Stem cell stories that caught our eye: sickle cell patient data, vaccine link to leukemia protection, faster cell analysis

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.

Good news from sickle cell clinical trial. It is always satisfying to report positive results from human clinical trials using stem cells even when we don’t fund the work. Bluebird Bio released the first data on a patient treated for sickle cell anemia using the same procedure the company had earlier used to get good outcomes for two patients with beta thalassemia.

Both diseases result from defects—though different defects—in the gene for hemoglobin, the protein our red blood cells use to carry needed oxygen. So, in both cases they use a modified, deactivated virus to carry a correct version of the gene into patients’ own blood-forming stem cells in the lab. They then re-infused those cells into the patients to provide a ready supply of cells able to make the needed protein.

In the sickle cell patient, after the transplant a third of his red cells were making the right protein and that was enough to wean him off blood transfusions that had been keeping him alive and prevented any further hospitalizations due to the disease. The company also announced that the two previously reported patients treated for beta thalassemia had continued to improve. Reuters ran a story on the new data.

CIRM funds a similar project about to begin treating patients for sickle cell disease (link to video), also using a viral vector but a somewhat different one, so it is reassuring to see viral gene carriers working without side effects.

Another reason to vaccinate, prevent leukemia. While it has been known for some time that infant vaccination seems to have driven down the rate of childhood leukemia, no one has known why. A CIRM-funded team at the University of California, San Francisco, thinks they have figured it out. Viral infections trigger inflammation and the production of enzymes in cells that cause genetic mutations that lead to the cancer.

They worked with Haemophilus influenza Type b (Hib) vaccine but suggest a similar mechanism probably applies to other viral infections, and correspondingly, protection from other vaccines. The senior author on the paper, Marcus Muschen, explained the process in a university press release posted at Press-News.org

“These experiments help explain why the incidence of leukemia has been dramatically reduced since the advent of regular vaccinations during infancy. Hib and other childhood infections can cause recurrent and vehement immune responses, which we have found could lead to leukemia, but infants that have received vaccines are largely protected and acquire long-term immunity through very mild immune reactions.”

Barcoding individual cells. Our skin cells all pretty much look the same, but in the palm of your hand there are actually several different types of cells, even a tiny scratch of the fingernail. As scientist work to better understand how cells function, and in particular how stem cells mature, they increasingly need to know precisely what genes are turned on in individual cells.

Both techniques use tiny channels to isolate individual cells and introduce beads with "bar codes."

Both techniques use tiny channels to isolate individual cells and introduce beads with “bar codes.”

Until recently, all this type of analysis blended up a bunch of cells and asked what is in the collective soup. And this did not get the fine-tuned answers today’s scientists are seeking. Numerous teams over the past couple years have reported on tools to get down to single-cell gene analysis. Now, two teams at Harvard have independently developed ways to make this easier. They both use a type of DNA barcode on tiny beads that gets incorporated into individual cells before analysis.

Allan Klein, part of one team based at the Harvard Medical School’s main campus, described why the work is needed in a detailed narrative story released by the school:

“Does a population of cells that we initially think is uniform actually have some substructure. What is the nature of an early developing stem cell? . . . How is [a cell’s] fate determined? “

Even Macosko who worked with the other team centered at the Broad Institute of Harvard and MIT, noted the considerable increase in ease and decrease in cost with the new methods compared to some of the early methods of single cell gene analysis:

“If you’re a biologist with an interesting question in mind, this approach could shine a light on the problem without bankrupting you. It finally makes gene expression profiling on a cell-by-cell level tractable and accessible. I think it’s something biologists in a lot of fields will want to use.”

The narrative provides a good example of what we called the “bump rate” when I was at Harvard Med. Good science often moves forward when scientists bump into each other, and with Harvard Medical faculty scattered at 17 affiliated hospitals and research institutes scattered across Boston and Cambridge we were always looking for ways to increase the bump rate with conferences and cross department events. Macosko and Klein found out they were both working on similar systems at a conference.

A hopeful sight: therapy for vision loss cleared for clinical trial

Rosalinda Barrero

Rosalinda Barrero, has retinitis pigmentosa

Rosalinda Barrero says people often thought she was rude, or a snob, because of the way she behaved, pretending not to see them or ignoring them on the street. The truth is Rosalinda has retinitis pigmentosa (RP), a nasty disease, one that often attacks early in life and slowly destroys a person’s vision. Rosalinda’s eyes look normal but she can see almost nothing.

“I’ve lived my whole life with this. I told my daughters [as a child] I didn’t like to go Trick or Treating at Halloween because I couldn’t see. I’d trip; I’d loose my candy. I just wanted to stay home.”

Rosalinda says she desperately wants a treatment:

“Because I’m a mom and I would be so much a better mom if I could see. I could drive my daughters around. I want to do my part as a mom.”

Now a promising therapy for RP, funded by the stem cell agency, has been cleared by the Food and Drug Administration (FDA) to start a clinical trial in people.

The therapy was developed by Dr. Henry Klassen at the University of California, Irvine (UCI). RP is a relatively rare, inherited condition in which the light-sensitive cells at the back of the retina, cells that are essential for vision, slowly and progressively degenerate. Eventually it can result in blindness. There is no cure and no effective long-term treatment.

Dr. Klassen’s team will inject patients with stem cells, known as retinal progenitors, to help replace those cells destroyed by the disease and hopefully to save those not yet damaged.

In a news release about the therapy Dr. Klassen said the main goal of this small Phase I trial will be to make sure this approach is safe:

“This milestone is a very important one for our project. It signals a turning point, marking the beginning of the clinical phase of development, and we are all very excited about this project.”

Jonathan Thomas, the Chair of our Board, says that CIRM has invested almost $20 million to help support this work through early stage research and now, into the clinic.

“One of the goals of the agency is to provide the support that promising therapies need to progress and ultimately to get into clinical trials in patients. RP affects about 1.5 million people worldwide and is the leading cause of inherited blindness in the developed world. Having an effective treatment for it would transform people’s lives in extraordinary ways.”

Dr. Klassen says without that support it is doubtful that this work would have progressed as quickly as it has. And the support doesn’t just involve money:

“CIRM has played a critical and essential role in this project. While the funding is extremely important, CIRM also tutors and guides its grantees in the many aspects of translational development at every step of the way, and this accelerates during the later pre-clinical phase where much is at stake.”

This is now the 12th project that we are funding that has been approved by the FDA for clinical trials. It’s cause for optimism, but cautious optimism. These are small scale, early phase trials that in many cases are the first time these therapies have been tested in people. They look promising in the lab. Now it’s time to see if they are equally promising in people.

Considering we didn’t really start funding research until 2007 we have come a long way in a short time. Clearly we still have a long way to go. But the news that Dr. Klassen’s work has been given the go-ahead to take the next, big step, is a hopeful sign for Rosalinda and others with RP that we are at least heading in the right direction.

One of our recent Spotlight on Disease videos features Dr. Klassen and Rosalinda Barrero talking about RP.

This work will be one of the clinical trials being tested in our new Alpha Stem Cell Clinic Network. You can read more about that network here.

International stem cell group offers much needed guidance for patients and families

Yesterday the International Society for Stem Cell Research launched a greatly expanded website for the public. While the site, “Closer Look at Stem Cells,” offers a broad overview of stem cell science, the group launched it out of concern stem cell treatments are being marketed by clinics around the world without appropriate oversight and patient protections in place.

closer look webThe design for the new site provides easy navigation that quickly gets you to brief outlines and opportunities for a bit more information one click down. Most important, the detail page often includes a bright yellow warning icon with messages like this:

“View clinics that offer the same cell treatment for a wide variety of conditions or diseases with extreme caution. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.”

I could buy several rounds at the pub if I had a dollar for every time I said something like that to a desperate patient or family member who called CIRM with questions.

With quick reads like “Nine things to know about stem cell treatments,” as well as a more in-depth patient handbook the site provides ample opportunities to get the level of information any individual wants. It offers clear explanations for the different phases of clinical trials and what to expect if you enter a clinical trial.

A task force of society members and staff produced the new site. The chair of the task force, Megan Munsie from Stem Cells Australia, noted some of the concerns that triggered the effort in the organization’s press release:

“Promising clinical trials are underway for many diseases and conditions, but most stem cell-based treatments are still in the future. We hope that the website will foster interest and excitement in the science, but also an understanding of the current limitations of stem cells as medicine and a healthy skepticism of clinics selling treatments.”

Hope mixed with a good dose of skepticism is always a good approach to a new field of science. Our web site also offers advice for things to consider if a person is contemplating going to a clinic offering an unproven therapy outside of a clinical trial.

Gene Therapy Beats Half-Matched Stem Cell Transplant in Side-by-Side Comparison to Treat ‘Bubble Baby’ Disease

If you are born with Severe Combined Immunodeficiency (SCID), your childhood is anything but normal. You don’t get to play with other kids, or be held by your parents. You can’t even breathe the same air. And, without treatment, you probably won’t live past your first year.

The bubble boy.  Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

The bubble boy. Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

This is the reality of SCID, also called “Bubble Baby” disease, a term coined in the 1970s when the only way to manage the disease was isolating the child in a super clean environment to avoid exposure to germs. The only way to treat the disorder was with a fully matched stem cell transplant from a bone marrow donor, ideally from a sibling. But as you may have guessed, finding a match is extraordinarily rare. Until recently, the next best option was a ‘half-match’ transplant—usually from a parent. But now, scientists are exploring a third, potentially advantageous option: gene therapy. Late last year, we wrote about a promising clinical trial from UCLA researcher (and CIRM Grantee) Donald Kohn, whose team effectively ‘cured’ SCID in 18 children with the help of gene therapy. Experts still consider a fully matched stem cell transplant to be the gold standard of treatment for SCID. But are the second-tier contenders—gene therapy and half-matched transplant—both equally as effective? Until recently, no one had direct comparison. That all changes today, as scientists at the Necker Children’s Hospital in Paris compare in the journal Blood, for the first time, half-matched transplants and gene therapy—to see which approach comes out on top. The study’s lead author, Fabien Touzot, explained the importance of comparing these two methods:

“To ensure that we are providing the best alternative therapy possible, we wanted to compare outcomes among infants treated with gene therapy and infants receiving partial matched transplants.”

So the team monitored a group of 14 SCID children who had been treated with gene therapy, and compared them to another group of 13 who had received the half-matched transplant. And the differences were staggering. Children in the gene therapy group showed an immune system vastly improved compared to the half-matched transplant group. In fact, in the six months following treatment, T-cell counts (an indicator of overall immune system health) rose to almost normal levels in more than 75% of the gene therapy patients. In the transplant group, that number was just over 25%. The gene therapy patients also showed better resilience against infections and had far fewer infection-related hospitalizations—all indictors that gene therapy may in fact be superior to a half-matched transplant. This is encouraging news say researchers. Finding a fully matched stem cell donor is incredibly rare. Gene therapy could then give countless families of SCID patients hope that their children could lead comparatively normal, healthy lives. “Our analysis suggests that gene therapy can put these incredibly sick children on the road to defending themselves against infection faster than a half-matched transplant,” explained Touzot. “These results suggest that for patients without a fully matched stem cell donor, gene therapy is the next-best approach.” Hear more about how gene therapy could revolutionize treatment strategies for SCID in our recent interview with Donald Kohn:

Avoiding drug trial tragedies: new stem cell-based test predicts dangerous drug toxicity

In 2006 Ryan Wilson, a healthy 20 year old Londoner, volunteered for a first-in-human clinical trial to help test the safety of a new drug, TGN1412, intended to treat rheumatoid arthritis and leukemia. The cash he’d get in exchange for his time would help fund his upcoming vacation.

Instead, he nearly died.

Screen Shot 2015-03-11 at 11.37.42 AM

The TGN1412 drug trial disaster got a lot of high profile news coverage in 2006. (image credit: BBC News)

Even though the drug amount injected in his body was 500 times lower than the dose found to be safe in animals, Wilson experienced a catastrophic immune reaction, called a cytokine storm, that led to heart, kidney and liver failure, pneumonia and the loss of his toes and three fingers to dry gangrene. The other five healthy volunteers were also severely injured.

TGN1412’s devastating effect was unfortunately missed in preclinical laboratory and animal studies prior to the human trial. Unlike the pills in your medicine cabinet which are made up of synthesized chemicals, TGN1424 belongs to a growing class of medicines called biologics which come from biological sources such as proteins, DNA, sugars and cells. There is a concern that once a biologic is injected in a patient, the immune system may mount a strong attack all over the body. If that happens, too many immune cells, or white blood cells, are activated and release proteins, called cytokines, which in turn activate more immune cells and the reaction spirals into a dangerous cytokine storm like in Ryan Wilson’s case.

Clearly this tragedy begs for tests that can better predict drug toxicity in humans well before the first trial participants step into the clinic. On Monday a research team from the Imperial College London reported in the journal FASEB that they have done just that using human blood stem cells.

The team’s novel test is not so different than previous ones. Both tests are carried out in a petri dish using two human cell types: white blood cells and endothelial cells, a component of blood vessels. Both tests are also designed to mimic the human immune system’s response to biologics by measuring the release of cytokines.

15MAR11_cytokinestormimages

Endothelial cells grown from blood stem cells. (credit: Imperial College London)

But the Imperial College London team’s test differs from others in one important way: both the white blood cell and endothelial cell types come from the same individual. First they collect a donor’s blood stem cells and specialize them into endothelial cells. Then white blood cells are also collected from the same donor.

The prior tests, on the other hand, rely on cells from two different donors. Because the two cell types aren’t necessarily tissue-matched, the white blood cells may already be primed for an immune response even before a biologic is added to the test. In fact, these prior tests weren’t able to distinguish between a biologic known to cause a limited immune response versus TGN1424, known to cause a cytokine storm. The newly developed test, however, accurately predicts both the toxic cytokine storm caused by TGN1424 and the absence of a response by several approved biologics, such as the breast cancer drug Herceptin.

In a college news release, Jane Mitchell, the senior author on the report, sees the big picture importance of her lab’s work:

“As biological therapies become more mainstream, it’s more likely that drugs being tested on humans for the first time will have unexpected and potentially catastrophic effects. We’ve used adult stem cell technology to develop a laboratory test that could prevent another disaster like the TGN1412 trial.”

Their results also highlight the often-overlooked power of stem cells to not just deliver therapies but to help develop safer ones.

Pioneer’s 25-year struggle to treat blindness

Being a pioneer is never easy. You are charting unknown territory, tackling problems that have defeated others before you. You have to overcome so many obstacles that at times the challenge can seem insurmountable. But for those who succeed in reaching their goal, the rewards can be extraordinary.

Graziella Pellegrini, Center for Regenerative Medicine, University of Modena, Italy

Graziella Pellegrini, Center for Regenerative Medicine, University of Modena, Italy

Last month Italian researcher Graziella Pellegrini saw 25 years of work pay off when a treatment she developed to cure a form of blindness was given approval for sale by the European Commission.

This is quite an achievement as this means her treatment, called Holoclar, is among the first commercial stem therapies in the world (the first was Prochymal, which has been approved in Canada and New Zealand for the treatment of pediatric GVHD. This drug was developed by Osiris, which was led by our current President & CEO, Dr. Randy Mills.)

Holoclar uses stem cells to help stimulate the regrowth of a cornea. It can only be used for certain rare conditions, but that in no way diminishes its importance for patients or significance for the regenerative medicine field as a whole.

Nature recently sat down with Dr. Pellegrini to talk about her work, her struggle, and the many obstacles she had to overcome to get market approval for her work.

The interview makes for fascinating reading, and is a timely reminder why this kind of groundbreaking research never goes quite as quickly, or smoothly, as one would hope.

CIRM currently has a number of projects focused treating different causes of blindness on limbal cells (the kind Dr. Pellegrini worked on) and other forms of blindness; including a project to treat macular degeneration that has been approved for a clinical trial, and a therapy for retinitis pigmentosa that we hope will be approved for a clinical trial later this year.

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.

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.’ ”

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.