CIRM-funded research leads to new treatment for forms of infertility, healthy child born

Human egg being nourished by a follicle. Image: Wellcome Images

Sometimes medical therapies arise in mysterious ways. Today, for example, one of our grantees at Stanford published a paper describing a new approach for treating some forms of infertility. So far one baby has been born using the technique.

The thing is that what he’d set out to do is generate new stem cell lines. How he got from one to the other is a serendipitous (and very happy) story.

The work was published September 30 in the Proceedings of the National Academy of Sciences.

Aaron Hsueh had gotten one of our SEED grants and then a Basic Biology grant to to produce mature eggs from ovaries that had been donated by women who had them removed for medical reasons, like cancer. He was trying to develop a source of eggs for somatic cell nuclear transfer (SCNT).

(SCNT is the technique that uses eggs and a cell from an adult to create new stem cell lines that are genetically identical to that adult. It is also used to create cloned animals, like Dolly the sheep. People had been concerned about where the eggs would come from for this technique, and Hsueh thought maybe these donated ovaries might be the answer.)

As part of his CIRM-funded work, Hsueh found some drugs that could help prompt the donated ovaries to produce mature eggs. Here’s how we describe the work in our press release:

The recent study also built on what researchers had long-known: that disrupting the ovary could promote follicle growth in some infertile patients. Hsueh worked out the molecular underpinnings of this phenomenon, finding a set of proteins that act as a brake in the ovary to restrain follicle growth. They found that cutting the ovary into smaller pieces could overcome this brake.

Hsueh and his colleagues at St. Mariana University School of Medicine in Japan thought that combining the two techniques—breaking up the ovary then activating follicles using the drugs Hsueh had discovered—might be an efficient way of producing eggs. They were right.

But here’s where the twist comes in. The team realized they could use their technique to generate eggs for SCNT, but it might also stimulate the production of eggs in women with certain forms of infertility.

Hsueh worked with some colleagues at St. Mariana University School of Medicine in Japan to put that idea to the test. The result: a baby boy. Another women is currently pregnant using the technique.

CIRM President Alan Trounson was a pioneering scientist in the development of in vitro fertilization, which has since produced more than five million children. He commented on Hsueh’s work:

“This is an important development for young infertile women who do not ovulate their own eggs and are unable to have children of their own. The fact that this discovery resulted from a CIRM Basic Biology Award shows the value in funding basic science. Removing the inhibition of primary germ cells to grow in the ovary is an important development for reproductive medicine. We never know what important advances will result from scientists probing fundamental aspects of stem cell biology.”

As for SCNT, Hsueh says that is no longer a focus of his lab. A team at Oregon Health & Science University succeeded in generating stem cell lines using SCNT last May (we wrote about that here). Hsueh is now hoping to improve his technique to make removing the woman’s ovary unnecessary.

Amy Adams

Not your father’s engineers – changing perceptions about engineering for a new generation

Dr. Rosa Canet-Aviles and Dr. Rahul Thakar talking about tissue engineering at the Exploratorium

The Golden Gate Bridge, the Taj Mahal and the Empire State Building are all beautiful, elegant structures. In a way they are works of art. They are also engineering marvels, designs that pushed the limits and skills of those who designed and built them.

So what do they have to do with stem cells? Well, some of the most exciting and, in its own way, pioneering work in engineering these days is taking place on a much smaller scale than those buildings, inside the human body, using tissue engineering to create new body parts such as a nose or windpipe, and one day even create new organs such as a heart or liver.

On Sunday September 29th, the Exploratorium – a world class science museum in San Francisco – held its annual Engineering Day, where they opened their doors and invited people to come in, for free, and learn all about the different forms that engineering takes. The goal of the day is to change perceptions about engineering, to help young people appreciate the sheer variety of areas it covers, and to get them to consider it as a career option.

Two of the stem cell agency’s Science Officers, Dr. Rosa Canet-Aviles and Dr. Rahul Thakar, took on the challenge of getting people to think about engineering in a different way, to understand that creating new structures inside the body was just as exciting, and in it’s own way even more amazing than building magnificent temples or bridges.

Rosa gave a quick overview of what stem cells are, how they work and what they can do. Rahul followed up with a look at how we are using them to change the way we treat disease and to build entirely new body parts. Oh, and they did this in both English and Spanish (Rahul in English and Rosa in Spanish) as the event was designed to encourage more young Latinos to enter engineering.

It’s always fun to watch an audience as they realize that what they are looking at is a medical marvel, a man-made body part that looks and functions like the real thing. It awakens them to the potential of this work – and Rosa and Rahul were quick to point out that right now it’s still just potential, that we have a long way to go before we can create functioning organs.

Some of our CIRM funded researchers are working hard to make that day a reality. Dr. Mark Humayun at the University of Southern California is working on creating a kind of scaffold to make sheets of cells found in the eye that can then be used to treat macular degeneration, the leading cause of vision loss in adults. You can read about his work here. Dr. Traci Grickscheit at Children’s Hospital of Los Angeles is working on creating tissue-engineered intestines to replace those damaged by disease. Her work can be found here and here. Also, Dr. Grickscheit along with other CIRM grantees are featured in our video summary of a CIRM-sponsored Tissue Engineering Workshop held in 2012:

Kevin McCormack

Stem cell stories that caught our eye: chemical weapons, Parkinson’s Disease and Cancer

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Artillery shells containing mustard gas

Organs on a chip for chemical weapons testing. Chemical weapons are in the news right now a little too much for my taste, but I was glad to see stem cell research is contributing to finding potential treatments for these unthinkable agents. The U.S. Army Edgewood Chemical Biological Center is the only facility in the U.S. allowed to produce chemical warfare agents for research purposes, to understand how those agents affect the body and to explore treatment options. Working with three universities the researchers there use reprogrammed stem cells, iPS cells, to grow the tissues of specific organs. Up first are heart, liver and lung. They grow them on thumb drive-size chips that have micro fluidic channels to mimic blood vessels that allow the tissue to grow in multiple layers and better mimic the real organ tissue. They will be testing various potential treatments on each type of organ. The work was described on the R&D news website.

Reprogrammed stem cells safe in primates in Parkinson’s test. Many researchers hold out great hope that we will be able to take skin or other adult cells from a patient and turn then into the desired tissue needed for repair, say nerve cells, and not have them rejected by the patient’s immune system. But some studies over the past two years have suggested that although these new cells contain the same genes as the patient, they might still cause an immune response. New data from Japan suggests that this may not be a concern. They took cells from monkey’s mouths or blood, reprogrammed them to be iPS type stem cells, and then matured them into neurons capable of producing dopamine, the protein that is in short supply in Parkinson’s disease.

Each monkey got six injections of their own reprogrammed cells into the area of the brain where that type of neuron normally resides. Over the course of several months the team saw very little immune response and even when there was some response, the nerve cells survived. This holds out hope iPS cells could become a therapy for the disease. The work was discussed in the Discover magazine blog today. You can read more about the Parkinson’s disease research CIRM funds on our website.

Therapy target found in brain cancer stem cells. A CIRM-funded researcher at the Sanford-Burnham Medical Research Institute in La Jolla has found that cancer stem cells that are part of a certain type of brain cancer use two very specific enzymes to speed up the rate that they divide. The research team also found drugs that were able to block the action of those enzymes. They showed that these drugs could block the growth of mouse tumors as well as the growth of human tumors that had been transplanted into mice. Robert Wechsler-Reya, who holds a CIRM Leadership award, led the work that was described in Drug Discovery & Development today. This video has more detailed information about cancer stem cells.

New York Times Op/Ed on R&D budget cuts. Regular New York Times Opinion Page contributor Thomas Friedman frequently writes about the importance of science and engineering in keeping our country competitive on a world stage. This week he lamented the impact of the sequestration budget cuts on the National Institutes of Health. He quotes NIH Director Francis Collins saying that this coming year the agency will not be able to fund 640 projects that scored in the top 17 percent of all proposals. And of those, 150 were from teams that had prior grants, had shown they were onto something, and would now be cut off. Collins said, “So you damage the previous investment as well as the future one.”

Friedman’s column was a call to not waste our great potential. He wrote: “In a world where the big divide is no longer between developed and developing countries but rather between high-imagination-enabling countries and low-imagination-enabling countries, we remain the highest-imagination-enabling country in the world.” He clearly fears that our nation is squandering a tremendous advantage. I agree.

Don Gibbons

Introducing a new series of animated stem cell videos – StemCellShorts

This post was originally published by the Canadian Stem Cell Network’s Signals blog

Welcome to the official launch of the first StemCellShorts video: “What is a stem cell?” narrated by stem cell research great Dr. Jim Till. Join us again on October 11 and 25 for the online premieres of two more videos in the series.

Anyone who has spent time searching the Internet for quality educational materials will no doubt have encountered these common problems: there’s loads of stuff out there; not all of it is particularly good, current or accurate; the format and length may not be appropriate; and it may have a different focus than what you’re looking for (i.e. has commercial interests or is targeted at a narrow audience).

This is certainly true of online information pertaining to stem cell science, so when the Stem Cell Network offered a Public Outreach Award to help create educational or lay-friendly resources for public consumption, a colleague, Mike Long and I embarked on the creation of StemCellShorts.

StemCellShorts is a series of animated videos, roughly one-minute in length, that answers basic questions about stem cell research. Important to the success and academic credibility of the pieces, we decided to have each piece narrated by a prominent Canadian stem cell researcher. We are proud to launch the first video today, focusing on answering the questions “What is a stem cell?”. The piece is narrated by, arguably the most famous Canadian stem cell researcher, Dr. Jim Till.

Dr. Till had this to say about the project, “I felt that it was important to contribute to “What is a stem cell” because of the fortuitous involvement of Dr. Ernest McCulloch and myself in what turned out to be the foundation of a new field of experimental stem cell research. I also hoped that my participation might possibly increase, to some extent, interest in the video.” – Dr. Jim Till, Professor Emeritus, Medical Biophysics, University of Toronto

Two more videos, “What are embryonic stem cells?” narrated by Dr. Janet Rossant, and “What are induced pluripotent stem cells?” narrated by Dr. Mick Bhatia will be released on October 11th and 25th (respectively) and will be screened at the Till & McCulloch Meetings in Banff on October 24. We are also happy to announce that we have received a second round of funding from the Stem Cell Network that is being matched by the Canadian Stem Cell Foundation as a partner. These funds will be used to create an additional five videos in a similar style and format as the initial three, and are scheduled to be released in 2014.

Ben Paylor

Best of the blog: Progress in Alzheimer’s disease research

More than 5 million people in the country suffer from Alzheimer’s disease and doctors estimate that about half to three-quarters of all dementia patients have Alzheimer’s.

On this blog we often write about how our grantees are progressing toward a therapy for the disease, but we wanted to pull the best of those posts into one place. Here are some of the most interesting posts if you want to learn the latest about Alzheimer’s disease and research by CIRM grantees.

1. New Alzheimer’s Ask the Expert video: Of stem cells, iphones and a cellular black box 

2. Who’s the boss of the brain? How stem cells repair damage

3. Lawrence Goldstein discusses Alzheimer’s & ALS research, need for more funding

4. Defective garbage disposal cells in brain may explain Alzheimer’s tol

5. Alzheimer’s disease could be helped by a type of brain cell recently generated from embryonic stem cells

6. Understanding Alzheimer’s by watching errant neuron proteins in real-time 

7. Alzheimer’s disease in a dish provides hope, avenue to therapies

8. National war on Alzheimer’s disease brings hope to patients and caregivers 

For a complete list of Alzheimer’s disease research we’ve funded, see the Alzheimer’s fact sheet on our website.

Rina Shaikh-Lesko

Through their lens: stem cells, schizophrenia, and conversation

This summer we’re sponsoring high school interns in stem cell labs throughout California. We asked those students to contribute to our Instagram photos and YouTube videos about life in the lab, and write about their experiences.

In addition to carrying out a stem cell research project, the students were expected to carry out a secondary project relating their work to other areas of study.

Christina Tebbe using a microtome to cut extremely thin slices of brain tissue.
She submitted this photo to our #CIRMStemCellLab Instagram feed

For my second project, I have chosen to relate my knowledge of stem cells towards the topic of effective and ineffective communication between romantic partners under stressful circumstances.

The overall aspect of this project was to observe the verbal and nonverbal mimicry that two partners may appear to be doing, and the reasons towards why these mimicries may happen. There are two key types of mimicry that this study analyzed which included; behavioral mimicry, examples of this include touching or movement, and verbal mimicry, examples for this include speech or writing patterns. Previous research has indicated how mimicry comes about more often when one is engaging with someone that they know well or have had some sort of close-knit relationship with.

We may have this preconceived notion of how people who have a more close relationship with one another will be the ones who unconsciously mimic each other in every aspect due to their knowledge of how the other one acts. To us, this may seem like the logical reasoning, but this study’s results indicated how subjects who in fact reported more closeness to their partners showed lower instances of mimicry overall, especially under stressful circumstances. From this outcome, which is opposite to what one may have previously thought, a certain question gets brought up and that is of the role of mimicry in stressful conversations.

In terms of stem cells, my primary project dealt with the effects of ablating neural stem cells and restraint stress on behaviors relevant to animal models neuropsychiatric diseases, in specific, schizophrenia. My first thoughts in relating stem cells to this second project has to do with a person’s behavior and how it would possibly be altered if we were to ablate their neural stem cells, and how this would effect them mimicking their partner. While it has been indicated on animals how ablating the neural stem cell system alone has been shown no to effect behavior, we then add a stress component to that, and see if this produces any alterations. In terms of mimicry we see how when a person is exhibiting a great amount of stress the perceiver may unconsciously lower their amount of mimicry due to the fact that if they were to mimic the person it may negatively influence the conversation and create an awkward tension throughout the rest of the conversation. Having a person subjected to stress in general can cause their neural stem cell count to become ablated, thus altering how they may behave. I imagine that if we were to ablate person’s stem cells that if they were in a social situation and assuming that they are the perceiver, they would have zero to no mimicry with the other partner.

Christina Tebbe

Christina submitted these videos about her experience:

Two CIRM grantees collaborate with novel technologies to halt Huntington’s

Brain volume is reduced in people with Huntington’s disease. Image: Frank Gaillard, Wikimedia commons

The deadly neurodegenerative condition Huntington’s disease occurs in people with a mutation in a gene called huntingtin. Scientists have known that since 1993.

The question has been what to do about it. There is currently no therapy to slow or halt the inevitable degeneration of people with the mutation.

Steven Finkbeiner at the Gladstone Institutes recently got a Basic Biology award to better understand what goes wrong in the neurons of people who carry that mutated huntingtin gene. Bernadette Tansey recently wrote in Xconomy about his work and his collaboration with San Bruno-based Numerate, which got one of our Early Translational Awards to find drugs that block whatever is that’s going wrong in those cells.

Tansey described the relationship like this:

Finkbeiner figured out how a region of a mutant protein attacks the nerves of people with Huntington’s, a devastating neurodegenerative disorder that leads to disability and eventual death. Numerate will be looking for drug candidates to block that protein.

She goes on:

Numerate will be searching for a small molecule that prevents the mutant huntingtin protein from folding into a particular structure that, according to Finkbeiner’s research, helps it destroy nerve cells. Once Numerate has identified its best bets, Finkbeiner’s lab will use a second new method that may also revolutionize drug discovery. His lab will first test the drug candidates on human nerve cells grown in a lab dish, rather than in animals that have been engineered to develop a facsimile of Huntington’s disease in humans.

The key point here is that they are going to be testing the drugs in human cells that contain the mutated gene. This is a dramatic difference from older approaches which relied on animals with a facsimile of the disease. The animals don’t have the same disease, the animals aren’t human, and the drugs found to be effective in that system in the past haven’t worked in people.

This is one of a few novel approaches were funding to find a therapy for Huntington’s disease. You can read about the rest, and watch our videos about those approaches, on our Huntington’s disease fact sheet.

Amy Adams

Through their lens: Charlotte Hayward on why young people should learn about stem cells and computation

This summer we’re sponsoring high school interns in stem cell labs throughout California. We asked those students to contribute to our Instagram photos and YouTube videos about life in the lab, and write about their experiences.

In addition to carrying out a stem cell research project, the students were expected to carry out a secondary project relating their work to other areas of study.

Charlotte Hayward submitted this photo to our #CIRMStemCellLab Instagram feed. She did a stem cell research internship this summer in the laboratory of Tod Kippin at University of California, Santa Barbara.

For my second project I have chosen to relate my knowledge of stem cells to computer science. In today’s advanced technological world, teaching the next generation how to use computers in the most effective way is important. For this purpose Patrick Kim, under the supervision of his mentor, Bryce Boe, is attempting to create a curriculum to efficiently teach elementary school age children computational thinking. Essentially, the project aims to teach kids to think more like a computer. They have chosen to do this through a computer program that allows the children to visually see the steps of computer programming while they attempt to program a certain criteria of commands. They have also developed a system by which a teacher with little to no knowledge of computational thinking can grade and correct a student’s work.

Stem cells could be integrated into this project in a very simple yet logically necessary way. In the same way that one could argue computer science is the future of educational technology, someone could just as easily argue that stem cells are the future of biological research. The potential of both computers and stem cells have only barely been discovered, and in my lifetime I expect to see dramatic leaps in the capability of both of these topics. So, I would like to propose an integrated computational thinking and stem cells curriculum.

In a program much like the one being developed currently, I would like to simultaneously teach kids to intricate biology of stem cells as well as the process of computer programming. I would do this by having the children perform the steps of computer science, such as a sequence of processes done in order to complete a processing task, while having each of the steps be labeled a biological step of the stem cell field, such as cell differentiation. For example, a child would sequence the steps of cell differentiation in the format necessary to be considered computational thinking. In this way the children would be discretely learning a new and more modern way of thinking while still learning a modern and important biological lesson.

It is extremely important to educate our youth, and I have profound respect to all who dedicate their lives to it. One problem we see in today’s society is an inadequate education. This may partly be due to the fact that we are not re evaluating the skills that this generation needs to learn. Of course history and art are extraordinarily important, but unlike 20 years ago, regenerative medicine and computer science are paramount skills. Both biology and computer science are very logical and systematic which make them compatible to integrate into one curriculum.

Charlotte Hayward

Charlotte sent us this video of her experience:

Funding young scientists key to future therapies: investor creates endowment to support UCSF graduate students

It’s nice to see our sentiments expressed by someone as influential as Michael Moritz, a venture capital investor who previously supported successes like Google and PayPal. Like us, he thinks it’s important to fund future scientists as well as the research itself.

University of California, San Francisco just announced a $30 million gift from Moriz and his wife Harriet Heyman to support PhD students in basic sciences at UCSF. Their announcement quoted UCSF Chancellor Susan Desmond-Hellmann.

“With the freedom to work in multiple labs and across disciplines, they make discoveries at the intersections of research, fostering collaborations as unlikely as they are productive,” she said. “Many of these students work in the labs that are exploring new approaches to understanding cancer, diabetes, cardiovascular disease and more. Their novel perspectives and unbridled curiosity give rise to powerful questions that can alter a lab’s entire course of research. We are deeply grateful to Michael and Harriet for this gift.”

Ron Leuty of the San Francisco Business Times interviewed Moritz about the gift. Leuty asked Moritz whether the gift will also help the primary investigators running the labs:

The problems have been much more acute in recent years. The pinch has already been felt. The cutbacks have been made. The admission rates of students have been cut back. This will restore things, at least with Ph.D.s, to where they were so studies can go on unabated. And, hopefully, the medical and scientific breakthroughs at UCSF will continue.

Our first round of funding back in 2006 supported graduate training programs in stem cell research at institutions throughout California. Since then, we’ve funded another round of graduate training programs, a training program for undergraduate and masters students and another for high school students.

These students are the future of stem cell research. They will be the lab technicians in companies developing stem cell therapies and they will become the primary researchers, developing the next generation of stem cell therapies. Given all that, we think it’s important to be supporting the best and brightest young scientists.

Amy Adams

Testing a therapy for Duchenne muscular dystrophy in patient stem cells

Human chromosomes showing location of dystrophin gene. Credit: Wessex Reg. Genetics Centre. Wellcome Images

The New York Times has a detailed story today about an experimental therapy for the devastating childhood disease Duchenne muscular dystrophy. The Times story describes the effects of muscular dystrophy:

Duchenne, which affects as many as 15,000 Americans, mainly boys, is the most severe common form of muscular dystrophy, the focus of those Jerry Lewis telethons. There is no good treatment, though steroids help. Boys with Duchenne are typically in wheelchairs by their early teenage years and die from cardiac or respiratory failure in their 20s.

The drugs in development use a technique called exon skipping to essentially trick the cell’s machinery into misreading a genetic mutation. Instead of producing the defective protein responsible for the disease, those cells produce a more functional version of that protein. (Here’s a clever video depicting the process.) Or at least that’s what happens in the lab.  

The problem is that aside from some very compelling anecdotes, it’s not clear how effective the drugs are in people. Trials are still underway, and additional drugs with a related but different function are also in development so it will be a number of years before the verdict is in on this approach.

We’ve funded one of the related approaches in an award to Stanley Nelson at UCLA. There’s a description of his approach to treating muscular dystrophy on our website. He is testing an exon-skipping drug combined with another drug to see if the combination is more effective than the single drug alone.

Nelson and his wife, fellow scientist Carrie Miceli, are testing the drugs in a lab dish using muscle cells derived from stem cells of people with muscular dystrophy. These cells contain the mutation that causes muscular dystrophy and, the team hopes, accurately reflects how human cells would react to their combination of drugs.

The pair describe their approach in this short video:

Our website has a list of all awards we’ve funded that target muscular dystrophy

Amy Adams