Investing in student researchers now for future stem cell therapy homeruns

Even though my San Francisco Giants didn’t make it to the World Series this year, I still watched Game 1 two nights ago between the Cleveland Indians and the Chicago Cubs. As each batter stepped up to the plate for their first at bat, I thought about all the years of training and in-game experience it must have required for each athlete to reach this pinnacle of their profession. That training certainly relied on mentoring from great coaches and early financial support in the form of athletic scholarships, etc. Without that help, you could argue that the number of young, high-caliber baseball players would dwindle over the generations and the sport eventually would lose relevance.


The CIRM Bridges Program: training the next generation of all-star stem cell researchers, like Eliana Ochoa-Bolton (pictured here)

I think the same can be said for stem cell research. The field is currently chock-full of veteran, superstar scientists who are leading the charge of bringing first-of-their-kind stem cell treatments to clinical trials (for example, check out Monday’s exciting blog). But the field is still in its infancy and will require a well-trained workforce of scientists, physicians and technicians throughout the 21st century and beyond to fully realize and implement the potential of stem cells to treat patients with unmet medical needs. But cuts in federal funding for research mean this is a particularly challenging time to get started on a scientific career, especially for economically disadvantaged students.

That’s where the Bridges to Stem Cell Research and Therapy Awards Program comes into the picture. Started in 2009, the program provides paid stem cell research internships to students at universities and colleges that don’t have major stem cell research programs. Each Bridges internship includes thorough hands-on training and education in stem cell research, and direct patient engagement and outreach activities that engage California’s diverse communities.

Earlier this year, the CIRM governing Board re-upped on their investment in the Bridges Program to the tune of $40 million. Each of the fourteen awarded schools will have enough funding to support up to ten trainees per year for up to five years. The program has become a source of pride for the CIRM team as well as for each campus. Case in point, this past Wednesday the news center at California State University, Northridge (CSUN) featured a story about the school’s new $2.77 million Bridges grant. Professor Cindy Malone, CSUN’s Bridges Program Director, looked back at the accomplishments from their previous round of funding which began in 2009:


Cindy Malone
CSUN biology professor

“When we first launched the [CSUN-UCLA Bridges to Stem Cell Research Program], we didn’t know how successful it would become. Our students are taking part in cutting-edge research alongside some of the greatest minds in stem cell research. They are presenting papers at some of the top professional conferences in the world. When they graduate, they are highly sought after by the top medical and graduate schools in the country, and rightly so.”


Eliana Ochoa-Bolton

One of those students is Eliana Ochoa-Bolton who spent much of her senior year at CSUN as a Bridges intern in the laboratory of Samantha Butler at UCLA. There, she contributed to the lab’s efforts to better understand the nerve signals that become damaged in spinal cord injury with the hope of eventually restoring them. Ochoa-Bolton, who is now a CSUN master’s student in biology and aspires to earn a doctorate, is very grateful for her Bridges experience: “It was such an amazing opportunity. I got to do work I didn’t think possible as an undergraduate.”

Now embarking on the second round of Bridges funding, Malone mapped out the plan for the program’s next five years:

“We will continue to partner with UCLA as our internship-host institution. There, our students will perform 10 months of intensive stem cell research. New research training courses will be launched in the next year to prepare our undergraduates for the new Stem Cell Scientist Training Program and for the increasingly technical job market in California.”

For us CIRM team members and the CIRM governing Board, the Bridges program and its high school counterpart, the CIRM Spark program, continue to be among our favorite awards because we’re continually amazed how much the student’s learn and we’re inspired by their unbounded enthusiasm for stem cell research.

It makes me very optimistic that these students are destined to hit some future stem cell treatments home runs.

A patient perspective on how stem cells could give a second vision to the blind

October is Blindness Awareness month. In honor of the patients who suffer from diseases of blindness and of the scientists and doctors who work tirelessly to develop treatments and cures for these diseases, we are featuring an interview with Kristin Macdonald, a woman who is challenged by Retinitis Pigmentosa (RP).

RP is a genetically inherited disease that affects the photoreceptors at the back of the eye in an area called the retina. It’s a hard disease to diagnose because the first signs are subtle. Patients slowly lose their peripheral vision and ability to see well at night. As the disease progresses, the window of sight narrows and patients experience “tunnel vision”. Eventually, they become totally blind. Currently, there is no treatment for RP, but stem cell research might offer a glimmer of hope.

Kristin MacDonald

Kristin MacDonald

Kristin Macdonald was the first patient treated in a CIRM-funded stem cell trial for RP run by Dr. Henry Klassen at UC Irvine. She is a patient advocate and inspirational speaker for the blind and visually impaired, and is also a patient ambassador for Americans for Cures. Kristin is an amazing woman who hasn’t let RP prevent her from living her life. It was my pleasure to interview her to learn more about her life’s vision, her experience in CIRM’s RP trial, and her thoughts on patient advocacy and the importance of stem cell research.

Q: Tell us about your experience with being diagnosed with RP?

I was officially diagnosed with RP at 31. RP is a very difficult thing to diagnose, and I had to go through a series of doctors before we figured it out. The signs were there in my mid-to-late twenties, but unfortunately I didn’t really know what they were.

Being diagnosed with RP was really surprising to me. I grew up riding horses and doing everything. I had 20/20 vision and didn’t need any reading glasses. I started getting these night vision symptoms in my mid-to-late 20s in New York when I was in Manhattan. It was then that I started tripping, falling and getting clumsy. But I didn’t know what was happening and I was having such a great time with my life that I just denied it. I didn’t want to acknowledge that anything was wrong.

So I moved out to Los Angeles to pursue an acting and television career, and I just kept ignoring that thing in the brain that says “something’s wrong”. By the time I broke my arm for the second time, I had to go to see a doctor. And that’s when they diagnosed me.

Q: How did you boost yourself back up after being diagnosed with RP?

RP doesn’t come with an instruction booklet. It’s a very gradual adjustment emotionally, physically and spiritually. The first thing I did was to get out of denial, which was a really scary place to be because you can break your leg that way. You have to acknowledge what’s happening in life otherwise you’ll never get anywhere or past anything. That was my first stage of getting over denial. As I slowly started to accept things, I learned to live in the moment, which in a way is a big thing in life because we should all be living for today.

I think the fear of someone telling you that you’re going to go into the dark when you’ve always lived your life in the light can be overwhelming at times. I used to go to the mall and sometimes a door to a store would be gone or an elevator that I used to see is gone. What I did to deal with these fears and changes was to become as proactive as possible. I enlisted all of the best people around me in the business. I started doing charitable work for the Center for the Partially Sighted and for the Foundation for Fighting Blindness. I sat on the board of, an internet radio service for the blind and visually impaired, where I still do my radio show. Through that, I met other people who were going through the same type of thing and would come into my home to teach me independent living skills.

I remember the first day when an independent living counselor from the Center for the Partially Sighted came to my house and said we have to check in and see what your adjustment to blindness is like. Those words cut through me. “Adjustment to blindness”. It felt like I was going to prison, that’s how it felt like to me back then. But I am so glad I reached out to the Center for the Partially Sighted because they gave me invaluable instructions on how to function as a blind person. They helped me realize I could really live a good life and be whole, and that blindness would never define me.

I also worked a lot on my spiritual side. I read a lot of positive thinking books and found comfort in my faith in god and the support from my family, friends and my boyfriend. I can’t even enumerate how good they’ve been to me.

Q: How has being blind impacted your ability to do the things you love?

I’m a very social person, so giving up my car and suddenly being confined at night was crushing to me. And we didn’t have Uber back then! During that time, I had to learn how to lead a full life socially. I still love to do salsa dancing but it’s tricky. If I stand on the sidelines, some of the dancers will pass you by because they don’t know you’re blind. I also learned how to horseback ride and swim in the ocean – just a different way. I go in the water on a surf leash. Or I ride around the ring with my best friend guiding me.

Kristin loves to ride horses.

Kristin doesn’t let being mostly blind stop her from riding horses.

Q: What treatments have you had for RP?

I investigated just about everything that was out there. [Laughs] After I was diagnosed, I became very proactive to find treatments. But after a while, I became discouraged because these treatments either didn’t work or still needed time for the FDA to give approval.

I did participate in a study nine years ago and had genetically modified cells put into my eye. I had two surgeries: one to put the cells in and one to take them out because the treatment hadn’t done anything. I didn’t get any improvement, and that was crushing to me because I had hoped and waited so long.

I just kept praying, waiting, reading and hoping. And then boom, all the sudden I got a phone call from UC Irvine saying they wanted me to participate in their stem cell trial for RP. They said I’d be the third person in the world to have it done and the first in their clinical trial. They told me I was to be the first North American patient to have progenitor cells put in my eye, which is pretty amazing.

Q: Was it easy to decide to participate in the UC Irvine CIRM-funded trial?

Yes. But don’t get me wrong, I’m human. I was a little scared. It’s a new thing and you have to sign papers saying that you understand that we don’t exactly know what the results will be. Essentially, you are agreeing to be a pathfinder.

Luckily, I have not had any adverse effects since the trial. But I’ve always had a great deal of faith in stem cells. For years, I’ve been hearing about it and I’ve always put my hopes in stem cells thinking that that’s going to be the answer for blindness.

Q: Have you seen any improvements in your sight since participating in this trial?

I was treated a year ago in June. The stem cell transplant was in my left eye, my worse eye that has never gotten better. It’s been about 15 months now, and I started to see improvement after about two months following the treatment. When I would go into my bathroom, I noticed that it was a lot brighter. I didn’t know if I was imagining things, but I called a friend and said, “I don’t know if I’m imagining things but I’m getting more light perception in this eye.”

Sure enough, over a period of about eight months, I had gradual improvement in light perception. Then I leveled off, but now there is no question that I’m photo sensitive. When I go out, I use my sunglasses, and I see a whole lot more light.

Because I was one of the first patients in the trial, they had to give me a small dose of cells to test for safety. So it was amazing that a smaller dose of cells was still able to help me gain back some sight! One of the improvements that I’ve had is that I can actually see the image of my finger waving back and forth on my left side, which I couldn’t before when I put mascara on. I say this because I have put lip pencil all over my mouth by accident. That must have been a real sight! For a woman, putting on makeup is really important.

Q: What was your experience like participating in the UC Irvine trial?

Dr. Klassen who runs the UC Irvine stem cell trial for RP is an amazing person. He was in the room with me during the transplant procedure. I have such a high regard and respect for Dr. Klassen because he’s been working on the cure for RP as long as I’ve had it. He’s someone who’s dedicated his life to trying to find an answer to a disease that I’ve been dealing with on a day-to-day basis.

Dr. Klassen had the opportunity to become a retinal surgeon and make much more money in a different area. But because it was too crushing to talk to patients and give them such a sad diagnosis, he decided he was going to do something about it. When I heard that, I just never forgot it. He’s a wonderful man and he’s really dedicated to this cause.

Q: How have you been an advocate for RP and blindness?

I’ve been an advocate for the visually impaired in many different aspects. I have raised money for different research foundations and donated my time as a host and an MC to various charities through radio shows. I’ve had a voice in the visually impaired community in one way or another on and off for 15 years.

I also started getting involved in Americans for Cures only a few months ago. I am helping them raise awareness about Proposition 71, which created CIRM, and the importance of funding stem cell research in the future.

I may in this lifetime get actual vision again, a real second vision. But in the meantime, I’ve been working on my higher self, which is good because a friend of mine who is totally blind reminded me today, “Kristin, just remember, don’t live for tomorrow just getting that eye sight back”. My friend was born blind. I told him he is absolutely right. I know I can lead a joyful life either way. But trust me, having a cure for RP would be the icing on the cake for me.

Q: Why is it important to be a patient advocate?

I think it’s so important from a number of different aspects, and I really felt this at the International Society for Stem Cell Research (ISSCR) conference in San Francisco this summer when certain people came to talk to me afterwards, especially researchers and scientists. They don’t get to see the perspective of the patient because they are on the other side of the fence.

I think it’s very important to be a patient advocate because when you have a personal story, it resonates with people much more than just reading about something or hearing about something on a ballot.  It’s really vital for the future. Everybody has somebody or knows somebody who had macular degeneration or became visually impaired. If they don’t, they need to be educated about it.

Q: Tell us about your Radio Show.

My radio show “Second Vision” is about personal development and reinventing yourself and your life’s vision when the first one fails. It was the first internet radio show to support the blind and visually impaired, so that’s why I’m passionate about it. I’ve had scores of authors on there over the years who’ve written amazing books about how to better yourself and personal stories from people who have overcome adversity from all different types of challenges in terms of emotional health, physical health or problems in their lives. You can find anything on the Second Vision website from interviews on Reiki and meditation to Erik Weihenmayer, the blind man who climbed the seven summits (the highest mountains of each of the seven continents).

Q: Why is stem cell research important?

I do think that stem cells will help people with blindness. I don’t know whether it will be a 100% treatment. Scientists may have to do something else along the way to perfect stem cell treatments whether it’s gene therapy or changing the number of cells or types of cells they inject into the eye. I really do have a huge amount of faith in stem cells. If they can regenerate other parts of the body, I think the eye will be no different.

To read more about Kristin Macdonald and her quest for a Second Vision, please visit her website.

Related Links:

How research on a rare disease turned into a faster way to make stem cells

Forest Gump. (Paramount Pictures)

Forest Gump. (Paramount Pictures)

If Forest Gump were a scientist, I’d like to think he would have said his iconic line a little differently. Dr. Gump would have said, “scientific research is like a box of chocolates – you never know what you’re gonna get.”

A new CIRM-funded study coming out of the Gladstone Institutes certainly proves this point. Published yesterday in the Proceedings of the National Academy of Sciences, the study found that a specific genetic mutation known to cause a rare disease called fibrodysplasia ossificans progressiva (FOP) makes it easier to reprogram adult skin cells into induced pluripotent stem cells (iPSCs).

Shinya Yamanaka received the Nobel Prize in medicine in 2012 for his seminal discovery of the iPSC technology, which enabled scientists to generate patient specific pluripotent stem cell lines from adult cells like skin and blood. These iPSC lines are useful for modeling disease in a dish, identifying new therapeutic drugs, and potentially for clinical applications in patients. However, one of the rate-limiting steps to this technology is the inefficient process of making iPSCs.

Yamanaka, a senior investigator at Gladstone, knows this problem all too well. In a Gladstone news release he commented, “inefficiency in creating iPSCs is a major roadblock toward applying this technology to biomedicine. Our study identified a surprising way to increase the number of iPSCs that we can generate.”

So how did Yamanaka and his colleagues discover this new trick for making iPSCs more efficiently? Originally, their intentions were to model a rare genetic disease called FOP. It’s commonly known as “stone man syndrome” because the disease converts normal muscle and connective tissue into bone either spontaneously or spurred by injury. Bone growth begins at a young age starting at the neck and progressively moving down the body. Because there is no treatment or cure, patients typically have a lifespan of only 40 years.

The Gladstone team wanted to understand this rare disease better by modeling it in a dish using iPSCs generated from patients with FOP. These patients had a genetic mutation in the ACVR1 gene, which plays an important role in the development of the embryo. FOP patients have a mutant form of ACVR1 that overstimulates this developmental pathway and boosts the activity of a protein called BMP (bone morphogenic protein). When BMP signaling is ramped up, they discovered that they could produce significantly more iPSCs from the skin cells of FOP patients compared to normal, healthy skin cells.

First author on the study, Yohei Hayashi, explained their hypothesis for why this mutation makes it easier to generate iPSCs:

“Originally, we wanted to establish a disease model for FOP that might help us understand how specific gene mutations affect bone formation. We were surprised to learn that cells from patients with FOP reprogrammed much more efficiently than cells from healthy patients. We think this may be because the same pathway that causes bone cells to proliferate also helps stem cells to regenerate.”

To be sure that enhanced BMP signaling caused by the ACVR1 mutation was the key to generating more iPSCs, they blocked this signal and discovered that much fewer iPSCs were made from FOP patient skin cells.

Senior Investigator Bruce Conklin, who was a co-author on this study, succinctly summarized the importance of their findings:

“This is the first reported case showing that a naturally occurring genetic mutation improves the efficiency of iPSC generation. Creating iPSCs from patient cells carrying genetic mutations is not only useful for disease modeling, but can also offer new insights into the reprogramming process.”

Gladstone investigators Bruce Conklin and Shinya Yamanaka. (Photo courtesy of Chris Goodfellow, Gladstone Institutes)

Gladstone investigators Bruce Conklin and Shinya Yamanaka. (Photo courtesy of Chris Goodfellow, Gladstone Institutes)

Ingenious CIRM-funded stem cell approach to treating ALS gets go-ahead to start clinical trial


Clive Svendsen

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, was first identified way back in 1869 but today, more than 150 years later, there are still no effective treatments for it. Now a project, funded by CIRM, has been given approval by the Food and Drug Administration (FDA) to start a clinical trial that could help change that.

Clive Svendsen and his team at Cedars-Sinai are about to start a clinical trial they hope will help slow down the progression of the disease. And they are doing it in a particularly ingenious way. More on that in a minute.

First, let’s start with ALS itself. It’s a particularly nasty, rapidly progressing disease that destroys motor neurons, those are the nerve cells in the brain and spinal cord that control movement. People with ALS lose the ability to speak, eat, move and finally, breathe. The average life expectancy after diagnosis is just 3 – 4 years. It’s considered an orphan disease because it affects only around 30,000 people in the US; but even with those relatively low numbers that means that every 90 minutes someone in the US is diagnosed with ALS, and every 90 minutes someone in the US dies of ALS.

Ingenious approach

In this clinical trial the patients will serve as their own control group. Previous studies have shown that the rate of deterioration of muscle movement in the legs of a person with ALS is the same for both legs. So Svendsen and his team will inject specially engineered stem cells into a portion of the spine that controls movement on just one side of the body. Neither the patient nor the physician will know which side has received the cells. This enables the researchers to determine if the treated leg is deteriorating at a slower rate than the untreated leg.

The stem cells being injected have been engineered to produce a protein called glial cell line derived neurotrophic factor (GDNF) that helps protect motor neurons. Svendsen and the team hope that by providing extra GDNF they’ll be able to protect the motor neurons and keep them alive.

Reaching a milestone

In a news release announcing the start of the trial, Svendsen admitted ALS is a tough disease to tackle:

“Any time you’re trying to treat an incurable disease, it is a long shot, but we believe the rationale behind our new approach is strong.”

Diane Winokur, the CIRM Board patient advocate for ALS, says this is truly a milestone:

“In the last few years, thanks to new technologies, increased interest, and CIRM support, we finally seem to be seeing some encouraging signs in the research into ALS. Dr. Svendsen has been at the forefront of this effort for the 20 years I have followed his work.  I commend him, Cedars-Sinai, and CIRM.  On behalf of those who have suffered through this cruel disease and their families and caregivers, I am filled with hope.”

You can read more about Clive Svendsen’s long journey to this moment here.


Stem cell stories that caught our eye: Blood stem cells on a diet, Bladder control after spinal cord injuries, new ALS insights

Putting blood stem cells on a diet. (Karen Ring)


Valine. Image: BMRB

Scientists from Stanford and the University of Tokyo have figured out a new way to potentially make bone marrow transplants more safe. Published yesterday in the journal Science, the teams discovered that removing an essential amino acid, called valine, from the diets of mice depleted their blood stem cells and made it easier for them to receive bone marrow transplants from other mice without the need for radiation or chemotherapy. Removing valine from human blood stem cells yielded similar results suggesting that this therapeutic approach could potentially change and improve the way that certain cancer patients are treated.

In an interview with Science Magazine, senior author Satoshi Yamazaki explained how current bone marrow transplants are toxic to patients and that an alternative, safer form of treatment is needed.

“Bone marrow transplantation is a toxic therapy. We have to do it to treat diseases that would otherwise be fatal, but the quality of life afterward is often not good. Relative to chemotherapy or radiation, the toxicity of a diet deficient in valine seems to be much, much lower. Mice that have been irradiated look terrible. They can’t have babies and live for less than a year. But mice given a diet deficient in valine can have babies and will live a normal life span after transplantation.”

The scientists found that the effects of a valine-deficient diet were mostly specific to blood stem cells in the mice, but also did affect hair stem cells and some T cells. The effects on these other populations of cells were not as dramatic however as the effects on blood stem cells.

Going forward, the teams are interested to find out whether valine deficiency will be a useful treatment for leukemia stem cells, which are stem cells that give rise to a type of blood cancer. As mentioned before, this alternative form of treatment would be very valuable for certain cancer patients in comparison to the current regimen of radiation treatment before bone marrow transplantation.

Easing pain and improving bladder control in spinal cord injury (Kevin McCormack)
When most people think of spinal cord injuries (SCI) they focus on the inability to walk. But for people with those injuries there are many other complications such as intense nerve or neuropathic pain, and inability to control their bladder. A CIRM-funded study from researchers at UCSF may help point at a new way of addressing those problems.

The study, published in the journal Cell Stem Cell, zeroed in on the loss in people with SCI of a particular amino acid called GABA, which acts as a neurotransmitter in the central nervous system and inhibits nerve transmission in the brain, calming nervous activity.

Here’s where we move into alphabet soup, but stick with me. Previous studies showed that using cells called inhibitory interneuron precursors from the medial ganglionic eminence (MGE) helped boost GABA signaling in the brain and spinal cord. So the researchers turned some human embryonic stem cells (hESCs) into MGEs and transplanted those into the spinal cords of mice with SCI.

Six months after transplantation those cells had integrated into the mice’s spinal cord, and the mice not only showed improved bladder function but they also seemed to have less pain.

Now, it’s a long way from mice to men, and there’s a lot of work that has to be done to ensure that this is safe to try in people, but the researchers conclude: “Our findings, therefore, may have implications for the treatment of chronically spinal cord-injured patients.”

CIRM-funded study reveals potential new ALS drug target (Todd Dubnicoff)
Of the many diseases CIRM-funded researchers are tackling, Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s Disease, has got to be one of the worst.


Motor neurons derived from skin cells of a healthy donor
Image: UC San Diego

This neurodegenerative disorder attacks and kills motor neurons, the nerve cells that control voluntary muscle movement. People diagnosed with ALS, gradually lose the ability to move their limbs, to swallow and even to breathe. The disease is always fatal and people usually die within 3 to 5 years after initial diagnosis. There’s no cure for ALS mainly because scientists are still struggling to fully understand what causes it.

Stem cell-derived “disease in a dish” experiments have recently provided many insights into the underlying biology of ALS. In these studies, skin cells from ALS patients are reprogrammed into an embryonic stem cell-like state called induced pluripotent stem cells (iPSCS). These iPS cells are grown in petri dishes and then specialized into motor neurons, allowing researchers to carefully look for any defects in the cells.

This week, a UC San Diego research team using this disease in a dish strategy reported they had uncovered a cellular process that goes haywire in ALS cells. The researchers generated motor neurons from iPS cells that had been derived from the skin samples of ALS patients with hereditary forms of the disease as well as samples from healthy donors. The team then compared the activity of thousands of genes between the ALS and healthy motor neurons. They found that a particular hereditary mutation doesn’t just impair a protein called hnRNP A2/B1, it actually gives the protein new toxic activities that kill off the motor neurons.

Fernando Martinez, the first author on this study in Neuron, told the UC San Diego Health newsroom that these news results reveal an important context for their on-going development of therapeutics that target proteins like hnRNP:

“These … therapies [targeting hnRNP] can eliminate toxic proteins and treat disease. But this strategy is only viable if the proteins have gained new toxic functions through mutation, as we found here for hnRNP A2/B1 in these ALS cases.”

Know Your Stem Cell History with Gladstone’s Interactive Timeline Tool

Stem cell biology is such a young area of research. It was only in 1998 that the first human embryonic stem cell line was generated by Jamie Thomson. A dizzying amount of breakthrough research has occurred in that short span of time, including the Nobel Prize winning work of Shinya Yamanaka for devising a method for reprogramming adult cells into an embryonic stem cell-like state (aka the induced pluripotent stem cell (iPS) cell technique). Because of the compressed time frame of these discoveries, it’s hard to keep track of the key highlights and the order in which they occurred. And there are plenty of fundamental, decades-old studies which our non-scientist stem cell champions may not be aware of.


The Gladstone’s stem cell timeline tool is fun and informative. Check it out!

That’s where the Gladstone Institutes’ new online stem cell timeline comes to the rescue. Released on October 12th, in celebration of Stem Cell Awareness Day, as well as the tenth anniversary of iPS cells, the timeline has a nifty interactive feature that allows you to swipe through a quick glance of the key milestones over the years. Then, simply tapping on a particular event gives you more detailed information. Check out it on the Gladstone Institutes website. Who knows, it might come in handy at your next pub trivia night or your next crossword puzzle.


Eggciting News: Scientists developed fertilized eggs from mouse stem cells

A really eggciting science story came out early this week that’s received a lot of attention. Scientists in Japan reported in the journal Nature that they’ve generated egg cells from mouse stem cells, and these eggs could be fertilized and developed into living, breathing mice.

This is the first time that scientists have reported the successful development of egg cells in the lab outside of an animal. Many implications emerge from this research like gaining a better understanding of human development, generating egg cells from other types of mammals and even helping infertile women become pregnant.

Making eggs from pluripotent stem cells

The egg cells, also known as oocytes, were generated from mouse embryonic stem cells and induced pluripotent stem cells derived from mouse skin cells in a culture dish. Both stem cell types are pluripotent, meaning that they can generate almost any cell type in the human body.

After generating the egg cells, the scientists fertilized the eggs through in vitro fertilization (IVF) using sperm from a healthy male mouse. They allowed the fertilized eggs to grow into two cell embryos which they then transplanted into female mice. 11 out of 316 embryos (or 3.5%) produced offspring, which were then able to reproduce after they matured into adults.


These mice were born from artificial eggs that were made from stem cells in a dish. (K. Hayashi, Kyushu University)

Not perfect science

While impressive, this study did identify major issues with its egg-making technique. First, less than 5% of the embryos made from the stem-cell derived eggs developed into viable mice. Second, the scientists discovered that some of their lab-grown eggs (~18%) had abnormal numbers of chromosomes – an event that can prevent an embryo from developing or can cause genetic disorders in offspring.

Lastly, to generate mature egg cells, the scientists had to add cells taken from mouse embryos in pregnant mice to the culture dish. These outside cells acted as a support environment that helped the egg cells mature and were essential for their development. The scientists are working around this issue by developing artificial reagents that could hopefully replace the need for these cells.

Egg cells made from embryonic stem cells in a dish. (K. Hayashi, Kyushu University)

Egg cells made from embryonic stem cells in a dish. (K. Hayashi, Kyushu University)

Will human eggs be next?

A big discovery such as this one immediately raises ethical questions and concerns about whether scientists will attempt to generate artificial human egg cells in a dish. Such technology would be extremely valuable to women who do not have eggs or have problems getting pregnant. However, in the wrong hands, a lot could go wrong with this technology including the creation of genetically abnormal embryos.

In a Nature news release, Azim Surani who is well known in this area of research, said that these ethical issues should be discussed now and include the general public. “This is the right time to involve the wider public in these discussions, long before and in case the procedure becomes feasible in humans.”

In an interview with , James Adjaye, another expert from Heinrich Heine University in Germany, raised the point that even if we did generate artificial human eggs, “the final and ultimate test for fully functional human ‘eggs in a dish’ would be the fertilization using IVF, which is also ethically not allowed.”

Looking forward, senior author on the Nature study, Katsuhiko Hayashi, predicted that in a decade, lab-grown “oocyte-like” human eggs will be available but probably not at a scale for fertility treatments. Because of the technical issues his study revealed, he commented, “It is too preliminary to use artificial oocytes in the clinic.”

Creating a “Pitching Machine” to speed up our delivery of stem cell treatments to patients


When baseball players are trying to improve their hitting they’ll use a pitching machine to help them fine tune their stroke. Having a device that delivers a ball at a consistent speed can help a batter be more consistent and effective in their swing, and hopefully get more hits.

That’s what we are hoping our new Translating and Accelerating Centers will do. We call these our “Pitching Machine”, because we hope they’ll help researchers be better prepared when they apply to the Food and Drug Administration (FDA) for approval to start a clinical trial, and be more efficient and effective in the way they set up and run that clinical trial once they get approval.

The CIRM Board approved the Accelerating Center earlier this summer. The $15 million award went to QuintilesIMS, a leading integrated information and technology-enabled healthcare service provider.

The Accelerating Center will provide key core services for researchers who have been given approval to run a clinical trial, including:

  • Regulatory support and management services
  • Clinical trial operations and management services
  • Data management, biostatistical and analytical services

The reason why these kinds of service are needed is simple, as Randy Mills, our President and CEO explained at the time:

“Many scientists are brilliant researchers but have little experience or expertise in navigating the regulatory process; this Accelerating Center means they don’t have to develop those skills; we provide them for them.”

The Translating Center is the second part of the “Pitching Machine”. That is due to go to our Board for a vote tomorrow. This is an innovative new center that will support the stem cell research, manufacturing, preclinical safety testing, and other activities needed to successfully apply to the FDA for approval to start a clinical trial.

The Translating Center will:

  • Provide consultation and guidance to researchers about the translational process for their stem cell product.
  • Initiate, plan, track, and coordinate activities necessary for preclinical Investigational New Drug (IND)-enabling development projects.
  • Conduct preclinical research activities, including pivotal pharmacology and toxicology studies.
  • Manufacture stem cell and gene modified stem cell products under the highest quality standards for use in preclinical and clinical studies.

The two centers will work together, helping researchers create a comprehensive development plan for every aspect of their project.

For the researchers this is important in giving them the support they need. For the FDA it could also be useful in ensuring that the applications they get from CIRM-funded projects are consistent, high quality and meet all their requirements.

We want to do everything we can to ensure that when a CIRM-funded therapy is ready to start a clinical trial that its application is more likely to be a hit with the FDA, and not to strike out.

Just as batting practice is crucial to improving performance in baseball, we are hoping our “Pitching Machine” will raise our game to the next level, and enable us to deliver some game-changing treatments to patients with unmet medical needs.


Trash talking and creating a stem cell community


Imilce Rodriguez-Fernandez likes to talk trash. No, really, she does. In her case it’s cellular trash, the kind that builds up in our cells and has to be removed to ensure the cells don’t become sick.

Imilce was one of several stem cell researchers who took part in a couple of public events over the weekend, on either side of San Francisco Bay, that served to span both a geographical and generational divide and create a common sense of community.

The first event was at the Buck Institute for Research on Aging in Marin County, near San Francisco. It was titled “Stem Cell Celebration” and that’s pretty much what it was. It featured some extraordinary young scientists from the Buck talking about the work they are doing in uncovering some of the connections between aging and chronic diseases, and coming up with solutions to stop or even reverse some of those changes.

One of those scientists was Imilce. She explained that just as it is important for people to get rid of their trash so they can have a clean, healthy home, so it is important for our cells to do the same. Cells that fail to get rid of their protein trash become sick, unhealthy and ultimately stop working.

Imilce is exploring the cellular janitorial services our bodies have developed to deal with trash, and trying to find ways to enhance them so they are more effective, particularly as we age and those janitorial services aren’t as efficient as they were in our youth.

Unlocking the secrets of premature aging

Chris Wiley, another postdoctoral researcher at the Buck, showed that some medications that are used to treat HIV may be life-saving on one level, preventing the onset of full-blown AIDS, but that those benefits come with a cost, namely premature aging. Chris said the impact of aging doesn’t just affect one cell or one part of the body, but ripples out affecting other cells and other parts of the body. By studying the impact those medications have on our bodies he’s hoping to find ways to maintain the benefits of those drugs, but get rid of the downside.

Creating a Community


Across the Bay, the U.C. Berkeley Student Society for Stem Cell Research held it’s 4th annual conference and the theme was “Culturing a Stem Cell Community.”

The list of speakers was a Who’s Who of CIRM-funded scientists from U.C. Davis’ Jan Nolta and Paul Knoepfler, to U.C. Irvine’s Henry Klassen and U.C. Berkeley’s David Schaffer. The talks ranged from progress in fighting blindness, to how advances in stem cell gene editing are cause for celebration, and concern.

What struck me most about both meetings was the age divide. At the Buck those presenting were young scientists, millennials; the audience was considerably older, baby boomers. At UC Berkeley it was the reverse; the presenters were experienced scientists of the baby boom generation, and the audience were keen young students representing the next generation of scientists.

Bridging the divide

But regardless of the age differences there was a shared sense of involvement, a feeling that regardless of which side of the audience we are on we all have something in common, we are all part of the stem cell community.

All communities have a story, something that helps bind them together and gives them a sense of common purpose. For the stem cell community there is not one single story, there are many. But while those stories all start from a different place, they end up with a common theme; inspiration, determination and hope.


Stem cell stories that caught our eye: relief for jaw pain, vitamins for iPSCs and Alzheimer’s insights

Jaw bone stem cells may offer relief for suffers of painful joint disorder
An estimated 10 million people in the US – mostly women –  suffer from problems with their temporomandibular joint (TMJ) which sits between the jaw bone and skull. TMJ disorders can lead to a number of symptoms such as intense pain in the jaw, face and head; difficulty swallowing and talking; and dizziness.

ds00355_im00012_mcdc7_tmj_jpgThe TMJ is made up of fibrocartilage which, when healthy, acts as a cushion to enable a person to move their jaw smoothly. But this cartilage doesn’t have the capacity to heal or regenerate so treatments including surgery and pain killers only mask the symptoms without fixing the underlying damage of the joint.

Reporting this week in Nature Communications, researchers at Columbia University’s College of Dental Medicine identified stem cells within the TMJ that can form cartilage and bone – in cell culture studies as well as in animals. The research team further showed that the signaling activity of a protein called Wnt leads to a reduction of these fibrocartilage stem cells (FSCSs) in animals and as a result causes deterioration of cartilage. But injecting a known inhibitor of Wnt into the animals’ damaged TMJ spurred growth and healing of the joint.

The team is now in search of other Wnt inhibitors that could be used in a clinical setting. In a university press release, Jeremy Mao, a co-author on the paper, talked about the implications of these results:

“They suggest that molecular signals that govern stem cells may have therapeutic applications for cartilage and bone regeneration. Cartilage and certain bone defects are notoriously difficult to heal.”

Take your vitamins: good advice for people and iPS cells
From a young age, we’re repeatedly told how getting enough vitamins each day is important for a healthy life. Our bodies don’t produce these naturally occurring chemicals but they carry out critical biochemical activities to keep our cells and organs functioning properly.


Carrots: a great source of vitamin A. Image source: Wikimedia Commons

Well, it turns out that vitamins are also an important ingredient in stem cell research labs. Results published the Proceedings of the National Academy of Sciences (PNAS) this week by scientists in the UK and New Zealand show that vitamin A and C work together synergistically to improve the efficiency of reprogramming adult cells, like skin or blood, into the embryonic stem cell-like state of induced pluripotent stem cells (iPSCs).

By the time a stem cell has specialized into, let’s say, a skin cell, only skin cell-specific genes are active while others genes, like those needed for liver function, are shut down. Those non-skin genes are silenced through the attachment of chemical tags on the DNA, a process called methylation. It essentially provides the DNA with the means of maintaining a skin cell “memory”. To convert a skin cell back into a stem cell-like state, researchers in the lab must erase this “memory” by adding factors which demethylate, or remove the methylation tags on the silenced, non-skin related genes.

In the current research picked up by Science Daily, the researchers found that both vitamin A and C increase demethylation but in different ways. The study showed that vitamin A acts to increase the production of proteins that are important for demethylation while vitamin C acts to enhance the enzymatic activity of demethylation.

These insights may help add to the growing knowledge on how to most efficiently reprogram adult cells into iPSCs. And they may prove useful for a better understanding of certain cancers which contain cells that are essentially reprogrammed into a stem cell-like state.

New angles for dealing with the tangles in the Alzheimer’s brain
The memory loss and overall degradation of brain function seen in people with Alzheimer’s Disease (AD) is thought to be caused by the accumulation of amyloid and tau proteins which form plaques and tangles in the brain. These abnormal structures are toxic to brain cells and ultimately lead to cell death.

But other studies of post-mortem AD brains suggest a malfunction in endocytosis – a process of taking up and transporting proteins to different parts of the cell – may also play a role. While follow up studies corroborated this initial observation, they didn’t look at endocytosis in nerve cells so it remained unclear how much of a role it played in AD.

In a CIRM-funded study published this week in Cell Reports, UC San Diego researchers made nerve cells from human iPSCs and used the popular CRISPR and TALEN gene editing techniques to generate mutations seen in inherited forms of AD. One of those inherited mutations is in the PS1 gene which has been shown to play a role in transporting amyloid proteins in nerve cells. The research confirmed that this mutation as well as a mutation in the amyloid precursor protein (APP) led to a breakdown in the proper trafficking of APP within the mutated nerve cells. In fact, they found an accumulation of APP in a wrong area of the nerve cell. However, blocking the action of a protein called secretase that normally processes the APP protein helped restore proper protein transport. In a university press release, team leader Larry Goldstein, explained the importance of these findings:


Larry Goldstein.
Image: UCSD

“Our results further illuminate the complex processes involved in the degradation and decline of neurons, which is, of course, the essential characteristic and cause of AD. But beyond that, they point to a new target and therapy for a condition that currently has no proven treatment or cure.”