications are spellbinding. Imagine a patient in need of an organ transplant: a small skin biopsy is collected to make iPSCs and, using this chimeric animal approach, a patient-derived organ could be grown.

Juan Carlos Izpisua Belmonte, the study’s team leader, talked about this possibility and more in a press release:

“Of course, the ultimate goal of chimeric research is to learn whether we can use stem-cell and gene-editing technologies to generate genetically-matched human tissues and organs, and we are very optimistic that continued work will lead to eventual success. But in the process we are gaining a better understanding of species evolution as well as human embryogenesis and disease that is difficult to get in other ways.”

Ethical concerns
Now, if the idea of breeding pigs or cows with human organs make you a little uneasy, you aren’t alone.  In fact, the National Institutes of Health announced in 2015 that they had halted funding research that introduces human stem cells into other animals. They want more time “to evaluate the state of the science in this area, the ethical issues that should be considered, and the relevant animal welfare concerns associated with these types of studies.”  To read more discussion on this topic, read this MIT Technology Review article from a year ago.