One-Time, Lasting Treatment for Sickle Cell Disease May be on Horizon, According to New CIRM-Funded Study

For the nearly 1,000 babies born each year in the United States with sickle cell disease, a painful and arduous road awaits them. The only cure is to find a bone marrow donor—an exceedingly rare proposition. Instead, the standard treatment for this inherited blood disorder is regular blood transfusions, with repeated hospitalizations to deal with complications of the disease. And even then, life expectancy is less than 40 years old.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

But now, scientists at UCLA are offering up a potentially superior alternative: a new method of gene therapy that can correct the genetic mutation that causes sickle cell disease—and thus help the body on its way to generate normal, healthy blood cells for the rest of the patient’s life. The study, funded in part by CIRM and reported in the journal Blood, offers a great alternative to developing a functional cure for sickle cell disease. The UCLA team is about to begin a clinical trial with another gene therapy method, so they—and their patients—will now have two shots on goal in their effort to cure the disease.

Though sickle cell disease causes dangerous changes to a patient’s entire blood supply, it is caused by one single genetic mutation in the beta-globin gene—altering the shape of the red blood cells from round and soft to pointed and hard, thus resembling a ‘sickle’ shape for which the disease is named. But the UCLA team, led by Donald Kohn, has now developed two methods that can correct the harmful mutation. As he explained in a UCLA news release about the newest technique:

“[These results] suggest the future direction for treating genetic diseases will be by correcting the specific mutation in a patient’s genetic code. Since sickle cell disease was the first human genetic disease where we understood the fundamental gene defect, and since everyone with sickle cell has the exact same mutation in the beta-globin gene, it is a great target for this gene correction method.”

The latest gene correction technique used by the team uses special enzymes, called zinc-finger nucleases, to literally cut out and remove the harmful mutation, replacing it with a corrected version. Here, Kohn and his team collected bone marrow stem cells from individuals with sickle cell disease. These bone marrow stem cells would normally give rise to sickle-shaped red blood cells. But in this study, the team zapped them with the zinc-finger nucleases in order to correct the mutation.

Then, the researchers implanted these corrected cells into laboratory mice. Much to their amazement, the implanted cells began to replicate—into normal, healthy red blood cells.

Kohn and his team worked with Sangamo BioSciences, Inc. to design the zinc-finger nucleases that specifically targeted and cut the sickle-cell mutation. The next steps will involve improving the efficiency and safest of this method in pre-clinical animal models, before moving into clinical trials.

“This is a promising first step in showing that gene correction has the potential to help patients with sickle cell disease,” said UCLA graduate student Megan Hoban, the study’s first author. “The study data provide the foundational evidence that the method is viable.”

This isn’t the first disease for which Kohn’s team has made significant strides in gene therapy to cure blood disorders. Just last year, the team announced a promising clinical trial to cure Severe Combined Immunodeficiency Syndrome, also known as SCID or “Bubble Baby Disease,” by correcting the genetic mutation that causes it.

While this current study still requires more research before moving into clinical trials, Kohn and his team announced last month that their other gene therapy method, also funded by CIRM, has been approved to start clinical trials. Kohn argues that it’s vital to explore all promising treatment options for this devastating condition:

“Finding varied ways to conduct stem cell gene therapies is important because not every treatment will work for every patient. Both methods could end up being viable approaches to providing one-time, lasting treatments for sickle cell disease and could also be applied to the treatment of a large number of other genetic diseases.”

Find Out More:
Read first-hand about Sickle Cell Disease in our Stories of Hope series.
Watch Donald Kohn speak to CIRM’s governing Board about his research.

Stay on Target: Scientists Create Chemical ‘Homing Devices’ that Guide Stem Cells to Final Destination

When injecting stem cells into a patient, how do the cells know where to go? How do they know to travel to a specific damage site, without getting distracted along the way?

Scientists are now discovering that, in some cases they do but in many cases, they don’t. So engineers have found a way to give stem cells a little help.

As reported in today’s Cell Reports, engineers at Brigham and Women’s Hospital (BWH) in Boston, along with scientists at the pharmaceutical company Sanofi, have identified a suite of chemical compounds that can help the stem cells find their way.

Researchers identified a small molecule that can be used to program stem cells (blue and green) to home in on sites of damage. [Credit: Oren Levy, Brigham and Women's Hospital]

Researchers identified a small molecule that can be used to program stem cells (blue and green) to home in on sites of damage. [Credit: Oren Levy, Brigham and Women’s Hospital]

“There are all kinds of techniques and tools that can be used to manipulate cells outside the body and get them into almost anything we want, but once we transplant cells we lose complete control over them,” said Jeff Karp, the paper’s co-senior author, in a news release, highlighting just how difficult it is to make sure the stem cells reach their destination.

So, Karp and his team—in collaboration with Sanofi—began to screen thousands of chemical compounds, known as small molecules, that they could physically attach to the stem cells prior to injection and that could guide the cells to the appropriate site of damage. Not unlike a molecular ‘GPS.’

Starting with more than 9,000 compounds, the Sanofi team narrowed down the candidates to just six. They then used a microfluidic device—a microscope slide with tiny glass channels designed to mimic human blood vessels. Stem cells pretreated with the compound Ro-31-8425 (one of the most promising of the six) stuck to the sides. An indication, says the team, Ro-31-8425 might help stem cells home in on their target.

But how would these pre-treated cells fare in animal models? To find out, Karp enlisted the help of Charles Lin, an expert in optical imaging at Massachusetts General Hospital. First, the team injected the pre-treated cells into mouse models each containing an inflamed ear. Then, using Lin’s optical imaging techniques, they tracked the cells’ journey. Much to their excitement, the cells went immediately to the site of inflammation—and then they began to repair the damage.

According to Oren Levy, the study’s co-first author, these results are especially encouraging because they point to how doctors may someday soon deliver much-needed stem cell therapies to patients:

“There’s a great need to develop strategies that improve the clinical impact of cell-based therapies. If you can create an engineering strategy that is safe, cost effective and simple to apply, that’s exactly what we need to achieve the promise of cell-based therapy.”

Stem cell stories that caught our eye; progress toward artificial brain, teeth may help the blind and obesity

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.

More progress toward artificial brain. A team at the RIKEN Institute in Japan has used stem cells in a 3-D culture to create brain tissue more complex than prior efforts and from an area of the brain not produced before, the cerebellum—that lobe at the lower back of the brain that controls motor function and attention. As far back as 2008, a RIKEN team had created simple tissue that mimicked the cortex, the large surface area that controls memory and language.

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The Inquisitr web portal wrote a feature on a wide variety of efforts to create an artificial brain teeing off of this week’s publication of the cerebellum work in Cell Reports. The piece is fairly comprehensive covering computerized efforts to give robots intelligence and Europe’s Human Brain Project that is trying to map all the activity of the brain as a starting point for recapitulating it in the lab.

The experts interviewed included Robert Caplan of Tufts University in Massachusetts who is using 3-D scaffolding to build functional brain tissues that can process electrical signals. He is not planning any Frankenstein moments; he hopes to create models to improve understanding of brain diseases.

“Ideally we would like to have a laboratory brain system that recapitulates the most devastating diseases. We want to be able to take our existing toolkit of drugs and understand how they work instead of using trial and error.”

Teeth eyed as source of help for the blind. Today the European Union announced the first approval of a stem cell therapy for blindness. And already yesterday a team at the University of Pittsburg announced they had developed a new method to use stem cells to restore vision that could expand the number of patients who could benefit from stem cell therapy.

Many people have lost part or all their vision due to damage to the cornea on the surface of their eye. Even when they can gain vision back through a corneal transplant, their immune system often rejects the new tissue. So the ideal would be making new corneal tissue from the patient’s own cells. The Italian company that garnered the EU approval does this in patients by harvesting some of their own cornea-specific stem cells, called limbal stem cells. But this is only an option if only one eye is impacted by the damage.

The Pittsburgh team thinks it may have found an unlikely alternative source of limbal cells: the dental pulp taken from teeth that have be extracted. It is not as far fetched at it sounds on the surface. Teeth and the cornea both develop in the same section of the embryo, the cranial neural crest. So, they have a common lineage.

The researchers first treated the pulp cells with a solution that makes them turn into the type of cells found in the cornea. Then they created a fiber scaffold shaped like a cornea and seeded the cells on it. Many steps remain before people give up a tooth to regain their sight, but this first milestone points the way and was described in a press release from the journal Stem Cells Translational Medicine, which was picked up by the web site ClinicaSpace.

CIRM funds a project that also proposes to use the patient’s own limbal stem cells but using methods more likely to gain approval of the Food and Drug Administration than those used by the Italian company.

Stem cells and the fight against obesity. Of the two types of stem cells found in your bone marrow, one can form bone and cartilage and, all too often, fat. Preventing these stem cells from maturing into fat may be a tool in the fight against obesity according to a team at Queen Mary University of London.

The conversion of stem cells to fat seems to involve the cilia, or hair-like projections found on cells. When the cilia lengthen the stem cells progress toward becoming fat. But if the researchers genetically prevented that lengthening, they stopped the conversion to fat cells. The findings opens several different ways to think about understanding and curbing obesity says Melis Dalbay one of the authors of the study in a university press release picked up by ScienceNewsline.

“This is the first time that it has been shown that subtle changes in primary cilia structure can influence the differentiation of stem cells into fat. Since primary cilia length can be influenced by various factors including pharmaceuticals, inflammation and even mechanical forces, this study provides new insight into the regulation of fat cell formation and obesity.”

Roadmap to our epigenome reveals the genetic switches that make one adult cell type different from others

A decade ago scientists made a huge news splash when they announced the completion of the human genome project declaring it the first road map of our genes. But it did not take long to realize that the early road map was like some of the early days of GPS systems: it lacked knowledge of many on-ramps, off-ramps and one-way streets.

Today, the scientific world announced a massive fix to its genetic GPS. While all of our cells carry the same genes, their function varies wildly based one which genes are turned off, which are turned on, and even which are turned on in a hyper active way. Complex chemical and structural changes in the chromosomes that house our genes—collectively called the epigenome—determine that activity.

This video from Nature explaining the epigenome with music metaphors is linked in the last paragraph.

This video from Nature explains the epigenome with music metaphors.


A massive project, mostly funded by the National Institutes of Health through a consortium of research teams around the country, published a series of papers today in Nature. The Roadmap Epigenomic Consortium did extensive analysis of 111 epigenomes from different types of cells: normal heart tissue and immune cells, for example, as well as cells from patients with diseases such as neurons from patients with Alzheimer’s. The Scientist this morning quoted one member of the Consortium, MIT’s Manolis Kellis:

“The human epigenome is this collection of . . . chemical modifications on the DNA itself and on the packaging that holds DNA together. All our cells have a copy of the same book, but they’re all reading different chapters, bookmarking different pages, and highlighting different paragraphs and words.”

CIRM funding contributed to two of the papers authored by a team at the University of California, San Diego. One of the papers looked at how the genetic structure of stem cells changes as they mature and differentiate into specific types of adult tissue. The other looked at how structural differences determine which of the chromosomes we inherit—the one from mom or the one from dad—has a stronger influence on specific traits. The senior author on the studies, Bing Ren, noted in a university press release that these differences will be important as we think about individualizing therapies:

“Both of these studies provide important considerations for clinicians and researchers who are developing personalized medicines based on a patient’s genomic information”

The consortium’s publications today resulted from a massive data analysis. A press release from the Broad Institute in Cambridge, Massachusetts, describes the effort that required grouping two million predicted areas of change in the chromosomes into 200 sets or modules and then looking for how those modules impacted different cell types.

But if you are still having trouble understanding the concept of the epigenome, I highly recommend taking the five minutes it takes to watch this video produced by Nature. It equates the process to a symphony and what occurs when you change notes and intensity in the score.

Combination Cancer Therapy Gives Cells a Knockout Punch

For some forms of cancer, there really is no way to truly eradicate it. Even the most advanced chemotherapy treatments leave behind some straggler cells that can fuel a relapse.

By hitting breast cancer cells with a targeted therapeutic immediately after chemotherapy, researchers were able to target cancer cells during a transitional stage when they were most vulnerable. [Credit: Aaron Goldman]

By hitting breast cancer cells with a targeted therapeutic immediately after chemotherapy, researchers were able to target cancer cells during a transitional stage when they were most vulnerable.
[Credit: Aaron Goldman]

But now, scientists have devised a unique strategy, something they are calling a ‘one-two punch’ that can more effectively wipe out dangerous tumors, and lower the risk of them ever returning for a round two.

Reporting in the latest issue of the journal Nature Communications, bioengineers at Brigham and Women’s Hospital (BWH) in Boston describe how treating breast cancer cells with a targeted drug immediately after chemotherapy was effective at killing the cancer cells and preventing a recurrence. According to lead scientist Shiladitya Sengupta, these findings were wholly unexpected:

“We were studying the fundamentals of how [drug] resistance develops and looking to understand what drives [cancer] relapse. What we found is a new paradigm for thinking about chemotherapy.”

In recent years, many scientists have suggested cancer stem cells are one of the biggest hurdles to curing cancer. Cancer stem cells are proposed to be a subpopulation of cancer cells that are resistant to chemotherapy. As a result, they can propagate the cancer after treatment, leading to a relapse.

In this work, Sengupta and his colleagues treated breast cancer cells with chemotherapy. And here is where things started getting interesting.

After chemotherapy, the breast cancer cells began to morph into cells that bore a close resemblance to cancer stem cells. For a brief period of time after treatment, these cells were neither fully cancer cells, nor fully stem cells. They were in transition.

The team then realized that because these cells were in transition, they may be more vulnerable to attack. Testing this hypothesis in mouse models of breast cancer, the team first zapped the tumors with chemotherapy. And, once the cells began to morph, they then blasted them with a different type of drug. The tumors never grew back, and the mice survived.

Interestingly, the team did not have similar success when they altered the timing of when they administered the therapy. Treating the mice with both types of drugs simultaneously didn’t have the same effect. Neither did increasing the time between treatments. In order to successfully treat the tumor they had a very slim window of opportunity.

“By treating with chemotherapy, we’re driving cells through a transition state and creating vulnerabilities,” said Aaron Goldman, the study’s first author. “This opens up the door: we can then try out different combinations and regimens to find the most effective way to kill the cells and inhibit tumor growth.”

In order to test these combinations, the researchers developed an ‘explant,’ a mini-tumor derived from a patient’s biopsy that can be grown in an environment that closely mimics its natural surroundings. The ultimate goal, says Goldman, is to map the precise order and timing of this treatment regimen in order to move toward clinical trials:

“Our goal is to build a regimen that will be [effective] for clinical trials. Once we’ve understood specific timing, sequence of drug delivery and dosage better, it will be easier to translate these findings clinically.”

All Things Being (Un)Equal: Scientists Discover Gene that Breaks Traditional Laws of Inheritance

One of the most fundamental laws of biology is about to be turned on its head, according to new research from scientists at the University of North Carolina (UNC) School of Medicine.

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As reported in the journal PLOS Genetics, UNC researchers identified a gene that does not obey traditional laws that determine how genes get passed down from parents to offspring. In experiments on laboratory mice, they found a gene called R2d2 causes female mice to pass on more genetic information than the males did—an observation that appears to contradict principles of genetic inheritance set forth more than a century ago.

As you may (or may not) remember from freshmen biology class, the laws of inheritance were laid down by the 19th century monk Gregor Mendel. Through meticulous observations of his garden’s pea plants, he found that each parent contributes their genetic information equally to their offspring.

But 150 years of scientific discovery later, scientists have discovered that this isn’t always the case.

Instead, in some cases one of the parents will contribute a greater percentage of genetic information than the other, a process called meiotic drive. Scientists had seen evidence of this process occurring in mammals for quite some time, but hadn’t narrowed down the driver of the process to a particular gene. According to UNC researchers, R2d2 is that gene. Senior author Fernando Pardo-Manuel de Villena explains:

“R2d2 is a good example of a poorly understood phenomenon known as female meiotic drive—when an egg is produced and a ‘selfish gene’ is segregated to the egg more than half the time.”

Pardo-Manuel de Villena notes that one example of this process occurs during trisomies—when three chromosomes (two from one parent and one from the other) are passed down to the embryo. The most common trisomy, trisomy 21, is more commonly known as Down Syndrome.

With these findings, Pardo-Manuel de Villena and the team are hoping to gain important insights into the underlying cause of trisomies, as well as the underlying causes for miscarriage—which are often not known.

“Understanding how meiotic drive works may shed light on the … abnormalities underlying these disorders,” said Pardo-Manuel de Villena.

This research was performed in large part by first author John Didion, who first discovered R2d2 when breeding two different types of mice for genetic analysis. Using whole-genome sequencing of thousands of laboratory mice, Didion and his colleagues saw that genes were passed down equally from each mouse’s parents. But a small section, smack dab in the middle of chromosome 2, was different.

Further analysis revealed that this section of chromosome 2 had a disproportionately larger number of genes from the mouse’s mother, compared to its father—showing a clear example of female meiotic drive. And at the heart of it all, Didion discovered, was the R2d2 gene.

The UNC team are already busy diving deeper into the relationship between R2d2 and meiotic drive with a focus on understanding, and one day perhaps correcting, genetic abnormalities in the developing embryo.

MIT Scientists Recreate Malaria in a Dish to Test Promising Drug Candidates

At the beginning, it feels like the flu: aches, pains and vomiting. But then you begin to experience severe cold and shivering, followed by fever and sweating—a cycle, known as tertian fever, that repeats itself every two days. And that’s when you know: you’ve contracted malaria.

Malaria is caused by Plasmodium parasites and spread to people through the bites of infected mosquitoes

Malaria is caused by Plasmodium parasites and spread to people through the bites of infected mosquitoes

But you wouldn’t be alone. According to the World Health Organization, nearly 200 million people, mostly in Africa, contracted the disease in 2013. Of those, nearly half a million—mainly children—died. There is no cure for malaria, and the parasites that cause the disease are quickly developing resistance to treatments. This is a global public health crisis, and experts agree that in order to halt its spread, they must begin thinking outside the box.

Enter Sangeeta Bhatia, renowned biomedical engineer from the Massachusetts Institute of Technology (MIT)—who, along with her team, has devised a quick and easy way to test out life-saving drug candidates that could give doctors and aid workers on the front lines fresh ammunition.

One of the key hurdles facing scientists has been the nature of the disease’s progression itself. Caused by parasites transmitted via infected mosquitos, the disease first takes hold in the liver. It is only after a few weeks that it enters the blood stream, causing symptoms. By then, the disease is so entrenched within the patient that complete eradication is extremely difficult. Even if the patient recovers, he or she will likely suffer relapses weeks, months or even years later.

The trick, therefore, is to catch the disease before it enters the blood stream. To that effect, several promising drugs have been put forth, and scientists are eager to test them out on liver tissue infected with malaria. Except that they can’t: liver tissue donors are few and far between, and lack the genetic diversity needed for large-scale testing.

Liver-stage malarial infection in iPSC-derived liver cells, eight days after infection. [Credit Ng et al.]

Liver-stage malarial infection in iPSC-derived liver cells, eight days after infection. [Credit Ng et al.]

So Bhatia and her team developed a new solution: they’d make the cells themselves. Reporting in today’s issue of Stem Cell Reports, the team describes how they transformed human skin cells into liver cells, by way of induced pluripotent stem cell (iPS cell) technology. Then, by infecting these cells with the malaria parasite, they could test a variety of drug candidates to see which worked best. As Bhatia explained:

“Our platform can be used for testing candidate drugs that act against the parasite in the early liver stages, before it causes disease in the blood and spreads back to the mosquito vector. This is especially important given the increasing occurrence of drug-resistant strains of malaria in the field.”

Bhatia has long been known for finding innovative solutions to longstanding issues in science and medicine. Just last year, she was awarded the prestigious Lemelson-MIT Prize in part for her invention of a paper-based urine test for prostate cancer.

In this study, the researchers bombarded malaria-infected liver cells with two drugs, called atovaguone and primaquine, each developed to treat the disease specifically at the liver stage.

The results, though preliminary, are promising: the cells responded well to both drugs, underscoring the value of this approach to testing drugs—an approach that many call “disease in a dish.”

The potential utility of “disease in a dish” studies cannot be understated, as it gives researchers the ability to screen drugs on cells from individuals of varying genetic backgrounds, and discover which drug, or drugs, works best for each group.

Shengyong Ng, a postdoctoral researcher in Bhatia’s lab, spoke of what this study could mean for disease research:

“The use of iPSC-derived liver cells to model liver-stage malaria in a dish opens the door to study the influence of host genetics on antimalarial drug efficacy, and lays the foundation for their use in antimalarial drug discovery.”

Find out more about how scientists use stem cells to model disease in a dish in our video series, Stem Cells In Your Face.

Money matters: how investing in research advances stem cell science

Our goal at the stem cell agency is simple; to accelerate the development of successful therapies to patients with unmet medical needs. But on the way to doing that something interesting is happening; we’re helping advance the scientific understanding of stem cells and building a robust stem cell research community in California in the process.

You don’t have to take our word for it. A new paper in the journal Cell Stem Cell takes a look at the impact that state funding for stem cell research has had on scientific publications. The question the researchers posed was; have the states that fund stem cell research seen an increase in their share of scientific publications in the field? The answer, at least in California’s case, is absolutely yes.

Let’s back up a little. In the late 1990’s and early 2000’s the field of stem cell research was considered quite controversial, particularly when it came to human embryonic stem cells (hESCs). To help scientists get around some of the restrictions that were placed on the use of federal funds to do hESC research a number of states voted to provide their own funding for this work. This research focuses on four of the biggest supporters of this work: California, Connecticut, Maryland, and New York.

The researchers looked at the following factors:

  1. The percentage of scientific publications in the U.S.
  2. With at least one author from those four states.
  3. That focused on hESCs and induced pluripotent stem cells (iPSCs).
  4. Comparing the numbers from before the state funding kicked in to after.

Finally – stay with me here, we’re almost done – they compared those numbers to the number of publications for two other areas of non-controversial biomedical research, RNAi and cancer. For California the results were clear. The percentage of papers on RNAi and cancer from 1996 – 2013, that had at least one California author, stayed fairly consistent (between 15-18%). However, the percentage of papers on hESCs and iPSCS with a California author rose from zero in 1998 and 2006 (the year each was discovered) to a high of 45 percent in 2009. That has since dropped down a little but still remains consistently high.

Study graphic study code The article says the reason for this is really rather obvious: “that state funding programs appear to have contributed to over-performance in the field.”

“After the California Institute for Regenerative Medicine (CIRM) issued its first grants in April 2006, the share of articles acknowledging California funding increased rapidly. Between 2010 and 2013, approximately 55% of hESC-related articles published with at least one California author acknowledged state funding, suggesting that this funding program played an important role as California maintained and built upon its early leadership in the field.”

Connecticut also saw its share of publications rise, though not as dramatically as California. Maryland and New York, in contrast, saw their share of publications remain consistent. However, as the researchers point out, with California gobbling up so much more of the available space in these journals, the fact that both states kept their share consistent was an achievement in itself.

The researchers acknowledge that scientific publications are “only one measure of the impact of state science programs” and say it’s important we look at other measures as well – such as how many clinical trials arise from that research. Nonetheless they conclude by saying:

“This analysis illustrating the relative performance of states in the production of stem-cell-related research publications provides a useful starting point for policymakers and, potentially, voters considering the future of state stem cell funding efforts as well as others interested in state science and technology policy more generally.”

‘STARS’ Help Scientists Control Genetic On/Off Switch

All life on Earth relies, ultimately, on the delicate coordination of switches. During development, these switches turn genes on—or keep them off—at precise intervals, controlling the complex processes that guide the growth of the embryo, cell by cell, as it matures from a collection of stem cells into a living, breathing organism.

Scientists have found a new way to control genetic switches.

Scientists have found a new way to control genetic switches.

If you control the switch, you could theoretically control some of life’s most fundamental processes.

Which is precisely what scientists at Cornell University are attempting to do.

Reporting in today’s issue of Nature Chemical Biology, synthetic biologists have developed a new method of directing these switches—a feat that could revolutionize the field of genetic engineering.

At the heart of the team’s discovery is a tiny molecule called RNA. A more simplified version of its cousin, DNA, RNA normally serves as a liaison—translating the genetic information housed in DNA into the proteins that together make up each and every cell in the body.

In nature, RNA does not have the ability to ‘turn on’ a gene at will. So the Cornell team, led by Julius Lucks, made a new kind of RNA that did.

They engineered a new type of RNA that they are calling Small Transcription Activating RNAs, or STARS, that can serve as a kind of artificial switch. In laboratory experiments, Lucks and his team showed that they could control how and when a gene was switched on by physically placing the STARS system in front of it. As Lucks explained in a news release:

“RNA is like a molecular puzzle, a crazy Rubik’s cube that has to be unlocked in order to do different things. We’ve figured out how to design another RNA that unlocks part of that puzzle. The STAR is the key to that lock.”

RNA is an attractive molecule to manipulate because it is so simple, says Lucks, much simpler than proteins. Many efforts aimed at protein manipulation have failed, due to the sheer complexity of these molecules. But by downshifting into the simpler, more manageable RNA molecules, Lucks argues that greater strides can be made in the field of synthetic biology and genetic engineering.

“This is going to open up a whole set of possibilities for us, because RNA molecules make decisions and compute information really well, and they detect things really well,” said Lucks.

In the future, Lucks envisions a system based solely on RNA that has the capability to manipulate genetic switches to better understand fundamental processes that guide the healthy development of a cell—and provide clues to what happens when those processes go awry.

Stem cell stories that caught our eye: new ways to reprogram, shifting attitudes on tissue donation, and hockey legend’s miracle questioned

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.

Insulin-producing cells produced from skin. Starting with human skin cells a team at the University of Iowa has created iPS-type stem cells through genetic reprogramming and matured those stem cells into insulin-producing cells that successfully brought blood-sugar levels closer to normal when transplanted in mice.

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left). [Credit: University of Iowa]

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left).
[Credit: University of Iowa]

The cells did not completely restore blood-sugar levels to normal, but did point to the possibility of achieving that goal in the future, something the team leader Nicholas Zavazava noted in an article in the Des Moines Register, calling the work an “encouraging first step” toward a potential cure for diabetes.

The Register discussed the possibility of making personalized cells that match the genetics of the patient and avoiding the need for immune suppression. This has long been a goal with iPS cells, but increasingly the research community has turned to looking for options that would avoid immune rejection with donor cells that could be off-the-shelf and less expensive than making new cells for each patient.

Heart cells from reprogramming work in mice. Like several other teams, a group in Japan created beating heart cells from iPS-type stem cells. But they went the additional step of growing them into sheets of heart muscle that when transplanted into mice integrated into the animals own heart and beat to the same rhythm.

The team published the work in Cell Transplantation and the news agency AlianzaNews ran a story noting that it has previously been unclear if these cells would get in sync with the host heart muscle. The result provides hope this could be a route to repair hearts damaged by heart attack.

Patient attitudes on donating tissue. A University of Michigan study suggests most folks don’t care how you use body tissue they donate for research if you ask them about research generically. But their attitudes change when you ask about specific research, with positive responses increasing for only one type of research: stem cell research.

On the generic question, 69 percent said go for it, but when you mentioned the possibility of abortion research more than half said no and if told the cells might lead to commercial products 45 percent said nix. The team published their work in the Journal of the American Medical Association and HealthCanal picked up the university’s press release that quoted the lead researcher, Tom Tomlinson, on why paying attention to donor preference is so critical:

“Biobanks are becoming more and more important to health research, so it’s important to understand these concerns and how transparent these facilities need to be in the research they support.”

CIRM has begun building a bank of iPS-type stem cells made from tissue donated by people with one of 11 diseases. We went through a very detailed process to develop uniform informed consent forms to make sure the donors for our cell bank knew exactly how their cells could be used. Read more about the consent process here.

Mainstream media start to question hockey legend’s miracle. Finally some healthy skepticism has arrived. Hockey legend Gordie Howe’s recovery from a pair of strokes just before the holidays was treated by the general media as a true Christmas miracle. The scientific press tried to layer the coverage with some questions of what we don’t know about his case but not the mainstream media. The one exception I saw was Brad Fikes in the San Diego Union Tribune who had to rely on a couple of scientists who were openly speaking out at the time. We wrote about their concerns then as well.

Now two major outlets have raised questions in long pieces back-to-back yesterday and this morning. The Star in hockey-crazed Canada wrote the first piece and New York Magazine wrote today’s. Both raise serious questions about whether stem cells could have been the cause of Howe’s recovery and are valuable additions to the coverage.