Ten things patients should know when considering a stem cell treatment

If you’re a patient considering a treatment based on stem cells, check out this new Top 10 list from the International Society for Stem Cell Research first.

The ISSCR compiled this list of the “Top Ten Things to Know About Stem Cell Treatments” to counter some of the exaggerated claims being aggressively promoted on the Internet and in clinics. Here’s how ISSCR President Irv Weissman, a longtime stem cell researcher at Stanford University, put it in a press release:

Stem cells do hold tremendous promise for the treatment of many serious diseases. Yet there are organizations out there that are preying on patients’ hopes, offering stem cell treatments – often for large sums of money – for conditions where the current science simply does not support its benefit or safety.

The Top 10 list is designed to help patients tell whether a doctor of clinic is above-board. It explains what stem cells are and how they work. In doing so, it also explains why some of the claims being made today aren’t supported by science.

For instance, if a clinic says it can treat a variety of ailments using a single type of stem cell, that’s “a major warning sign." In addition, patients should “be wary” of clinics that say they can use stem cells from one part of the body and use them to treat another part.

The list also makes the useful points that patient testimonials are no substitute for rigorous scientific review, and that experimental treatments aren’t necessarily part of a clinical trial – especially when patients are asked to pay for them.

The ISSCR’s website includes a list of questions that patients should ask their doctors about stem cell treatments and videos from experts explaining why true stem cell therapies take so long to develop. If you’re curious about a particular clinic, you can even ask the ISSCR to review it.

-- Karen Kaplan

Photo: Clinics, like this one in Costa Rica, have come under fire for promoting unproven stem cell treatments to naive and desperate patients. Credit: Juan Carlos Ulate/Reuters

A stem cell booster from the supplements world: too good to be true?

Impressed with how well your (insert any nutritional supplement here) supports your metabolic function, your bone, brain, breast or prostate health, your energy level? The Journal of Translational Medicine -- an open-access publication of the respected British medical publisher BioMedCentral -- this week carries a study involving a natural-products concoction that might kick your nutritional supplement's butt. The study suggests that a product containing a fermented combination of green tea, astralagus, goji berry extracts and the kinds of live cultures found in yogurt significantly boosted circulating levels of the kinds of reparative stem cells produced by bone marrow.

Those stem cells play a key role in the body's effort to heal itself in the wake of tissue injury. But cancer doctors have known for decades they can also be mobilized and harvested, and used to rebuild the immune system of a patient who's undergone aggressive chemo and/or radiation therapy. To do that, either the patient herself or a matched stem-cell donor must undergo a course of medication -- "stimulating factor" -- to increase production of those hematopoietic stem cells and send them out into the bloodstream, where they can be captured.

But that medication is very costly, and its use over time can increase a person's risk of blood clots. Perhaps a cocktail of cheap ingredients found in plants and everyday foods could do the same thing more cheaply and safely? This study suggests there may be at least one that can.

"To our knowledge, this is the first study demonstrating profound mobilization effect with possible clinical significance by a food supplement-based approach," the authors wrote, after demonstrating that 14 days of supplementation with Stem-Kine, by several measures, increased production of hematopoietic stem cells and their appearance in the bloodstream of subjects. 

Too good to be true, as so many accounts of nutritional supplements are? It surely does not inspire confidence that the study was supported in part with a grant from the maker of the supplement, and that the lead author, who designed the experiment, interpreted data and prepared the manuscript, is a shareholder of the company that makes the stuff.

It also doesn't help that the authors acknowledge that "the mechanism" of this mobilization of stem cells "remains unknown" -- or that they don't openly wonder which of this busy cocktail's many ingredients might be active in affecting that mobilization.

But publication by BioMedCentral does confer some respectability on this study. So does the final line of the study: After suggesting that the nutritional supplement-stem cell link might "offer significant benefit in treatment of a wide variety of degenerative diseases," the authors write this: "Given commercial pressures associated with this largely unregulated field, we propose detailed scientific investigations must be made before disease-associated claims are made by the scientific community." 

-- Melissa Healy  

NIH seeks to expand the definition of 'human embryonic stem cell'

The National Institutes of Health is proposing a small change to the definition of “human embryonic stem cell” that could have a big effect on their long-term ability to lead to cures for a variety of diseases.

President Obama asked the NIH to come up with new guidelines for funding human embryonic stem cell (hESC) research, and those guidelines define the cells as ones that

“are derived from the inner cell mass of blastocyst stage human embryos, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.”

In plain English, that means that the cells come from embryos that are 4 to 6 days old, when they have grown into a ball of roughly 100 cells. Scientists in the lab can convert these cells into stem cells that retain the ability to grow into any type of tissue in the body, dismantling the embryo in the process.

But some researchers have complained that the definition was too restrictive. For instance, it would appear to exclude stem cells derived from younger embryos -- called blastomeres -- with only eight cells. It would even exclude embryonic stem cells derived from a single blastomere cell using the same biopsy technique employed for pre-implantation genetic diagnosis. This method has the advantage of producing human embryonic stem cells without destroying the human embryos they come from.

In a filing made Friday afternoon, the NIH acknowledged the problem with its original definition:

“This definition had the unintended consequence of excluding certain hESCs which may otherwise be appropriate for Federal funding. For example, the current definition excludes hESCs from an embryo which fails to develop to the blastocyst stage.”

So the agency proposes changing the definition of human embryonic stem cells to include

“pluripotent cells that are derived from early stage human embryos, up to and including the blastocyst stage, are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.”

The proposed change was published in the Federal Register. Members of the public can comment on the change at http://hescregapp.od.nih.gov/comments/add.htm before it takes final effect.

One stem cell researcher, Dr. Robert Lanza, has already voiced enthusiastic support for the change. His company, Advanced Cell Technology, has developed several cell lines from single blastomeres. One of those cell lines was used to grow retinal pigment epithelial cells that could treat patients with a rare eye disease called Stargardt’s macular dystrophy. The company asked the FDA for permission to conduct a Phase I/II clinical trial last year.

“It would have been a disaster to exclude these valuable hESC lines from consideration for federal funding, especially since the leftover embryos used to generate them meet all the NIH requirements," he said in an e-mail. " It shouldn’t matter what cells they were derived from. In fact, it could be strongly argued that these hESC lines are more ethical since they can be derived without embryo destruction."

-- Karen Kaplan 

Rodent of the Week: Mixing young blood with old

As we age, cells do not replicate as efficiently and lose their ability to repair damage. That leads to disease and physical decline. There is still no way to reverse aging, but researchers in Boston this week announced that it may be possible to use the blood of younger people to boost the healing powers of cells in older people.

The people part is still theoretical. But in mice, researchers at Harvard Stem Cell Institute and the Joslin Diabetes Center found that exposing old mice with the blood of younger mice caused their cells to start acting younger. The study, published in the journal Nature, suggests that a better understanding the body's blood-forming mechanisms may lead to treatments for age-related illnesses as well as stem-cell therapies.

In the study, researchers connected the circulatory systems of a young mouse and an older one so that the older animal was exposed to the blood of the younger one. They found that the blood-forming stem cells in the older animals functioned better, generating various types of blood cells in more appropriate ratios. Further, the study showed that bone-forming cells called osteoblasts play a key role in the process of blood stem cell maintenance and regeneration.

"What's most exciting is that the changes that occur in blood stem cells during aging are reversible through signals carried by the blood itself," Amy J. Wagers, the lead investigator of the study, said in a news release. "This means that the blood system offers a potential therapeutic avenue for age-related stem cell dysfunction."

In an article about the research in MIT Technology Review, writer Emily Singer points out that many questions remain about the research, including whether the older mice exposed to the younger-blood treatment will be more resistant to age-related ailments.

-- Shari Roan

Photo credit: Advance Cell Technology Inc.

Wounded soldier's shattered pancreas gets replaced in a whole new way

Six days before Thanksgiving, a 21-year-old Air Force enlistee, Tre Francesco Porfirio, was pulling duty in Afghanistan when three high-velocity bullets tore through his pancreas — the fist-size organ that produces insulin and enzymes we need to extract fuel from the food we eat.

With an injury like that, Porfirio's prognosis was very difficult: If he could survive long enough to get to a specialized transplant center, he could perhaps get a transplant of islet cells from a deceased donor and take anti-rejection drugs for the rest of his life. Or doctors could remove his pancreas, leaving him completely dependent on insulin. Either way, an early death from complications of Type 1 diabetes was highly likely.

But doctors who improvised a way to help the serviceman quickly made Porfirio a pioneer in the technique of islet-cell transplantation instead.

On Tuesday, Dr. Camillo Ricordi, director of the University of Miami's Diabetes Research Institute, told the story of a long-distance islet cell transplant — a still-experimental procedure considered to be the best hope for treating those, such as Type 1 diabetes patients, with a non-functioning pancreas. The transplant involved flying Porfirio's shattered pancreas — now removed — from an operating room at Walter Reed Army Medical Hospital in Washington to Ricordi's specialized laboratory, more than 1,000 miles away, at the University of Miami's Miller School of Medicine. There, on the night before Thanksgiving, the delicate islet cells of Porfirio's own pancreas were extracted and purified — a specialized operation performed at only a handful of transplant centers across the country.

Until now, if you were a patient who couldn't make it in time to one of 15 cities with medical centers equipped to prepare islet cells for transplant, you were out of luck. But physicians willing to try anything to help Porforio have shown that may no longer be true. 

The stew of islet cells prepared at the University of Miami was sent back to Walter Reed. There — under the supervision of Ricordi's team in Coral Gables, Fla., watching remotely — physicians carefully fed the purified cells through a tube into the airman's liver. Within days of the procedure, performed on Thanksgiving, Porfirio's islet cells did what all physicians hope they will do in such cases: They began to produce insulin, effectively doing the work of the excised pancreas.

Porfirio is unusual also in that his islet cells came from his own pancreas, which, while in shreds, was not dead yet. Most patients must rely on a deceased donor's pancreas and must take anti-rejection drugs to ensure their immune system doesn't attack the foreign cells. The ability to use Porfirio's own islet cells for the transplant, while "very rare," according to Ricordi, means he will not face rejection issues that make such transplants a lifelong challenge for recipients.

That remote transplant, said Ricordi in an interview, is a first: it could mean patients whose pancreas is destroyed by diabetes or trauma can be treated, potentially, anywhere in the country. Having shown that islet cells can be prepared for transplantation remotely and returned in time to a waiting patient — and then, that physicians with minimal training in such transplants can be supervised in doing them — Ricordi's team says that many more patients may gain access to the procedure. Patients with chronic pancreatitis, an inflammation of the insulin-producing organ, may, with some fancy logistics, be able to get the treatment they need close to home. And patients whose pancreas is compromised or destroyed by trauma can be treated where they are.

— Melissa Healy

New human embryonic stem cell lines eligible for federal research dollars for the first time since 2001

The number of human embryonic stem cell lines eligible to be used in government-funded research just went up by 13.

The National Institutes of Health announced today that 11 new cell lines from Dr. George Daley at Children’s Hospital Boston and two lines from Ali Brivanlou at Rockefeller University in New York became the first additions to the NIH Human Embryonic Stem Cell Registry since President Obama reversed his predecessor’s policy. Under President Bush, only human embryonic stem cells prior to August 2001 were eligible for federal funding.

The new lines were derived from embryos created for fertility treatments and donated by couples who went through a rigorous informed consent process.

And more may be on the way. The NIH said that 96 more lines have been submitted by researchers, including 20 that will be vetted by an advisory committee on Friday.

The additions come nearly nine months after Obama signed an executive order that directed the NIH to make federal research funds available to newer lines of human embryonic stem cells. Scientists were overjoyed and said the decision would accelerate the pace of research into such ailments as diabetes, Alzheimer's and spinal cord injuries. Details of the policy are available here.

-- Karen Kaplan

Photo: NIH Director Francis Collins said today that he was "happy to say that we now have human embryonic stem cell lines eligible for use by our research community under our new stem cell policy." Credit: Aude Guerrucci-Pool / Getty Images

Company seeks FDA permission to conduct clinical trial using human embryonic stem cells

Patients with a rare eye disease could be the first to be treated with human embryonic stem cells.

Advanced Cell Technology Inc., a Santa Monica-based biotech company with labs in Massachusetts, announced today that it has asked the U.S. Food and Drug Administration for approval to test retinal cells grown from stem cells in 12 people with Stargardt’s macular dystrophy.

The disease is a childhood version of macular degeneration and affects about one in 10,000 kids. Patients typically begin to lose their central vision between the ages of 6 and 20. As SMD progresses, things may look blurry and distorted, and patients may have trouble adjusting to low light. About half of victims are legally blind by age 50. There is no cure.

Most cases occur when children inherent a faulty version of the ABCA4 gene or the CNGB3 gene from both parents.  As a result, the photoreceptor cells in the retina don’t get enough fuel, and they atrophy.

ACT hopes to reverse this by supplying patients with new retinal pigment epithelium cells derived from human embryonic stem cells. The RPE cells have been shown to improve vision in animals, with one study restoring eye function in sick rats and mice to “near-normal” levels. Another study boosted rats’ vision to 70% that of healthy animals. No adverse side effects were found in any of the company’s pre-clinical studies, Dr. Robert Lanza, ACT’s chief scientific officer, said in an interview.

ACT proposes a Phase I/II trial designed to assess the safety and tolerability of its RPE cells. The company and its collaborators would like to recruit a dozen patients with advanced SMD at three sites: the Casey Eye Institute in Portland, Ore.; the University of Massachusetts Memorial Medical Center in Worcester; and the UMDNJ – New Jersey Medical School in Newark.

Amid much fanfare, Geron Corp. received FDA approval in January to use specialized nerve cells made out of human embryonic stem cells to treat a handful of patients paralyzed by spinal cord injuries. Those plans are on hold while the company conducts pre-clinical studies to address some safety concerns about its cells, known as GRNOPC1. Last month, Geron said it expected to initiate its clinical trial in the third quarter of 2010.

Since their creation in 1998, human embryonic stem cells have been a highly controversial area of medical research. The cells are derived from days-old human embryos, which gives them the ability to grow into any type of cell in the body. Some scientists – like those at ACT and Geron – envision using them to grow replacement tissues to treat sick patients. But many people are troubled by the fact that the stem cells are typically made by dismantling and destroying human embryos.

ACT has tried to sidestep the ethical debate by using a different method to create its stem cell lines. Instead of using an entire embryo, the company figured out a way to remove only a single blastomere cell from a three-day-old embryo and turn it into a cell line. Such single-cell biopsies are routinely performed in fertility clinics to screen embryos for devastating genetic diseases, and the procedure leaves the embryo intact. The RPE cells that would be used in the clinical trial were grown from one of the company’s single-blastomere cell lines, Lanza said.

The company is also making and testing RPE cells derived from induced pluripotent stem cells. So-called iPS cells behave like embryonic stem cells but are made by reprogramming mature cells taken from children or adults, not from embryos. However, the reprogramming process currently involves viruses and genetic manipulation techniques that make the cells unsuitable for human therapies.

Lanza said ACT decided to target Stargardt’s macular dystrophy first because it has been designated an “orphan disease” and could benefit from a faster regulatory review. The FDA has 30 days to respond to the company’s filing, made Wednesday, and the clinical trial could begin early next year.

If all goes well, the company plans to seek permission to use its RPE cells to treat age-related macular degeneration, Lanza said. That disorder is much more common, and it destroys the central vision of an estimated 1.75 million Americans.

-- Karen Kaplan

Photo: Scientists from Advanced Cell Technology remove a single cell from a days-old embryo, which was used to create a line of human embryonic stem cells. Stem cells made this way were grown into eye cells that the company hopes will treat patients with Stargardt's macular dystrophy. Credit: Associated Press photo/Advanced Cell Technology

A proposal for improving cord blood transplants

Roughly one in five hematopoietic stem cell transplants performed to treat blood disorders such as leukemia uses cord blood instead of the traditional bone marrow. Cord blood – harvested from umbilical cords shortly after birth – could be used more often if more of it were available. Nearly 14 million people worldwide have volunteered to donate their bone marrow, while the number of cord blood units available for transplant is just over 380,000.

Dutch researchers may have found a partial solution. In an article published in this week's edition of Proceedings of the National Academy of Sciences, they propose that a relatively simple change in the way donors are matched with recipients could expand the number of optimal matches by up to eighteenfold.

When patients need a bone marrow or cord blood transplant, they are matched with donors who share as many human leukocyte antigens (HLAs) as possible. The immune system checks these proteins to tell whether a cell belongs in the body or is foreign, so the closer the match, the greater the chance the transplant will take.

The researchers examined 1,121 patients who received a unit of cord blood from the New York Blood Center National Cord Blood Program. Only 62, or 6%, got blood that was HLA-matched. The remaining 1,059 patients got mismatched blood.

But by coincidence, 79, or 7%, got blood that was matched in another way – according to noninherited maternal antigens, or NIMAs. These are proteins that patients were exposed to from their mothers before they were born. As a result, the researchers speculated that patients with NIMA matches would tolerate their transplants better and have higher survival rates.

They were right.

Three years after their transplants, patients who didn’t have an HLA match but got NIMA-matched cord blood were 40% less likely to have died than patients who didn’t have either kind of match, according to the study. For the sake of comparison, patients who had an HLA match were 60% less likely to have died than patients without either kind of match.

The difference was especially pronounced in patients who were at least 10 years old. Compared with patients with no match, those with an HLA match were 70% less likely to have died and those with a NIMA match were 60% less likely to have passed away, the study found.

NIMA-matched blood had other benefits too. The transplants engrafted faster than in unmatched patients, and the incidence of graft-versus-host disease was lower. The benefits were greatest for patients who were expected to have the worst outcomes, the researchers reported.

The Dutch scientists said they intend to start using NIMA status to matching patients with cord blood and will track the results to see if these trends hold up. They urged others to do so as well.

Allowing patients to substitute one HLA-matched antigen for a NIMA-matched antigen would boost the number of possible matches by a factor of six, and allowing two substitutions would theoretically boost it as much as 18 times. The team calculated that even a sixfold increase in potential matches was the equivalent of increasing the number of cord blood units available for transplant to more than 2 million.

“Although much work lies ahead, our findings justify changing the match algorithm for CB [cord blood] transplants,” they wrote.

-- Karen Kaplan

Photo: A new matching technique could make the most of limited cord blood supplies. Credit: Los Angeles Times

Embryonic stem cells may restore brains damaged by radiation

Scientists at UC Irvine and UC San Francisco have found a potential new use for human embryonic stem cells – helping cancer patients recover the cognitive function lost when their brains are treated with radiation.

People with tumors in their head or neck often undergo radiation therapy after the cancer is surgically removed. That radiation helps kill off any malignant cells left behind. But it can also debilitate the region of the brain called the hippocampus, which is responsible for learning, memory and processing of spatial information. It is also one of only two areas in the brain known to produce new neurons.

The UC researchers wondered whether embryonic stem cells could pick up the slack. In their pluripotent state, they have the potential to grow into any type of cell in the body. When injected into the hippocampus, would they naturally replace neurons damaged or killed by radiation therapy?

To find out, they radiated the heads of 18 rats. Two days later, six of those rats got two injections of human embryonic stem cells directly into the hippocampus.

After four months, the researchers used a standard test to measure the rats’ cognitive abilities. They placed the animals in an arena with two Lego blocks – borrowed from the son of senior researcher Charles Limoli – and were allowed to explore for as long as they liked.  When they were done, the researchers took the rats out of the arena and moved one of the blocks. Five minutes later, the rats went back in.

All of the animals studied both of the blocks, but the rats that were treated with stem cells spent significantly more time nosing around the one that had been moved. They did so, the researchers say, because they remembered where it used to be and thus were curious about its new position. In fact, they spent almost as much time investigating the block as did a group of control rats that were never subjected to any radiation. But the radiated rats that didn’t get stem cells lost roughly half of their cognitive function, according to the study, published in this week's edition of Proceedings of the National Academy of Sciences.

The scientists tested the rats again 24 hours later and got similar – though less pronounced – results.

When the tests were over, the researchers euthanized the rats and studied their brains. Sure enough, the stem cells had grafted into the hippocampus, where they grew into neurons and another kind of brain cell called astrocytes. In the four months that they were in the rat brains, the stem cells didn’t appear to grow into tumors, though that might have happened if the rats lived longer.

The results suggest that embryonic stem cells could spare cancer patients much of the short-term memory loss that results from cranial radiation and perhaps boost long-term memory as well, the researchers wrote. But several hurdles would have to be cleared before it could be tried in people.

Instead of using embryonic stem cells – which many people object to because they are derived from embryos – patients could be treated with induced pluripotent stem cells. Better known as iPS cells, these reprogrammed cells have been found to behave almost exactly like embryonic stem cells in a variety of laboratory tests. They could be custom-made for cancer patients, reducing the risk that the stem cell transplants would be rejected. But more research is needed to ensure that they would not form new tumors.

“Any treatments showing promise at reversing this are worthy of pursuit,” Limoli, an associate professor of radiation oncology at UCI, said in a statement.

The experiments were funded by the National Institutes of Health and the California Institute for Regenerative Medicine.

-- Karen Kaplan

Photo: These human embryonic stem cells restored cognitive function to rats whose brains were damaged by radiation. Credit: Munjal Acharya / UCI

Rodent of the Week: How to mend a broken heart

The promise of stem-cell therapy is that researchers might be able to grow cells into specific tissue or organs that can replace or repair damaged parts. Researchers at Duke reported progress this week in developing a tissue patch that can be used for heart disease.

The scientists used mouse embryonic stem cells to grow a three-dimensional patch made up of heart muscle cells called cardiomyocytes. The tissue was able to contract and to conduct electrical impulses -- just like a real, beating heart. The patch, which looks like a piece of Chex cereal, was grown in biological substances, such as the blood-clotting protein fibrin and helper cells known as cardiac fibroblasts. These substances were crucial in coaxing the cells to grow in an organized manner that allowed them to function.

"When we tested the patch, we found that because the cells aligned themselves in the same direction, they were able to contract like native cells," a coauthor of the study, Brian Liau, said in a news release. "They were also able to carry the electrical signals that make cardiomyocytes function in a coordinated fashion."

More research is needed before heart patches could be used for humans with cardiovascular disease, Liau said. One of the major challenges is establishing a blood vessel supply to sustain the patch. The researchers will also test their model using non-embryonic stem cells. That could speed up the growth of the tissue since a human heart requires nine months for complete development. Moreover, if they could use a patient's own cells, it might prevent an immune system reaction.

The study was presented at the Biomedical Engineering Society annual meeting in Pittsburgh.

-- Shari Roan

Photo courtesy of Advanced Cell Technology Inc.