Stem cells reveal developmental defects in Huntington’s disease

Three letters, C-A-G, can make the difference between being healthy and having a genetic brain disorder called Huntington’s disease (HD). HD is a progressive neurodegenerative disease that affects movement, cognition and personality. Currently more than 30,000 Americans have HD and there is no cure or treatment to stop the disease from progressing.

A genetic mutation in the huntingtin gene. caused by an expanded repeat of CAG nucleotides, the building blocks of DNA that make our genes, is responsible for causing HD. Normal people have less than 26 CAG repeats while those with 40 or more repeats will get HD. The reasons are still unknown why this trinucleotide expansion causes the disease, but scientists hypothesize that the extra CAG copies in the huntingtin gene produce a mutant version of the Huntingtin protein, one that doesn’t function the way the normal protein should.

The HD mutation causes neurodegeneration.

As with many diseases, things start to go wrong in the body long before symptoms of the disease reveal themselves. This is the case for HD, where symptoms typically manifest in patients between the ages of 30 and 50 but problems at the molecular and cellular level occur decades before. Because of this, scientists are generating new models of HD to unravel the mechanisms that cause this disease early on in development.

Induced pluripotent stem cells (iPSCs) derived from HD patients with expanded CAG repeats are an example of a cell-based model that scientists are using to understand how HD affects brain development. In a CIRM-funded study published today in the journal Nature Neuroscience, scientists from the HD iPSC Consortium used HD iPSCs to study how the HD mutation causes problems with neurodevelopment.

They analyzed neural cells made from HD patient iPSCs and looked at what genes displayed abnormal activity compared to healthy neural cells. Using a technique called RNA-seq analysis, they found that many of these “altered” genes in HD cells played important roles in the development and maturation of neurons, the nerve cells in the brain. They also observed differences in the structure of HD neurons compared to healthy neurons when grown in a lab. These findings suggest that HD patients likely have problems with neurodevelopment and adult neurogenesis, the process where the adult stem cells in your brain generate new neurons and other brain cells.

After pinpointing the gene networks that were altered in HD neurons, they identified a small molecule drug called isoxazole-9 (Isx-9) that specifically targets these networks and rescues some of the HD-related symptoms they observed in these neurons. They also tested Isx-9 in a mouse model of HD and found that the drug improved their cognition and other symptoms related to impaired neurogenesis.

The authors conclude from their findings that the HD mutation disrupts gene networks that affect neurodevelopment and neurogenesis. These networks can be targeted by Isx-9, which rescues HD symptoms and improves the mental capacity of HD mice, suggesting that future treatments for HD should focus on targeting these early stage events.

I reached out to the leading authors of this study to gain more insights into their work. Below is a short interview with Dr. Leslie Thompson from UC Irvine, Dr. Clive Svendsen from Cedars-Sinai, and Dr. Steven Finkbeiner from the Gladstone Institutes. The responses were mutually contributed.

Leslie Thompson

Steven Finkbeiner

Clive Svendsen

 

 

 

 

 

 Q: What is the mission of the HD iPSC Consortium?

To create a resource for the HD community of HD derived stem cell lines as well as tackling problems that would be difficult to do by any lab on its own.  Through the diverse expertise represented by the consortium members, we have been able to carry out deep and broad analyses of HD-associated phenotypes [observable characteristics derived from your genome].  The authorship of the paper  – the HD iPSC consortium (and of the previous consortium paper in 2012) – reflects this goal of enabling a consortium and giving recognition to the individuals who are part of it.

Q: What is the significance of the findings in your study and what novel insights does it bring to the HD field?

 Our data revealed a surprising neurodevelopmental effect of highly expanded repeats on the HD neural cells.  A third of the changes reflected changes in networks that regulate development and maturation of neurons and when compared to neurodevelopment pathways in mice, showed that maturation appeared to be impacted.  We think that the significance is that there may be very early changes in HD brain that may contribute to later vulnerability of the brain due to the HD mutation.  This is compounded by the inability to mount normal adult neurogenesis or formation of new neurons which could compensate for the effects of mutant HTT.  The genetic mutation is present from birth and with differentiated iPSCs, we are picking up signals earlier than we expected that may reflect alterations that create increased susceptibility or limited homeostatic reserves, so with the passage of time, symptoms do result.

What we find encouraging is that using a small molecule that targets the pathways that came out of the analysis, we protected against the impact of the HD mutation, even after differentiation of the cells or in an adult mouse that had had the mutation present throughout its development.

Q: There’s a lot of evidence suggesting defects in neurodevelopment and neurogenesis cause HD. How does your study add to this idea?

Agree completely that there are a number of cell, mouse and human studies that suggest that there are problems with neurodevelopment and neurogenesis in HD.  Our study adds to this by defining some of the specific networks that may be regulating these effects so that drugs can be developed around them.  Isx9, which was used to target these pathways specifically, shows that even with these early changes, one can potentially alleviate the effects. In many of the assays, the cells were already through the early neurodevelopmental stages and therefore would have the deficits present.  But they could still be rescued.

Q: Has Isx-9 been used previously in cell or animal models of HD or other neurodegenerative diseases? Could it help HD patients who already are symptomatic?

The compound has not been used that we know of in animal models to treat neurodegeneration, although was shown to affect neurogenesis and memory in mice. Isx9 was used in a study by Stuart Lipton in Parkinson’s iPSC-derived neurons in one study and it had a protective effect on apoptosis [cell death] in a study by Ryan SD et al., 2013, Cell.

We think this type of compound could help patients who are symptomatic.  Isx-9 itself is a fairly pleiotropic drug [having multiple effects] and more research would be needed [to test its safety and efficacy].

Q: Have you treated HD mice with Isx-9 during early development to see whether the molecule improves HD symptoms?

Not yet, but we would like to.

Q: What are your next steps following this study and do you have plans to translate this research into humans?

We are following up on the research in more mature HD neurons and to determine at what stages one can rescue the HD phenotypes in mice.  Also, we would need to do pharmacodynamics and other types of assays in preclinical models to assess efficacy and then could envision going into human trials with a better characterized drug.  Our goal is to ultimately translate this to human treatments in general and specifically by targeting these altered pathways.

Stem Cell Stories that Caught our Eye: stem cell insights into anorexia, Zika infection and bubble baby disease

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.

Stem cell model identifies new culprit for anorexia.

Eating disorders like anorexia nervosa are often thought to be caused by psychological disturbances or societal pressure. However, research into the genes of anorexia patients suggests that what’s written in your DNA can be associated with an increased vulnerability to having this disorder. But identifying individual genes at fault for a disease this complex has remained mostly out of scientists’ reach, until now.

A CIRM-funded team from the UC San Diego (UCSD) School of Medicine reported this week that they’ve developed a stem cell-based model of anorexia and used it to identify a gene called TACR1, which they believe is associated with an increased likelihood of getting anorexia.

They took skin samples from female patients with anorexia and reprogrammed them into induced pluripotent stem cells (iPSCs). These stem cells contained the genetic information potentially responsible for causing their anorexia. The team matured these iPSCs into brain cells, called neurons, in a dish, and then studied what genes got activated. When they looked at the genes activated by anorexia neurons, they found that TACR1, a gene associated with psychiatric disorders, was switched on higher in anorexia neurons than in healthy neurons. These findings suggest that the TACR1 gene could be an identifier for this disease and a potential target for developing new treatments.

In a UCSD press release, Professor and author on the study, Alysson Muotri, said that they will follow up on their findings by studying stem cell lines derived from a larger group of patients.

Alysson Muotri UC San Diego

“But more to the point, this work helps make that possible. It’s a novel technological advance in the field of eating disorders, which impacts millions of people. These findings transform our ability to study how genetic variations alter brain molecular pathways and cellular networks to change risk of anorexia nervosa — and perhaps our ability to create new therapies.”

Anorexia is a disease that affects 1% of the global population and although therapy can be an effective treatment for some, many do not make a full recovery. Stem cell-based models could prove to be a new method for unlocking new clues into what causes anorexia and what can cure it.

Nature versus Zika, who will win?

Zika virus is no longer dominating the news headlines these days compared to 2015 when large outbreaks of the virus in the Southern hemisphere came to a head. However, the threat of Zika-induced birth defects, like microcephaly to pregnant women and their unborn children is no less real or serious two years later. There are still no effective vaccines or antiviral drugs that prevent Zika infection but scientists are working fast to meet this unmet need.

Speaking of which, scientists at UCLA think they might have a new weapon in the war against Zika. Back in 2013, they reported that a natural compound in the body called 25HC was effective at attacking viruses and prevented human cells from being infected by viruses like HIV, Ebola and Hepatitis C.

When the Zika outbreak hit, they thought that this compound could potentially be effective at preventing Zika infection as well. In their new study published in the journal Immunity, they tested a synthetic version of 25HC in animal and primate models, they found that it protected against infection. They also tested the compound on human brain organoids, or mini brains in a dish made from pluripotent stem cells. Brain organoids are typically susceptible to Zika infection, which causes substantial cell damage, but this was prevented by treatment with 25HC.

Left to right: (1) Zika virus (green) infects and destroys the formation of neurons (pink) in human stem cell-derived brain organoids.  (2) 25HC blocks Zika infection and preserves neuron formation in the organoids. (3) Reduced brain size and structure in a Zika-infected mouse brain. (4) 25HC preserves mouse brain size and structure. Image courtesy of UCLA Stem Cell.

A UCLA news release summarized the impact that this research could have on the prevention of Zika infection,

“The new research highlights the potential use of 25HC to combat Zika virus infection and prevent its devastating outcomes, such as microcephaly. The research team will further study whether 25HC can be modified to be even more effective against Zika and other mosquito-borne viruses.”

Harnessing a naturally made weapon already found in the human body to fight Zika could be an alternative strategy to preventing Zika infection.

Gene therapy in stem cells gives hope to bubble-babies.

Last week, an inspiring and touching story was reported by Erin Allday in the San Francisco Chronicle. She featured Ja’Ceon Golden, a young baby not even 6 months old, who was born into a life of isolation because he lacked a properly functioning immune system. Ja’Ceon had a rare disease called severe combined immunodeficiency (SCID), also known as bubble-baby disease.

 

Ja’Ceon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski. Photo: Santiago Mejia, The Chronicle.

Babies with SCID lack the body’s immune defenses against infectious diseases and are forced to live in a sterile environment. Without early treatment, SCID babies often die within one year due to recurring infections. Bone marrow transplantation is the most common treatment for SCID, but it’s only effective if the patient has a donor that is a perfect genetic match, which is only possible for about one out of five babies with this disease.

Advances in gene therapy are giving SCID babies like Ja’Ceon hope for safer, more effective cures. The SF Chronicle piece highlights two CIRM-funded clinical trials for SCID run by UCLA in collaboration with UCSF and St. Jude Children’s Research Hospital. In these trials, scientists isolate the bone marrow stem cells from SCID babies, correct the genetic mutation causing SCID in their stem cells, and then transplant them back into the patient to give them a healthy new immune system.

The initial results from these clinical trials are promising and support other findings that gene therapy could be an effective treatment for certain genetic diseases. CIRM’s Senior Science Officer, Sohel Talib, was quoted in the Chronicle piece saying,

“Gene therapy has been shown to work, the efficacy has been shown. And it’s safe. The confidence has come. Now we have to follow it up.”

Ja’Ceon was the first baby treated at the UCSF Benioff Children’s Hospital and so far, he is responding well to the treatment. His great aunt Dannie Hawkins said that it was initially hard for her to enroll Ja’Ceon in this trial because she was a partial genetic match and had the option of donating her own bone-marrow to help save his life. In the end, she decided that his involvement in the trial would “open the door for other kids” to receive this treatment if it worked.

Ja’Ceon Golden plays with patient care assistant Grace Deng in a sterile play area at UCSF Benioff Children’s Hospital.Photo: Santiago Mejia, The Chronicle

It’s brave patients and family members like Ja’Ceon and Dannie that make it possible for research to advance from clinical trials into effective treatments for future patients. We at CIRM are eternally grateful for their strength and the sacrifices they make to participate in these trials.

Building the World’s Largest iPSC Repository: An Interview with CIRM’s Stephen Lin

This blog originally appeared on RegMedNet and was provided by Freya Leask, Editor & Community Manager of RegMedNet. In this interview, Stephen Lin, Senior Science Officer at the California Institute Regenerative Medicine (CIRM), discusses the scope, challenges and potential of CIRM’s iPSC Initiative. 

 

Stephen Lin

Stephen Lin received his PhD from Washington University (MO, USA) and completed his postdoctoral work at Harvard University (MA, USA). Lin is a senior science officer at CIRM which he joined in 2015 to oversee the development of a $32 million repository of iPSCs generated from up to 3000 healthy and diseased individuals and covering both complex and rare diseases. He also oversees a $40 million initiative to apply genomics and bioinformatics approaches to stem cell research and development of therapies. Lin is the program lead on the CIRM Translating Center which focuses on supporting the process development, safety/toxicity studies and manufacturing of stem cell therapy candidates to prepare them for clinical trials. He was previously a scientist at StemCells, Inc (CA, USA) and a staff scientist team lead at Thermo Fisher Scientific (MA, USA).

Q: Please introduce yourself and your institution.

I completed my PhD at Washington University in biochemistry, studying the mechanisms of aging, before doing my postdoc at Harvard, investigating programmed cell death. After that, I went into industry and have been working with stem cells ever since.

I was at the biotech company StemCells, Inc for 6 years where I worked on cell therapeutics. I then joined what was Life Technologies which is now Thermo Fisher Scientific.  I joined CIRM in 2015 as they were launching two new initiatives, the iPSC repository and the genomics initiative, which were a natural combination of my experience in both the stem cells industry and in genetic analysis.  I’ve been here for a year and a half, overseeing both initiatives as well as the CIRM Translating Center.

Q: What prompted the development of the iPSC repository?

Making iPSCs is challenging! It isn’t trivial for many research labs to produce these materials, especially for a wide variety of diseases; hence, the iPSC repository was set up in 2013. In its promotion of stem cells, CIRM had the financial resources to develop a bank for researchers and build up a critical mass of lines to save researchers the trouble of recruiting the patients, getting the consents, making and quality controlling the cells. CIRM wanted to cut that out and bring the resources straight to the research community.

Q: What are the challenges of storage so many iPSCs?

Many of the challenges of storing iPSCs and ensuring their quality are overcome with adequate quality controls at the production step. The main challenge is that we’re collecting samples from up to 3000 donors – the logistics of processing that many tissue samples from 11 funded and nonfunded collectors are difficult. The lines are being produced in the same uniform manner by one agency, Cellular Dynamics International (WI, USA), to ensure quality in terms of pluripotency, karyotyping and sterility testing.

Once the lines are made, they are stored at the Coriell Institute (NJ, USA). During storage, there is a challenge in simply keeping track of and distributing that many samples; we will have approximately 40 vials for each of the 3000 main lines. Both Cellular Dynamics and Coriell have sophisticated tracking systems and Coriell have set up a public catalog website where anyone can go to read about and order the lines. Most collections don’t have this functionality, as the IT infrastructure required for searching and displaying the lines along with clinical information, the ordering process, material transfer agreements and, for commercial uses, the licensing agreements was very complex.

Q: Can anyone use the repository?

Yes, they can! There is a fee to utilize the lines but we encourage researchers anywhere in the world to order them. The lines are mostly for research and academic purposes but the collection was built to be commercialized, all the way from collecting the samples. When the samples were collected, the patient consent included, among other things, banking, distribution, genetic characterization and commercialization.

The lines also have pre-negotiated licensing agreements with iPS Academia Japan (Kyoto, Japan) and the Wisconsin Alumni Research Foundation (WI, USA). Commercial entities that want to use the cells for drug screening can obtain a license which allows them to use these lines for drug discovery and drug screening purposes without fear of back payment royalties down the road. People often forget during drug screening that the intellectual property to make the iPSCs is still under patent, so if you do discover a drug using iPSCs without taking care of these licensing agreements, your discovery could be liable to ownership by that original intellectual property holder.

Q: Will wider access to high quality iPSCs accelerate discovery?

That’s our hope. When people make iPSCs, the quality can be highly variable depending on the lab’s background and experience, which was another impetus to create the repository. Cellular Dynamics have set up a very robust system to create these lines in a rigorous quality control pipeline to guarantee that these lines are pluripotent and genetically stable.

Q: What diseases could these lines be used to study and treat?

We collected samples from patients with many different diseases – from neurodevelopmental disorders including epilepsy and neurodegenerative diseases such as Alzheimer’s, to eye disease and diabetes – as well as the corresponding controls. We also have lines from rare diseases, where the communities have no other tools to study them, for example, ADCY5 related dyskinesia. You can read our recent blogs about our efforts to generate new iPSC lines for ADCY5 and other rare diseases here and here.

Q: What are your plans for the iPSC initiative this year?

We’re currently the largest publicly available repository in the world and we aren’t complete yet. We have just under half of the lines in with the other half still being produced and quality controlled. Something else we want to do is add further information to make the lines more valuable and ensure the drug models are constantly improving. The reason people will want to use iPSCs for human disease modeling is whether they have valuable information associated with them.  For example, we are trying to add genetic and sequencing information to the catalog for lines that have it. This will also allow researchers to prescreen the lines they are interested in to match the diseases and drugs they are studying.

Q: Does the future for iPSCs lie in being utilized as tools to find therapeutics as opposed to therapeutics themselves?

I think the future is two pronged. There is certainly a future for disease modeling and drug screening. There is currently an initiative within the FDA, the CiPA initiative, is designed to replace current paradigms for drug safety testing with computational model and stem cell models. In particular, they hope to be able to screen drugs for cardiotoxicity in stem cells before they go to patients.  Mouse and rodent models have different receptors and ion channels so these cardiotoxic effects aren’t usually seen until clinical trials.

The other avenue is in therapeutics. However, this will come later in the game because the lines being used for research often can’t be used for therapeutics. Patient consent for therapeutic use has to be obtained at sample collection, the tissue should be handled in compliance with good lab practice and the lines must be produced following good manufacturing process (GMP) guidelines. They must then be characterized to ensure they have met all safety protocols for iPSC therapeutics.

There is already a second trial being initiated in Japan of an iPSC therapeutic to treat macular degeneration, utilizing allogenic lines that are human leukocyte antigen-compatible and extensively safety profiled. Companies such as Lonza (Basel, Switzerland) and Cellular Dynamics are starting to produce their own GMP lines, and CIRM is funding some translation programs where clinical grade iPSCs are being produced for therapeutics.


Further Reading

Stem cell stories that caught our eye: drug safety for heart cells, worms hijack plant stem cells & battling esophageal cancer

Devising a drug safety measuring stick in stem cell-derived heart muscle cells
One of the mantras in the drug development business is “fail early”. That’s because most of the costs of getting a therapy to market occur at the later stages when an experimental treatment is tested in clinical trials in people. So, it’s best for a company’s bottom line and, more importantly, for patient safety to figure out sooner rather than later if a therapy has dangerous toxic side effects.

Researchers at Stanford reported this week in Science Translational Medicine on a method they devised that could help weed out cancer drugs with toxic effects on the heart before the treatment is tested in people.

In the lab, the team grew beating heart muscle cells, or cardiomyocytes, from induced pluripotent stem cells derived from both healthy volunteers and kidney cancer patients. A set of cancer drugs called tyrosine kinase inhibitors which are known to have a range of serious side effects on the heart, were added to the cells. The effect of the drugs on the heart cell function were measured with several different tests which the scientists combined into a single “safety index”.

roundup_wu

A single human induced pluripotent stem cell-derived cardiomyocyte. Cells such as these were used to assess tyrosine kinase inhibitors for cardiotoxicity in a high-throughput fashion. Credit: Dr. Arun Sharma at Dr. Joseph Wu’s laboratory at Stanford University

They found that the drugs previously shown to have toxic effects on patients’ hearts had the worst safety index values in the current study. And because these cells were in a lab dish and not in a person’s heart, the team was able to carefully examine cell activity and discovered that the toxic effects of three drugs could be alleviated by also adding insulin to the cells.

As lead author Joseph Wu, director of the Stanford Cardiovascular Institute, mentions in a press release, the development of this drug safety index could provide a powerful means to streamline the drug development process and make the drugs safer:

“This type of study represents a critical step forward from the usual process running from initial drug discovery and clinical trials in human patients. It will help pharmaceutical companies better focus their efforts on developing safer drugs, and it will provide patients more effective drugs with fewer side effects”

Worm feeds off of plants by taking control of their stem cells
In what sounds like a bizarre mashup of a vampire movie with a gardening show, a study reported this week pinpoints how worms infiltrate plants by commandeering the plants’ own stem cells. Cyst nematodes are microscopic roundworms that invade and kill soybean plants by sucking out their nutrients. This problem isn’t a trivial matter since nematodes wreak billions of dollars of damage to the world’s soybean crops each year. So, it’s not surprising that researchers want to understand how exactly these critters attack the plants.

nematode-feeding-site

A nematode, the oblong object on the left, activates the vascular stem cell pathway in the developing nematode feeding site on a plant root. Credit: Xiaoli Guo, University of Missouri

Previous studies by Melissa Goellner Mitchum, a professor at the University of Missouri, had shown that the nematodes release protein fragments, called peptides, near a plant’s roots that help divert the flow of plant nutrients to the worm.

“These parasites damage root systems by creating a unique feeding cell within the roots of their hosts and leeching nutrients out of the soybean plant. This can lead to stunting, wilting and yield loss for the plant,” Mitchum explained in a press release.

In the current PLOS Pathogens study, Mitchum’s team identified another peptide produced by the nematode that is identical to a plant peptide that instructs stem cells to form the plant equivalent of blood vessels. This devious mimicking of the plant peptides is what allows the nematode to trick the plant stem cells into building vessels that reroute the plants’ nutrients directly to the worm.

Mitchum described the big picture implications of this fascinating discovery:

“Understanding how plant-parasitic nematodes modulate host plants to their own benefit is a crucial step in helping to create pest-resistant plants. If we can block those peptides and the pathways nematodes use to overtake the soybean plant, then we can enhance resistance for this very valuable global food source.”

Finding vulnerabilities in treatment-resistant esophageal cancer stem cells

diagram_showing_internal_radiotherapy_for_cancer_of_the_oesophagus_cruk_162-svg

Illustration of radiation therapy for esophageal cancer.
Credit: Cancer Research UK

The incidence of esophageal cancer has increased more than any other disease over the past 30 years. And while some patients respond well to chemotherapy and radiation treatment, most do not because the cancer becomes resistant to these treatments.

Focusing on cancer stem cells, researchers at Trinity College Dublin have identified an approach that may overcome treatment resistance.

Within tumors are thought to lie cancer stem cells that, just like stem cells, have the ability to multiply indefinitely. Even though they make up a small portion of a tumor, in some patients the cancer stem cells evade the initial rounds of treatment and are responsible for the return of the cancer which is often more aggressive. Currently, there’s no effective way to figure out how well a patient with esophageal cancer will response to treatment.

In the current study published in Oncotarget, the researchers found that a genetic molecule called miR-17 was much less abundant in the esophageal cancer stem cells. In fact, the cancer stem cells with the lowest levels of miR-17, were the most resistant to radiation therapy. The researchers went on to show that adding back miR-17 to the highly resistant cells made them sensitive again to the radiation. Niamh Lynam-Lennon, the study’s first author, explained in a press release that these results could have direct clinical applications:

“Going forward, we could use synthetic miR-17 as an addition to radiotherapy to enhance its effectiveness in patients. This is a real possibility as a number of other synthetic miR-molecules are currently in clinical trials for treating other diseases.”

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

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

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

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

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

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

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

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

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

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

“Apples to Apples” analysis: induced pluripotent stem cell (iPSC) method doesn’t increase mutations

It’s full steam ahead for the development of induced pluripotent stem cell (iPSC)-derived clinical trials. That’s according to a group at the National Human Genome Research Institute in Bethesda, Maryland who report this week in PNAS that the process of reprogramming a skin cell into the embryonic stem cell-like state of an iPSC does not itself cause an increased number of genetic mutations.

logo_nhgriEver since the technique was first devised ten years ago, there has been a lot of excitement about applying IPSCs to cell therapies for patients with unmet medical needs. Unlike human embryonic stem cells (hESCs) which are generated through the destruction of a fertilized embryo, iPSCs avoid ethical concerns because they’re obtained using adult cells like blood or skin. And the fact they’re patient specific carries the additional advantage of delivering iPSC-derived therapies back to the same patient with less concerns of rejection by the immune system.

Still, the use of iPSC-derived therapies has certainly not been worry-free and their translation into human clinical trials has been slow. One big concern is that the process of reprogramming inherently causes cell stress leading to an increased rate of genetic mutations in the cells. An abnormal number of mutations is bad news for cell therapies because they could carry an increased risk of becoming cancerous after being injected into a patient – an event that would end up causing more harm than good. Previous DNA sequencing studies comparing iPSCs with their cell source (skin, blood, etc.) identified many new sequence mutations in the iPSCs. But other studies suggested that many of those mutations already existed in the source cells and so they were essentially inherited during the iPSC process.

The team in this study sought out a definitive answer by tackling this mutation question using an “apples to apples” approach. To explain their approach, let’s first understand a technical detail about the iPSC method. When the iPSC reprogramming factors are added to the adult skin cells, the process is not efficient and only a few become iPSCs. Single iPSCs are then isolated and allowed to divide and make clones of themselves. This population of cells is called a cell “line” and takes several rounds of cell division to multiply into enough numbers to analyze their DNA sequence.

dnasequencing

Credit: Darryl Leja and Ernesto Del Aguila III, NHGRI

So the researchers decided to also go through the process of making cell lines from the original skin cells but in this set they did not add the iPSC reprogramming factors. Now, they could compare the fate of DNA sequences in skin cell lines with and without the iPSC reprogramming method. The sequencing results showed that mutations occurred at the same rate in both the skin cell lines and the iPSC cell lines. This direct comparison suggests that iPSCs aren’t any less stable than non-reprogrammed cells. This finding bodes well for moving ahead with iPS-derived clinical trials. That’s certainly the perspective Erika Mijin Kwon, a co-author on the publication:

“Based on this data, we plan to start using iPSCs to gain a deeper understanding of how diseases start and progress,” said Kwon, in a press release. “We eventually hope to develop new therapies to treat patients with leukemia using their own iPSCs. We encourage other researchers to embrace the use of iPSCs.”

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

multiple-sclerosis

Motor neurons

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

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

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

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

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

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

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Scripps Research Institute

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

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

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

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

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

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

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

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

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

 

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

Stories that caught our eye: $20.5 million in new CIRM discovery awards, sickle cell disease cell bank, iPSC insights

CIRM Board launches a new voyage of Discovery (Kevin McCormack).
Basic or early stage research is the Rodney Dangerfield of science; it rarely gets the respect it deserves. Yesterday, the CIRM governing Board showed that it not only respects this research, but also values its role in laying the foundation for everything that follows.

The CIRM Board approved 11 projects, investing more than $20.5 million in our Discovery Quest, early stage research program. Those include programs using gene editing techniques to develop a cure for a rare but fatal childhood disease, finding a new approach to slowing down the progress of Parkinson’s disease, and developing a treatment for the Zika virus.

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Electron micrograph of Zika virus (red circles). Image: CDC/Cynthia Goldsmith

The goal of the Discovery Quest program is to identify and explore promising new stem cell therapies or technologies to improve patient care.

In a news release Randy Mills, CIRM’s President & CEO, said we hope this program will create a pipeline of projects that will ultimately lead to clinical trials:

“At CIRM we never underestimate the importance of early stage scientific research; it is the birth place of groundbreaking discoveries. We hope these Quest awards will not only help these incredibly creative researchers deepen our understanding of several different diseases, but also lead to new approaches on how best to use stem cells to develop treatments.”

Creating the world’s largest stem cell bank for sickle cell disease (Karen Ring).
People typically visit the bank to deposit or take out cash, but with advancements in scientific research, people could soon be visiting banks to receive life-saving stem cell treatments. One of these banks is already in the works. Scientists at the Center for Regenerative Medicine (CReM) at Boston Medical Center are attempting to generate the world’s largest stem cell bank focused specifically on sickle cell disease (SCD), a rare genetic blood disorder that causes red blood cells to take on an abnormal shape and can cause intense pain and severe organ damage in patients.

To set up their bank, the team is collecting blood samples from SCD patients with diverse ethnic backgrounds and making induced pluripotent stem cells (iPSCs) from these samples. These patient stem cell lines will be used to unravel new clues into why this disease occurs and to develop new potential treatments for SCD. More details about this new SCD iPSC bank can be found in the latest edition of the journal Stem Cell Reports.

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Gustavo Mostoslavsky, M.D., PH.D., Martin Steinberg, M.D., George Murphy PH.D.
Photo: Boston Medical Center

In a news release, CReM co-founder and Professor, Gustavo Mostoslavsky, touched on the future importance of their new stem cell bank:

“In addition to the library, we’ve designed and are using gene editing tools to correct the sickle hemoglobin mutation using the stem cell lines. When coupled with corrected sickle cell disease specific iPSCs, these tools could one day provide a functional cure for the disorder.”

For researchers interested in using these new stem cell lines, CReM is making them available to researchers around the world as part of the NIH’s NextGen Consortium study.

DNA deep dive reveals ways to increase iPSC efficiency (Todd Dubnicoff)
Though the induced pluripotent stem (iPS) cell technique was first described ten years ago, many researchers continue to poke, prod and tinker with the method which reprograms an adult cell, often from skin, into an embryonic stem cell-like state which can specialize into any cell type in the body. Though this breakthrough in stem cell research is helping scientists better understand human disease and develop patient-specific therapies, the technique is hampered by its low efficiency and consistency.

This week, a CIRM-funded study from UCLA reports new insights into the molecular changes that occur during reprogramming that may help pave the way toward better iPS cell methods. The study, published in Cell, examined the changes in DNA during the reprogramming process.

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Senior authors Kathrin Plath and Jason Ernst and first authors Petko Fiziev and Constantinos Chronis.
Photo: UCLA

In a skin cell, the genes necessary for embryonic stem cell-like, or pluripotent, characteristics are all turned off. One way this shut down in gene activity occurs is through tight coiling of the DNA where the pluripotent genes are located. This physically blocks proteins called transcriptions factors from binding the DNA and activating those pluripotent genes within skin cells. On the other hand, regions of DNA carrying skin-related genes are loosely coiled, so that transcription factors can access the DNA and turn on those genes.

The iPS cell technique works by artificially adding four pluripotent transcriptions factors into skin cells which leads to changes in DNA coiling such that skin-specific genes are turned off and pluripotent genes are turned on. The UCLA team carefully mapped the areas where the transcription factors are binding to DNA during the reprogramming process. They found that the shut down of the skin genes and activation of the pluripotent genes occurs at the same time. The team also found that three of the four iPS cell factors must physically interact with each other to locate and activate the areas of DNA that are responsible for reprogramming.

Using the findings from those experiments, the team was able to identify a fifth transcription factor that helps shut down the skin-specific gene more effectively and, in turn, saw a hundred-fold increase in reprogramming efficiency. These results promise to help the researchers fine-tune the iPS cell technique and make its clinical use more practical.

Has the promise of stem cells been overstated?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hank Greely, Stanford University

Hank Greely, Stanford University

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

 


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