10 Years of iPSCs

Midwest universities are making important tools to advance stem cell research

/ Pallavi Penumetcha / 1 Comment
580b4-ipscell

iPSCs are not just pretty, they’re also pretty remarkable

Two Midwest universities are making headlines for their contributions to stem cell research. Both are developing important tools to advance this field of study, but in two unique ways.

Scientists at the University of Michigan (UM), have compiled an impressive repository of disease-specific stem cell lines. Cell lines are crucial tools for scientists to study the mechanics of different diseases and allows them to do so without animal models. While animal models have important benefits, such as the ability to study a disease within the context of a living mammal, insights gained from such models can be difficult to translate to humans and many diseases do not even have good models to use.

The stem cell lines generated at the Reproductive Sciences Program at UM, are thanks to numerous individuals who donated extra embryos they did not use for in vitro fertilization (IVF). Researchers at UM then screened these embryos for abnormalities associated with different types of disease and generated some 36 different stem cell lines. These have been donated to the National Institute of Health’s (NIH) Human Embryonic Stem Cell Registry, and include cell lines for diseases such as cystic fibrosis, Huntington’s Disease and hemophilia.

Using one such cell line, Dr. Peter Todd at UM, found that the genetic abnormality associated with Fragile X Syndrome, a genetic mutation that results in developmental delays and learning disabilities, can be corrected by using a novel biological tool. Because Fragile X Syndrome does not have a good animal model, this stem cell line was critical for improving our understanding of this disease.

In the next state over, at the University of Wisconsin-Madison (UWM), researchers are doing similar work but using induced pluripotent stem cells (iPSCs) for their work.

The Human Stem Cell Gene Editing Service has proved to be an important resource in expediting research projects across campus. They use CRISPR-Cas9 technology (an efficient method to mutate or edit the DNA of any organism), to generate human stem cell lines that contain disease specific mutations. Researchers use these cell lines to determine how the mutation affects cells and/or how to correct the cellular abnormality the mutation causes. Unlike the work at UM, these stem cell lines are derived from iPSCs  which can be generated from easy to obtain human samples, such as skin cells.

The gene editing services at UWM have already proved to be so popular in their short existence that they are considering expanding to be able to accommodate off-campus requests. This highlights the extent to which both CRISPR technology and stem cell research are being used to answer important scientific questions to advance our understanding of disease.

CIRM also created an iPSC bank that researchers can use to study different diseases. The  Induced Pluripotent Stem Cell (iPSC) Repository is  the largest repository of its kind in the world and is used by researchers across the globe.

The iPSC Repository was created by CIRM to house a collection of stem cells from thousands of individuals, some healthy, but some with diseases such as heart, lung or liver disease, or disorders such as autism. The goal is for scientists to use these cells to better understand diseases and develop and test new therapies to combat them. This provides an unprecedented opportunity to study the cell types from patients that are affected in disease, but for which cells cannot otherwise be easily obtained in large quantities.

Stem Cell Experts Discuss the Ethical Implications of Translating iPSCs to the Clinic

/ Karen Ring / Leave a comment

Part of The Stem Cellar blog series on 10 years of iPSCs.

This year, scientists are celebrating the 10-year anniversary of Shinya Yamanaka’s Nobel Prize winning discovery of induced pluripotent stem cells (iPSCs). These are cells that are very similar biologically to embryonic stem cells and can develop into any cell in the body. iPSCs are very useful in scientific research for disease modeling, drug screening, and for potential cell therapy applications.

However, with any therapy that involves testing in human patients, there are ethical questions that scientists, companies, and policy makers must consider. Yesterday, a panel of stem cell and bioethics experts at the Cell Symposium 10 Years of iPSCs conference in Berkeley discussed the ethical issues surrounding the translation of iPSC research from the lab bench to clinical trials in patients.

The panel included Shinya Yamanaka (Gladstone Institutes), George Daley (Harvard University), Christine Mummery (Leiden University Medical Centre), Lorenz Studer (Memorial Sloan Kettering Cancer Center), Deepak Srivastava (Gladstone Institutes), and Bioethicist Hank Greely (Stanford University).

iPSC Ethics Panel

iPSC Ethics Panel at the 10 Years of iPSCs Conference

Below is a summary of what these experts had to say about questions ranging from the ethics of patient and donor consent, genetic modification of iPSCs, designer organs, and whether patients should pay to participate in clinical trials.

How should we address patient or donor consent regarding iPSC banking?

Multiple institutes including CIRM are developing iPSC banks that store thousands of patient-derived iPSC lines, which scientists can use to study disease and develop new therapies. These important cell lines wouldn’t exist without patients who consent to donate their cells or tissue. The first question posed to the panel was how to regulate the consent process.

Christine Mummery began by emphasizing that it’s essential that companies are able to license patient-derived iPSC lines so they don’t have to go back to the patient and inconvenience them by asking for additional samples to make new cell lines.

George Daley and Hank Greely discussed different options for improving the informed consent process. Daley mentioned that the International Society for Stem Cell Research (ISSCR) recently updated their informed consent guidelines and now provide adaptable informed consent templates that can be used for obtaining many type of materials for human stem cell research.  Daley also mentioned the move towards standardizing the informed consent process through a single video shared by multiple institutions.

Greely agreed that video could be a powerful way to connect with patients by using talented “explainers” to educate patients. But both Daley and Greely cautioned that it’s essential to make sure that patients understand what they are getting involved in when they donate their tissue.

Greely rounded up the conversation by reminding the audience that patients are giving the research field invaluable information so we should consider giving back in return. While we can’t and shouldn’t promise a cure, we can give back in other ways like recognizing the contributions of specific patients or disease communities.

Greely mentioned the resolution with Henrietta Lack’s family as a good example. For more than 60 years, scientists have used a cancer cell line called HeLa cells that were derived from the cervical cancer cells of a woman named Henrietta Lacks. Henrietta never gave consent for her cells to be used and her family had no clue that pieces of Henrietta were being studied around the world until years later.

In 2013, the NIH finally rectified this issue by requiring that researchers ask for permission to access Henrietta’s genomic data and to include the Lacks family in their publication acknowledgements.

Hank Greely, Stanford University

Hank Greely, Stanford University

“The Lacks family are quite proud and pleased that their mother, grandmother and great grandmother is being remembered, that they are consulted on various things,” said Hank Greely. “They aren’t making any direct money out of it but they are taking a great deal of pride in the recognition that their family is getting. I think that returning something to patients is a nice thing, and a human thing.”

What are the ethical issues surrounding genome editing of iPSCs?

The conversation quickly focused on the ongoing CRISPR patent battle between the Broad Institute, MIT and UC Berkeley. For those unfamiliar with the technique, CRISPR is a gene editing technology that allows you to cut and paste DNA at precise locations in the genome. CRISPR has many uses in research, but in the context of iPSCs, scientists are using CRISPR to remove disease-causing mutations in patient iPSCs.

George Daley expressed his worry about a potential fallout if the CRISPR battle goes a certain way. He commented, “It’s deeply concerning when such a fundamentally enabling platform technology could be restricted for future gene editing applications.”

The CRISPR patent battle began in 2012 and millions of dollars in legal fees have been spent since then. Hank Greely said that he can’t understand why the Institutes haven’t settled this case already as the costs will only continue to rise, but that it might not matter how the case turns out in the end:

“My guess is that this isn’t ultimately going to be important because people will quickly figure out ways to invent around the CRISPR/Cas9 technology. People have already done it around the Cas9 part and there will probably be ways to do the same thing for the CRISPR part.”

 Christine Mummery finished off with a final point about the potential risk of trying to correct disease causing mutations in patient iPSCs using CRISPR technology. She noted that it’s possible the correction may not lead to an improvement because of other disease-causing genetic mutations in the cells that the patient and their family are unaware of.

 Should patients or donors be paid for their cells and tissue?

Lorenz Studer said he would support patients being paid for donating samples as long as the payment is reasonable, the consent form is clear, and patients aren’t trying to make money off of the process.

Hank Greely said the big issue is with inducement and whether you are paying enough money to convince people to do something they shouldn’t or wouldn’t want to do. He said this issue comes up mainly around reproductive egg donation but not with obtaining simpler tissue samples like skin biopsies. Egg donors are given money because it’s an invasive procedure, but also because a political decision was made to compensate egg donors. Greely predicts the same thing is unlikely to happen with other cell and tissue types.

Christine Mummery’s opinion was that if a patient’s iPSCs are used by a drug company to produce new successful drugs, the patient should receive some form of compensation. But she said it’s hard to know how much to pay patients, and this question was left unanswered by the panel.

Should patients pay to participate in clinical trials?

George Daley said it’s hard to justify charging patients to participate in a Phase 1 clinical trial where the focus is on testing the safety of a therapy without any guarantee that there will be beneficial outcome to the patient. In this case, charging a patient money could raise their expectations and mislead them into thinking they will benefit from the treatment. It would also be unfair because only patients who can afford to pay would have access to trials. Ultimately, he concluded that making patients pay for an early stage trial would corrupt the informed consent process. However, he did say that there are certain, rare contexts that would be highly regulated where patients could pay to participate in trials in an ethical way.

Lorenz Studer said the issue is very challenging. He knows of patients who want to pay to be in trials for treatments they hope will work, but he also doesn’t think that patients should have to pay to be in early stage trials where their participation helps the progress of the therapy. He said the focus should be on enrolling the right patient groups in clinical trials and making sure patients are properly educated about the trial they are participating.

Thoughts on the ethics behind making designer organs from iPSCs?

Deepak Srivastava said that he thinks about this question all the time in reference to the heart:

Deepak Srivastava, Gladstone Institutes

Deepak Srivastava, Gladstone Institutes

“The heart is basically a pump. When we traditionally thought about whether we could make a human heart, we asked if we could make the same thing with the same shape and design. But in fact, that’s not necessarily the best design – it’s what evolution gave us. What we really need is a pump that’s electrically active. I think going forward, we should remove the constraint of the current design and just think about what would be the best functional structure to do it. But it is definitely messing with nature and what evolution has given us.”

Deepak also said that because every organ is different, different strategies should be used. In the case of the heart, it might be beneficial to convert existing heart tissue into beating heart cells using drugs rather than transplant iPSC-derived heart cells or tissue. For other organs like the pancreas, it is beneficial to transplant stem cell-derived cells. For diabetes, scientists have shown that injecting insulin secreting cells in multiple areas of the body is beneficial to Diabetes patients.

Hank Greely concluded that the big ethical issue of creating stem cell-derived organs is safety. “Biology isn’t the same as design,” Greely said. “It’s really, really complicated. When you put something into a biological organism, the chances that something odd will happen are extremely high. We have to be very careful to avoid making matters worse.”

For more on the 10 years of iPSCs conference, check out the #CSStemCell16 hashtag on twitter.

CIRM Grantees Reflect on Ten Years of iPS Cells

/ Todd Dubnicoff / Leave a comment

For the fourth entry for our “Ten Years of Induced Pluripotent Stem (iPS) Cells” series, which we’ve been posting all month, I reached out to three of our CIRM grantees to get their perspectives on the impact of iPSC technology on their research and the regenerative medicine field as a whole:

granteesStep back in time for us to August 2006 when the landmark Takahashi/Yamanaka Cell paper was published which described the successful reprogramming of adult skin cells into an embryonic stem cell-like state, a.k.a. induced pluripotent stem (iPS) cells. What do you remember about your initial reactions to the study?

Sheng Ding, MD, PhD
Senior Investigator, Gladstone Institute of Cardiovascular Disease
Shinya had talked about the (incomplete) iPS cell work well before his 2006 publication in several occasions, so seeing the paper was not a total surprise.

Alysson Muotri, PhD
Associate Professor, UCSD Dept. of Pediatrics/Cellular & Molecular Medicine
At that time, I was a postdoc. I was in a meeting when Shinya first presented his findings. I think he did not give the identity of the 4 factors at that time. I was very excited but remember hearing rumors in the corridors saying the data was too good to be true. Soon after, the publication come out and it was a lot of fun reading it.

Joseph Wu, MD, PhD
Director, Stanford Cardiovascular Institute
I remember walking to the parking lot after work. One of my colleagues called me on my cell phone and he asked if I had seen “the Cell paper” published earlier that day. I said I haven’t and I would look it up when I get back home. I read it that night and found it quite interesting because the concept was simple but yet powerful.

How soon after the publication did you start using the iPSC technique in your own research? At that time, what research questions were you able to start exploring that weren’t possible in the “pre-iPS” era?

Ding:
I think many of us in the (pluripotent stem cell) field quickly jumped on this seminal discovery and started working on the iPSC technology itself as, at the time, there were many aspects of the discovery that would need to be better understood and further improved for its applications.

Muotri:
Immediately after the first mouse Cell paper, but I started with human cells. There were some concerns if the 4 factors will also work in humans. Nonetheless, I start using the mouse cDNA factors in human cells and it worked! I was amazed to witness the transformation and see the iPSC colonies in my dish – I showed the results to everyone in the lab.

Soon after, the papers showing that the procedure worked in human cells were published but I already knew that. Thus, I started to apply this to model disease, my main focus. In 2010, we published the modeling of the first neurodevelopmental disease using the iPSC technology. It is still a landmark publication, and I am very happy to be among the pioneers who believed in the Yamanaka technology.

Wu:
We started working on iPS cells about a couple of months after the initial publication. To our surprise, it was incredibly easy to reproduce, and we were able to get successful clones after a few initial attempts, in part because we had already been working on human embryonic stem (ES) cells for several years.

I think the biggest advantage of iPS cells is that we can know the medical record of the donor. So we can study the correlation between the donor’s underlying genetic makeup and their resulting cellular and whole-body characteristics using iPS cells as a platform for integrating these analyses. Examining these correlations is simply not possible with ES cells since no adult donor exists.

Dr. Ding, what do you think made you and your research team especially skilled at pioneering the use of small molecules to replace the “Yamanaka” reprogramming factors?

Ding:
We had been working on identifying and using small molecules to modulate stem cell fate (including cell proliferation, differentiation, and reprogramming) before iPS cell technology was reported. So when the iPS cell work was reported, it was obvious to us that we could apply our expertise in small molecule discovery to better understand and improve iPS cell reprogramming and replace the genetic factors by pharmacological approaches.

Now, come back to the present and reflect on how the paper has impacted your research over the past 10 years. Describe some of the key findings your lab has made over the past 10 years through iPSC studies

Ding:
We’ve worked on three aspects that are related to iPS cell research: one is to identify small molecule drugs that can functionally replace the genetic reprogramming factors, and enhance reprogramming efficiency and iPS cell quality (to mitigate risks associated with genetic manipulation, to make the iPS cell generation process more robust and efficient, and reduce the cost etc).

Second is to better understand the reprogramming mechanisms, that would allow us to improve reprogramming and better utilize cellular reprogramming technology. For example, we had uncovered and characterized several fundamental mechanisms underlying the reprogramming process.

The third is to “repurpose/re-direct” the iPS cell reprogramming into directly generating tissue/organ-specific precursor cells without generating iPS cell (itself, which is tumorigenic and needs to be differentiated for most of its applications). This so-called “Cell-Activation and Signaling-Directed/CASD” reprogramming approach allowed us to directly generate cells in the brain, heart, pancreas, liver, and blood vessels.

Muotri:
My lab has focused on the use of iPS cells to model autism spectrum disorder, a condition that is very heterogeneous both clinically and genetically. Previous models for autism, such as animals and postmortem tissues, were limited because we could not have access to live neurons to test experimentally several hypotheses. Thus, the attractiveness of the iPS cell model, by capturing the genome of patients in pluripotent stem cells and then guide them to become neural networks.

While the modeling in a dish was a great potential, there were some clear limitations too: the variability in the system was too high for example. My lab has worked hard to develop a chemically-defined culture media (iDEAL) to grow iPS cells and reduce the variability in the system. Moreover, we have developed robust protocols to analyze the morphology and electrophysiological properties of cortical neurons derived from iPS cells. We have used these methods to learn more about how genes impact neuronal networks and to screen drugs for several diseases.

We also used these methods to create cerebral organoids or “mini-brains” in a dish and have applied this technology to test the impact of several genetic and environmental factors. For example, we recently showed that the Zika virus could target neural progenitor cells in these organoids, leading to defects in the human developing cortex. Without this technology, we would be limited to mouse models that do not recapitulate the microcephaly of the babies born in Brazil.

Wu:
Our lab has taken advantage of the iPS cell platform to better understand cardiovascular diseases and to advance the precision medicine initiative. For example, we have used iPS cells to elucidate the molecular mechanisms of diseases related to an enlarged heart, cardiac arrhythmias, viral- and chemotherapy-induced heart disease, the genetics of coronary artery disease, among other diseases. We have also used iPS cells for testing the safety and efficacy of various cardiovascular drugs (i.e., “clinical trial in a dish”).

How are your findings important in terms of accelerating stem cell treatments to patients with unmet medical needs?

Ding:
Better understanding the reprogramming process and developing small molecule drugs for enhancing reprogramming would allow more effective generation of safe stem cells with reduced cost for treating diseases or doing research.

Muotri:
We work with two concepts. First, we screen drugs that could repair the disorder at a cellular level in a dish, hoping these drugs will be useful for a large fraction of autistic individuals. This approach can also be used to stratify the autistic population, finding subgroups that are more responsive to a particular drug. This strategy should help future clinical trials.

In parallel, we also work with the idea of personalized medicine by using patient-derived cells to create “disease in a dish” models in the lab. We then examine the genomic information of these cells to help us find drugs that are more specific to that individual. This approach should allow us to better design the treatment, testing ideal drugs and dosage, before prescribing it to the patient.

Wu:
The iPS cell technology provides us with an unprecedented glimpse into cardiovascular developmental biology. With this knowledge, we should be able to better understand how cardiac and vascular cells regenerate in the heart during different phases of human life and also during times of stress such as in the case of a heart attack. However, to be able to translate this knowledge into clinical care for patients will take a significant amount of time. This is because we still need to tackle the issues of immunogenicity, tumorigenicity, and safety for products that are derived from ES and iPS cells. Equally importantly, we need to understand how transplanted cells integrate into the patient because based on our experience so far, most of the injected cells die upon transplant into the heart. Finally, the economics of this type of personalized regenerative medicine is a daunting challenge.

Finally, it’s foolhardy to predict the future but, just for fun, imagine that I revisit you in August 2026. What key iPSC-related accomplishments do you think your lab will achieve by then?

Ding:
We are hoping to have cell-based therapy and small molecule drugs developed based on iPS cell-related research for treating human diseases. Particularly, we are also hoping our cellular reprogramming research would lead us to identify and develop small molecule drugs that control tissue/organ regeneration in vivo [in an animal].

Muotri:
We hope to have improved several steps on the neural differentiation, dramatically reducing costs and increasing efficiency.

Wu:
We would like to use the iPS cell platform to discover several new drugs (or repurpose existing drugs) for our cardiovascular patients; to replace the current industry standard of drug toxicity testing using the hERG assay (which I believe is outdated); to predict what medications patients should be taking (i.e., precision cardiovascular medicine); and to elucidate risk index of genetic variants (in combination with genome editing approach).

Making a deposit in the Bank: using stem cells from children with rare diseases to find new treatments

/ Kevin McCormack / Leave a comment

Part of The Stem Cellar series on ten years of iPS cells

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For Chris Waters, the motivation behind her move from big pharmaceutical companies and biotech to starting a non-profit organization focused on rare diseases in children is simple: “What’s most important is empowering patient families and helping them accelerate research to the clinical solutions they so urgently need for their child ,” she says.

Chris is the founder of Rare Science. Their mission statement – Accelerating Cures for RARE Kids – bears a striking resemblance to ours here at CIRM, so creating a partnership between us just seemed to make sense. At least it did to Chris. And one thing you need to know about Chris, is that when she has an idea you should just get out of the way, because she is going to make it happen.

“The biggest gap in drug development is that we are not addressing the specific needs of children, especially those with rare diseases.  We need to focus on kids. They are our future. If it takes 14 years and $2 billion to get FDA approval for a new drug, how is that going to help the 35% of the 200 million children across the world that are dying before 5 years of age because they have a rare disease? That’s why we created Rare Science. How do we help kids right now, how do we help the families? How do we make change?”

Banking on CIRM for help

One of the changes she wanted to make was to add the blood and tissue samples from one of the rare disease patient communities she works with to the CIRM Induced Pluripotent Stem Cell Bank. This program is collecting samples from up to 3,000 Californians – some of them healthy, some suffering from diseases such as autism, Alzheimer’s, heart, lung and liver disease and blindness. The samples will be turned into iPS cells – pluripotent stem cells that have the ability to be turned into any other type of cell in the body – enabling researchers to study how the diseases progress, and hopefully leading to the development of new therapies.

 

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Lilly Grossman: photo courtesy LA Times

Chris says many kids with rare diseases can struggle for years to get an accurate diagnosis and even when they do get one there is often nothing available to help them. She says one San Diego teenager, Lilly Grossman, was originally diagnosed with Cerebral Palsy and it took years to identify that the real cause of her problems was a mutation in a gene called ADCY5, leading to abnormal involuntary movement. At first Lily’s family felt they were the only ones facing this problem. They have since started a patient family organization (ADCY5.org) that supports others with this condition.

“Even though we know that the affected individuals have the gene mutation, we have no idea how the gene causes the observable traits that are widely variable across the individuals we know.  We need research tools to help us understand the biology of ADCY5 and other rare disease – it is not enough to just know the gene mutation. We always wanted to do a stem cell line that would help us get at these biological questions.”

Getting creative

But with little money to spend Chris faced what, for an ordinary person, might have been a series of daunting obstacles. She needed consent forms so that everyone donating tissue, particularly the children, knew exactly what was involved in giving samples and how those samples would be used in research.  She also needed materials to collect the samples. In addition she needed to find doctors and sites around the world where the families were located to help with the sample collection.  All of this was going to cost money, which for any non-profit is always in short supply.

So she went to work herself, creating a Research Participant’s Bill of Rights – a list of the rights that anyone taking part in medical research has. She developed forms explaining to children, teenagers and parents what happens if they give skin or blood samples as part of medical research, telling them how an individual’s personal medical health history may be used in research studies. And then she turned to medical supply companies and got them to donate the tubes and other materials that would be needed to collect and preserve the tissue and blood samples.

Even though ADCY5 is a very rare condition, Chris has collected samples from 42 individuals representing 13 different families, some affected with the condition as well as their unaffected siblings and parents. These samples come from families all around the world, from the US and Europe, to Canada and Australia.

“With CIRM we can build stem cell lines. We can lower the barrier of access for researchers who want to utilize these valuable stem cell lines that they may not have the resources to generate themselves.  The cell lines, in the hands of researchers, can potentially accelerate understanding of the biology. They can help us identify targets to focus on for therapies. They can help us screen currently approved medications or drugs, so we have something now that could help these kids now, not 14 years from now.”

The samples Chris collects will be made available to researchers not just here in the US, but around the world. Chris hopes this program will serve as a model for other rare diseases, creating stem cell lines from them to help close the gap between discovery research and clinical impact.

Rare bears for rare disease

But in everything she does, in the end it always comes down to the patient families. Chris says so many children and families battling a rare disease feel they are alone. So she created with her team, the RARE Bear program to let them know they aren’t alone, that they are part of a worldwide community of support. She says each bear is handmade by the RARE Bear Army which spans 9 countries including 45 states in the US.  Each RARE Bear is different, because “they are all one of a kind bears for one of a kind kids. And that’s why we are here, to help rare kids one bear at a time.”  The RARE Bear program, also helps with rare disease awareness, patient outreach and rare disease community building which is key for RARE Science Research Programs.

It’s working. Chris recently got this series of photos and notes from the parents of a young girl in England, after they got their bear.

“I wanted to say a huge heartfelt thank you for my daughters Rare bear. It arrived today to Essex, England & as you can see from my pictures Isabella loves her already! We have named her Faith as a reminder to never give up!”

CIRM jumped on the iPS cell bandwagon before it had wheels

/ Don Gibbons / Leave a comment

Part of The Stem Cellar series on ten years of iPS cells

The first press release I issued that announced new research grants after arriving at CIRM in 2008 detailed 18 “New Cell Line” awards. Ten of those grants, announced in June that year, were for a type of stem cell that had not even been proven to exist until November the year before. Those induced pluripotent stem cells (iPS cells) so dramatically changed our field that their discovery led to the Nobel prize for Shinya Yamanaka just four years later.

Even though California voters approved the creation of CIRM in November 2004 and the agency’s first office opened just a few months later, the first grants for research projects did not get approved until February 2007. Litigation by opponents of stem cell research and the monumental task of setting up a granting agency from scratch resulted in a two-year gap between the vote and getting down to the business the voters resoundingly supported.

zack-ips-video

One of the first videos we placed on CIRMTV on YouTube was on iPSCs

Those first research grants sought to increase the sparse number of California researchers actually doing research with human embryonic stem cells. But just eight months later, in October 2007, CIRM staff had enough confidence in the mettle of California’s researchers that they went to our Board with a concept proposal for the New Cell Line awards that included the option of developing human iPS cells. While Yamanaka had first reprogrammed mouse skin cells to iPS cells in 2006, at the time of the Board presentation it was only speculated to be possible with human tissue. Not until the following month did he and Wisconsin’s James Thomson simultaneous publish the creation of human iPS cells, which CIRM staff annotated into the New Cell Line Request for Applications before they posted it in December 2007.

Former colleague Uta Grieshammer managed the New Cell Line awards as a CIRM senior science officer. In a recent interview she said the scientific questions posed by those grants showed the value of these awards.

 “The types of research we ended up funding under this call reflected the breadth of the questions important to embryonic stem cell and iPS cell work.”

Those projects included:

  • Creating early stage embryonic stem cells (ESCs), called ICM stage, which had been done in mice but not humans;
  • creating “clinical grade” ESCs fit for use in patients;
  • creating ESCs from embryos discarded by families at IVF clinics because they carried mutations for inherited diseases with the goal of developing better models for those diseases;
  • creating iPS cells from people with diseases, also to develop better models of disease;
  • ways to make iPS cells that did not result in the reprogramming factors being integrated into the cell’s genes permanently, which could render them unfit for human therapy;
  • looking to see if the age of the adult cell used to make iPS cells matters in the resulting stem cell;
  • comparing iPS and ESC lines to see if they are truly equivalent.

Those all turned out to be critical questions for the field, many still dominating much of the research today.  One of the most robust areas of iPS research involves creating disease-in-a-dish models using patient-derived stem cells for diseases that have been historically difficult to model in animals. One of the New Cell Line grantees, Fred Gage at the Salk Institute in San Diego, became one of the first researchers anywhere to report physiological differences between nerves grown from normal individuals versus nerves grown from patients with mental health conditions.

uta-grieshammer “The excitement to me personally with the result of our New Cell Lines is access to understanding complex genetic diseases through iPS cells,” said Uta, who currently is helping us untangle even more complex diseases as part of the management team for California’s personalized medicine initiative.

Gage, along with a co-investigator at Johns Hopkins, just last week received a $15 million grant from the National Institutes of Health to screen drug libraries against iPS cell-derived nerves to look for treatments for schizophrenia and bi-polar disorder. Clearly the CIRM team was onto something back in 2007.

Footnote:  This will be my last regular post for The Stem Cellar. I will be retiring from CIRM later this month, though I may heed the call if my colleagues ask me to do a guest post from my new base on Cape Cod.

Sneak Peak of our New Blog Series and the 10 Years of iPSCs Cell Symposium

/ Karen Ring / Leave a comment

New Blog Series

257c3-shinya_yamanaka

Shinya Yamanaka

A decade has passed since Dr. Shinya Yamanaka and his colleagues discovered the Nobel Prize-winning technology called induced pluripotent stem cells (iPSCs). These stem cells can be derived from adult tissue and can develop into any cell type in the body. They are an extremely useful tool to model disease in a dish, screen for new drug therapeutics, and have the potential to replace lost or damaged tissue in humans.

In honor of this amazing scientific discovery, we’re launching a new blog series about iPSCs and their impact on CIRM since we started funding stem cell research in 2007. It will be a four-part series over the course of September ending with a blog highlighting the 10 Years of iPSCs Cell Symposium that will be hosted in Berkeley, CA in late September.

Here are the topics:

  • CIRM jumps on the iPSC bandwagon before it had wheels.
  • Expanding the CIRM iPSC bank, how individuals are making a difference.
  • Spotlight on CIRM-funded iPSC research, interviews with CIRM-funded scientists.
  • What the experts have to say, recap of the 10 Years of iPSCs Cell Symposium.

A Conference Dedicated to 10 Years of iPSCs

slide-2Cell Press is hosting a Symposium on September 25th dedicated to the 10th anniversary of Yamanaka’s iPSC discovery. The symposium is featuring famous scientists in biology, medicine, and industry and is sure to be one of the best stem cell conferences this year. The speakers will cover topics from discovery research to technology development and clinical applications of iPSCs.

More details about the Symposium can be found here.

Here are a few of the talks and events we’re excited about:

  • Keynote by Gladstone’s Shinya Yamanaka: Recent progress in iPSC research and application
  • Panel on ethical considerations for clinical translation of iPSC research
  • Organized run with Shinya Yamanaka (I can finally say that I’ve run with a Nobel Prize winner!)
  • Advances in modeling ALS with iPSCs by Kevin Eggan, Harvard University
  • Cellular reprogramming approaches for cardiovascular disease by Deepak Srivastava, Director of the Roddenberry (named after Star Trek’s Gene Roddenberry) Stem Cell Center at the Gladstone Institutes in San Francisco
  • Keynote by MIT’s Rudolf Jaenisch: Stem cells, iPSCs and the study of human development and disease

CIRM will be attending and covering the conference through our blog and on Twitter (@CIRMnews).