Stem cell stories that caught our eye; cystic fibrosis, brain repair and Type 2 diabetes

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.

“Organoids” screen for cystic fibrosis drugs
. Starting with iPS-type stem cells made by reprogramming skin cells from cystic fibrosis (CF) patients a team at the University of Cambridge in the U.K. created mini lungs in a dish. These organoids should provide a great tool for screening drugs to treat the disease.

The researchers pushed the stem cells to go through the early stages of embryo development and then on to become 3-D distal airway tissue, the part of the lung that processes gas exchange. They were able to use a florescent marker to show an aspect of the cells’ function that was different in cells from CF patients and those from normal individuals. When they treated the CF cells with a drug that is being tested in CF patients, they saw the function correct to the normal state.

Bioscience Technology
picked up the university’s press release about the work published in the journal Stem Cells and Development. It quotes the scientist who led the study, Nick Hannon, on the application of the new tool:

“We’re confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis.”

To repair a brain knock its “pinky” down. A team at the University of California, San Francisco, has discovered a molecule that when it is shut down nerve stem cells can produce a whole lot more nerves. They call the molecule Pnky, named after the cartoon Pinky and the Brain.

Pinky_and_the_Brain_vol1Pkny belongs to a set of molecules known as long noncoding RNAs (lncRNAs), which researchers are finding are more abundant and more important than originally thought. The most familiar RNAs are the intermediary molecules between the DNA in our genes and the proteins that let our cells function. Initially, all the noncoding RNAs were thought to have no function, but in recent years many have been found to have critical roles in determining which genes are active. And Pnky seems to tamp down the activity of nerve stem cells. In a university press release picked up by HealthCanal Daniel Lim, the head researcher explained what happens when they shut down the gene:

“It is remarkable that when you take Pnky away, the stem cells produce many more neurons. These findings suggest that Pnky, and perhaps lncRNAs in general, could eventually have important applications in regenerative medicine and cancer treatment.”

Lim went onto explain the cancer connection. Since Pnky binds to a protein found in brain tumors, it might be involved in regulating the growth of brain tumors. A lot more work needs to happen before that hunch—or the use of Pnky blockers in brain injury—can lead to therapies, but this study certainly paints an intriguing path forward.

Stem cells and Type 2 diabetes. A few teams have succeeded in using stem cells to produce insulin-secreting tissue to correct Type 1 diabetes in animals, but it has been uncertain if the procedure would work for Type 2 diabetes. Type 1 is marked by a lack of insulin production, while resistance to the body’s own insulin, not lack of insulin, is the hallmark of type 2. A team at the University of British Columbia has new data showing stem cell therapy may indeed have a place in treating Type 2.

In mice fed a high fat diet until they developed the symptoms of Type 2 diabetes the stem cell-derived cells did help, but they did not fully correct the metabolism of the mice until they added one of the drugs commonly used to treat diabetes today. The drugs alone, also did not restore normal metabolism, which is often the case with human Type 2 diabetics.

The combination of drugs and cells improved the mice’s sugar metabolism, body weight and insulin sensitivity. The research appeared in the journal Stem Cell Reports and the University’s press release was picked up by several outlets including Fox News.

They transplanted cells from humans and even though the mice were immune suppressed, they took the added measure of protecting the cells in an encapsulation device. They noted that this would be required for use in humans and showing that it worked in mice would speed up any human trials. They also gave a shout out to the clinical trial CIRM funds at Viacyte, noting that since the Food and Drug Administration has already approved use of a similar device by Viacyte, the work might gain more rapid approval.

Stem cell stories that caught our eye; drug screening, aging stem cells in brain repair and blood diseases

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.

Heart-on-a-chip used to screen drugs. With CIRM funding, a team at the University of California, Berkeley, has used stem cell technology to create a virtual heart on an inch-long piece of silicon. The cells in that “chip” mimic the physiology of a human heart and have shown that they can accurately show how drugs will impact the heart.
HeartChip4196107801
Starting with iPS-type stem cells made from reprogramming adult cells the researchers grew them into heart muscle that could beat and align in multiple layers with microscopic channels that mimic blood vessels. They tested three drugs currently used to treat heart disease and found the changes seen in the heart-on-a-chip were consistent with what is seen in patients. For example, they tested isoproterenol, a drug used to treat slow heart rate and saw a dramatic increase in heart rate.

But the real value in the silicon-housed heart will be in screening potential new drugs and finding out adverse impacts before taking them into costly human clinical trials. Genetic Engineering & Biotechnology News wrote up the work and quoted a member of the team, Kevin Healy:

“It takes about $5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market.”

Brain stem cell activity decreases with age. We have known for some time that the adult stem cells that reside in most of our tissues and spend our lives repairing those tissues are less effective as we age. But the stemness of those cells—their ability to regenerate themselves—has not generally been questioned, rather we have assumed they just lost some of their ability to mature into the type of cell needed to make the repair.

Now, a team at the Ludwig-Maximilians-Universitat in Munich has published data suggesting that brain stem cells over time loose both their ability to renew themselves and some of their ability to become certain kinds of nerves. ScienceDaily picked up a press release from the institution and it quoted one of the authors, Magdalena Gotz, on the implications of their finding for therapy.

“In light of the fact that the stem cell supply is limited, we must now also look for ways to promote the self-renewal rate of the stem cells themselves and maintain the supply for a longer time.”

Another alternative for correcting genetic blood disease. CIRM funds a few programs that are trying to treat blood diseases such as sickle cell anemia and beta thalassemia by genetically altering blood forming stem cells. The goal being to correct defects in the gene for hemoglobin, the protein that carries oxygen in red blood cells.

Instead of starting with a patient’s own blood stem cells, which can require a somewhat traumatic harvest procedure, a new approach by a team at the Salk Institute in La Jolla creates iPS type stem cells by reprogramming the cells in a small skin sample. They mature those into blood stem cells and genetically modify them so that they can produce red blood cells that have the correct hemoglobin.

The Salk team uses a modified cold virus to carry the gene into the cell. ScienceDaily picked up the institute’s press release, which quotes one of the co-first authors on the study Mo Li on how the process works:

“It happens naturally, working like a zipper. The good gene just zips in perfectly, pushing the bad one out.”

CIRM funds other work by the senior author, Juan Carlos Izpisua Belmonte, but not this project. Because you never know which technology is going to work out best in the long term, it is nice to see other funders stepping up and pushing this alternative forward.

Heroic three-year study reveals safe methods for growing clinical-grade stem cells

Imagine seeking out the ideal pancake recipe: should you include sugar or no sugar? How about bleached vs. unbleached flour? Baking power or baking soda? When to flip the pancake on the skillet? You really have to test out many parameters to get that perfectly delicious light and fluffy pancake.

Essentially that’s what a CIRM-funded research team from both The Scripps Research Institute (TSRI) and UC San Diego accomplished but instead of making pancakes they were growing stem cells in the lab. In a heroic effect, they spent nearly three years systematically testing out different recipes and found conditions that should be safest for stem cell-based therapies in people. Their findings were reported today in PLOS ONE.

stem cells 2

Pluripotent stem cells. Courtesy of Andres Bratt-Leal from Jeanne Loring’s laboratory.

Let’s step back a bit in this story. If you’re a frequent reader of The Stem Cellar you know that one of the reasons stem cells are such an exciting field of biology is their pluripotency. That is, these nondescript cells have the capacity to become any type of cell in the body (pluri= many; potency = potential). This is true for embryonic stem cells and induced pluripotent cells (iPS). Several clinical trials underway or in development aim to harness this shape-shifting property to return insulin producing cells to people living with diabetes or to restore damaged nerves in victims of spinal cord injury, to name just two examples.

The other defining feature of pluripotent stem cell is their ability to make copies of themselves and grow indefinitely on petri dishes in the laboratory. As they multiply, the cells eventually take up all the real estate on the petri dish. If left alone the cells exhaust their liquid nutrients and die. So the cells must regularly be “passaged”; that is, removed from the dish and split into more dishes to provide new space to grow. This is also necessary for growing up enough quantities of cells for transplantation in people.

Previous small scale studies have observed that particular recipes for growing pluripotent cells can lead to genetic instability, such as deletion or duplication of DNA, that is linked with cancerous growth and tumor formation. This is perhaps the biggest worry about stem cell-based transplantation treatments: that they may cure disease but also cause cancer.

To find the conditions that minimize this genetic instability, the research team embarked on the first large-scale systematic study of the effects of various combinations of cell growth methods. One of the senior authors Louise Laurent, assistant professor at UC San Diego, explained in a press release the importance of this meticulous, quality control study:

“The processes used to maintain and expand stem cell cultures for cell replacement therapies needs to be improved, and the resulting cells carefully tested before use.”

To seek the ideal recipe, the team tested several parameters. For example, they grew some cells on top of so-called “feeder cells”, which help the stem cells grow while other cells used feeder-free conditions. Two different passaging methods were examined: one uses an enzyme solution to strip the cells off the petri dish while in the other method the cells are manually removed. Different liquid nutrients for the cell were included in the study as well. The different combinations of cells were grown continuously through 100 passages and changes in their genetic stability were periodically analyzed along the way.

loring_jeanne

Jeanne Loring (above) is professor of developmental neurobiology at TSRI and senior author of the study with Louise Laurent of the University of California, San Diego.

The long-term experiment paid off: the team found that the stem cells grown on feeder free petri dishes and passaged using the enzyme solution accumulated more genetic abnormalities than cells grown on feeder cells and passaged manually. The team also observed genetic changes after many cells passages. In particular, a recurring deletion of a gene called TP53. This gene is responsible for making a protein that acts to suppress cancers. So without this suppressor, later cell passages have the danger of becoming cancerous.

Based on these results, the other senior author, Jeanne Loring, a professor of developmental neurobiology at TSRI, gave this succinct advice:

“If you want to preserve the integrity of the genome, then grow your cells under those conditions with feeder cells and manual passaging. Also, analyze your cells—it’s really easy.”

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.

shutterstock_93075775

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.”

Stem cell stories that caught our eye: Cancer genetics, cell fate, super donors and tale of road to diabetes cure

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.

For cancer growth timing is everything. A study originating at the University of Southern California suggests tumors are born to be bad. Mutations constantly occur during the life of a tumor but those that occur early on determine if a tumor will grow as a benign mass of a cancerous one that spreads.

Describing the genetic markers the team found, the senior author, Christina Curtis, who recently moved to Stanford, was quoted in a story in ScienceBlog:

“What you see in the final cancer was there from the beginning.”

The CIRM funded team completed detailed genetic analysis of tumor cells surgically removed from colon cancer patients. Doctors treating these patients have long been hampered by an inability to tell which tumors will remain small and benign and which will develop into full-blown cancer. The researchers suggest the genetic fingerprints they have uncovered could lead to improved diagnosis for patients.

Physical forces also key to cell fate.
Putting the squeeze on stem cells may be what’s needed to get them to become bone. In this case, a team at the University of California, San Diego, used teeny tiny tweezers called “optical tweezers,” to trigger key internal signals that directed stem cells to go down the path to bone.

Pressure results in release of a cell signal shown in red

Pressure results in release of a cell signal shown in red

We have frequently written about the tremendous importance of a stem cell’s environment—its neighborhood if you will—in determining its fate. Yingxiao Wang, who led the study, described this role in a press release from the university picked up by ScienceNewsline:

“The mechanical environment around a stem cell helps govern a stem cell’s fate. Cells surrounded in stiff tissue such as the jaw, for example, have higher amounts of tension applied to them, and they can promote the production of harder tissues such as bone.”

He said the findings should help researchers trying to replicate the natural stem cell environment in the lab when they try to grow replacement tissues for patients.

Super donors could provide matching tissue.
One of the biggest challenges of using stem cells to replace damaged tissue is avoiding immune system rejection of the new cells. CIRM-grantee Cellular Dynamics International (CDI) announced this week that they have made key initial steps to creating a cell bank that could make this much easier.

Our bodies use molecules on the surface of our cells to identify tissue that is ours versus foreign such as bacteria. The huge variation in those molecules, called HLA, makes the matching needed for donor organ, or donor cells, more difficult than the New York Times Sunday crossword. But a few individuals posses an HLA combination that allows them to match to a large percent of the population.

CDI has now created clinical grade stem cell lines using iPS reprogramming of adult tissue from two such “super donors.” Just those two cell lines provide genetic matches for 19 percent of the population. The company plans to develop additional lines from other super donors with the goal of creating a bank that would cover 95 percent of the population.

Reuters picked up the company’s press release. CIRM does not fund this project, but we do fund another cell bank for which CDI is creating cells to better understand the causes of 11 diseases that have complex genetic origins

Narrative tells the tale of developing diabetes therapy. MIT Technology Review has published a well-told feature about the long road to creating a stem cell-based therapy for diabetes. Author Bran Alexander starts with the early days of the “stem cell wars” and carries the tale through treatment of the first patients in the CIRM-funded clinical trial being carried out by ViaCyte and the University of California, San Diego.

The piece quotes Viacyte’s chief scientific officer Kevin D’Amour about the long road:

“When I first came to ViaCyte 12 years ago, cell replacement through stem cells was so obvious. We all said, ‘Oh, that’s the low-hanging fruit.’ But it turned out to be a coconut, not an apple.”

But the article shows that with Viacyte’s product as well as others coming down the pike, that coconut has been cracked and real hope for diabetics lies inside.

Stem cell stories that caught our eye: repairing radiation damage, beta thalassemia clinical trial and disease models

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 cells repair brain damage from radiation therapy. Radiation for brain cancer can be a lifesaver but it can also be a dramatic life changer. If often leaves patients with considerably reduced brain function. Now a team at New York’s Memorial Sloan Kettering Cancer Center has found a way to instruct human stem cells to repair some of that damage—at least in rats.

The damage seems to be to the middle-man or so-called progenitor cells that maintain the myelin cells that insulate the nerves in the brain. When that myelin is damaged by the radiation those progenitor cells are no longer able to make repairs and that results in reduced nerve function. Rats given the stem cells regained both cognitive and motor skills lost after brain radiation.

The team leader, Viviane Taber, noted this work could make radiation therapy even more of a lifesaver. ScienceDaily quoted Tabar from materials provided by Cell Press that published the work:

“This will have to be proven further, but if we can repair the brain effectively, we could be bolder with our radiation dosing, within limits.”

This could be especially important in children, for whom physicians deliberately deliver lower radiation doses.


Stem cell trial for Beta-Thalassemia cleared to begin.
CIRM-grantee Sangamo BioSciences announced this week that the Food and Drug Administration (FDA) had accepted its application to begin a clinical trial using genetically edited stem cells to treat patients with beta-thalassemia. This trial, in patients who require regular blood transfusions to survive, is the ninth CIRM-funded clinical trail to gain clearance from the FDA.

Other clinical trials have used genetically modified stem cells, but they have used various techniques to add a correct gene or silence an unwanted gene. This will be the first clinical trial using one of the newer techniques that actually goes into a person’s genes and edits them to correct a disease. We wrote about this beta-thalassemia project here.

The Sacramento Business Times picked up the company’s press release that quoted Sangamo president Edward Lanphier on the company’s goal, “the aim of providing transfusion-dependent beta-thalassemia patients with a one-time treatment for this devastating disease.”

Disease modeling for science wonks. Vivien Marx wrote a feature article for Nature Methods that provides the most thorough review of the use of reprogramed iPS-type stem cells as disease models that I have read. In particular she discusses the power of using new gene editing tools to modify the cells so that when they mature into adult tissues they will display specific disease traits.

Svendsen hopes to use gene-edited iPS type stem cells to fully understand neurodegenerative diseases

Svendsen hopes to use gene-edited iPS type stem cells to fully understand neurodegenerative diseases

She starts with a narrative about CIRM-grantee Clive Svendsen’s work to understand spinal muscular atropohy (SMA) when he was in Wisconsin and to understand amyotrophic lateral sclerosis (ALS) now at Cedars Sinai in Los Angeles. She goes on to show just how powerful these gene-edited stem cells can be, but also how difficult it is to use the technology in a way that generates useful information. Marx is a strong science journalist, who for many years has shown a skill at explaining complex technologies.

She also discusses the various iPS cell banks developed around the world including CIRM’s cell bank and the value of having non-gene-edited cells from patients that naturally show the disease traits.

Thorough review of changes at CIRM.
Alex Lash at xconomy wrote an in-depth overview of our president Randy Mills’ plans for the next phase of our agency that Randy calls CIRM 2.0. Calling the plans an extensive “renovation” Lash described the portions of the new structure that were already in place and listed the ones set to come online in the next six months.

As a balanced journalist he runs through some of the highs and lows of our public perception during the initial phase of the agency and then discusses the new tone set by Mills:

“CIRM is less a grant-making government agency than a ‘discerning investor’ that’s going to be ‘as creative and innovative’ as possible in getting treatments approved, Mills says. ‘We have no mission above accelerating stem cell therapies to patients.’ ”

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.

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.

CIRM-funded scientists track the steps that take an adult cell back in time

The ability to transform an adult cell back into a stem cell has been heralded as one of the greatest achievements of the 21st century. Scientists have lauded this discovery, made by Nobel Prize-winning scientist Shinya Yamanaka, as a game changer for the future of medicine.

Despite this extraordinary advance, the method remains inefficient. And even the top experts still don’t quite understand how it works.

But now, a team of stem cell scientists from the University of California, Los Angeles (UCLA) has mapped the precise series of steps that an adult skin cell must go through to become a stem cell. The results, published online in the journal Cell, represent a much-needed step towards bringing cellular reprogramming forward.

A colony of iPSC's obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

A colony of iPSC’s obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

In this study, co-first authors Vincent Pasque and Jason Tchieu initiated the reprogramming process, whereby adult cells are reprogrammed back into embryonic-like stem cells. Yamanaka called these cells induced pluripotent stem cells, or iPSCs.

In order to map the steps being taken to reprogram these cells, the team devised a detailed time-course analysis whereby they would observe and analyze the cells each day as they transformed over a period of two weeks.

Importantly, the team found that no matter what type of adult cells were involved, the specific steps it took during reprogramming were the same. This revelation, that all adult cell types follow the same road map, is one of the most exciting discoveries. Said Pasque in a news release:

“The exact stage of reprogramming of any cell can now be determined. This study signals a big change in our thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner.”

The research team, led by CIRM grantee Katherin Plath, also uncovered some interesting information about the sequence of steps taken by these reprogrammed cells.

When an adult cell is reprogrammed back into an iPSC, it is not simply that all the steps that normally take an embryonic stem cell into an adult cell are reversed. Some may be reversed in the correct order, but others are not. And some steps are put off until the very end—indicating strong resistance against reprogramming.

“This reflects how cells do not like to change from one specialized cell type into another and resist a change in cellular identity,” said Pasque.

With future work, the team hopes to continue to investigate the reprogramming process. They are also hopeful that this newfound insight will bring robust iPSC-based therapies to the clinic.

Peering inside the brain: how stem cells could help turn skin into therapies for dementia

To truly understand a disease you need to be able to see how it works, how it causes our body to act in ways that it shouldn’t. In cancer, for example, you can take cells from a tumor and observe them under a microscope to see what is going on. But with diseases of the brain it’s much harder. You can’t just open someone’s skull to grab some cells to study. However, now we have new tools that enable us to skip the skull-opening bit, and examine brain cells in people with diseases like dementia, to see what’s going wrong, and maybe even to get some ideas on how to make it right.

AF_neuronTHMito(2)_webThe latest example of this comes from researchers in Belgium who have developed a new strategy for treating patients with an inherited form of dementia. They used the induced pluripotent stem cell (iPSC) method, taking take skin cells from patients with frontotemporal dementia, and turning them into neurons, the kind of brain cell damaged by the disease. They were then able to study those neurons for clues as to what was happening inside the brain.

The study is reported in the journal Stem Cell Reports, and in an accompanying news release the senior author, Catherine Verfaillie, says this approach allows them to study problems in the brain in ways that weren’t possible before.

“iPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons.”

The researchers identified problems with a particular signaling pathway in the brain, Wnt, which plays an important role in the development of neurons. In patients with frontotemporal dementia, the neurons weren’t able to mature into cortical neurons, which play a key role in enabling thought, perception and voluntary movement. However, by genetically correcting that problem they were able to restore the ability of the neurons to turn into cortical neurons.

Philip Van Damme, a lead researcher on the project, says this may open up possible ways to treat the problem.

“Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration. Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia.”