Stem cell therapy: Separating hope from hype

Of all the health topics in 2012, none has elicited more interest and excitement than stem cell treatments. Rhetoric had been plentiful, however, and separating it from fact had sometimes been a challenge. Today’s year-ender article for this column will hopefully help you separate fact from fiction and hope from hype, when it comes to stem cell therapy.

Scientists liken stem cells to seeds from which many body tissues grow. If these stem cells can be harnessed in healing body tissues, researchers say, they will result in dramatic improvements in our ability to treat even the most difficult and serious medical conditions. Embryonic stem cells — those derived from human embryos — hold special appeal because they can develop into any type of cell in the body. Two problems have, however, limited the potential of embryonic stem cells. First, there are ethical concerns about using human embryos for research, and second, there is a practical problem: if you need embryonic stem cells, you would ideally want your own genetically-identical cells. But your own embryonic stem cells only existed before your birth!

Then in 2006, a dramatic breakthrough was attained when a Japanese scientist, Shinya Yamanaka, discovered a surprisingly simple recipe, which can turn mature cells back into primitive cells, which in turn could be prodded into different kinds of mature cells. Yamanaka’s method provided a way to get such primitive cells (now known as induced pluripotent stem cells or iPS) without destroying embryos. These primitive cells were the equivalent of embryonic stem cells. Essentially, Yamanaka showed that you could turn back the clock! For this remarkable discovery, Yamanaka and British stem cell pioneer researcher John Gurdon were chosen as this year’s Nobel Prize awardees in Medicine.

Dr. David Scadden, co-director of the Harvard Stem Cell Institute, says, “iPS cells could solve the two big problems with embryonic stem cells. First, they could be generated without having to use an embryo, overcoming moral objections. And second, they would be genetically identical to you, making it less likely that your body would reject them. In fact, researchers are having success with iPS in experimental animals, using it to treat sickle cell anemia in mice and Parkinson’s disease in rats. But as exciting as it seems, what works on rodents doesn’t always work in humans.

“It will take a lot more work to be sure that iPS cells don’t cause adverse effects,” says Scadden. “Also, we’re not sure that iPS cells will find their way into a diseased organ deep in the body, and hook up with healthy cells in that organ to work in harmony with them. We still need to transform stem cell science into stem cell medicine!” Most studies on stem cell therapy, public or private, are just getting underway — at least in the US, so it is still too early to determine for sure the beneficial effects and long-term safety of stem cell therapy in various diseases and conditions.

Stem cell transplant

In fact, however, we do already have an example of a successful adult stem cell therapy — a blood stem cell transplant (sometimes called a bone marrow transplant). These transplants, which involve destroying cancerous bone marrow and replacing it with disease-free bone marrow stem cells, have been the standard of care for leukemia for decades now.

George Daley, director of stem cell transplantation at Children’s Hospital Boston, says bone marrow transplantation remains the only proven form of stem cell therapy. “Virtually everything else is highly experimental,” he adds. Even doctors working on FDA-approved stem cell clinical trials are still figuring out how to formulate treatments, deliver them effectively, and achieve maximum potency. Steve Sternberg, in a report on stem cells in USA Today in June last year, concluded: “Reliable therapy is years away…When patients agree to undergo unapproved stem cell therapies, they are taking a leap of faith, based on little more than the word of their doctors and the encouragement of other patients.”

Buyer, beware

“We’d all love easy miracles,” says Larry Goldstein, head of stem cell research at the University of California San Diego. “That’s not the way it works.” Daley adds, “On one hand, there are charlatans selling snake oil. At the other end of the spectrum are physicians who may be well-intentioned, but they’re misinformed if they’re giving patients stem cells before they’ve been proven to work.” Garry Green of UCLA sums it up: “It’s a case where the hype is ahead of the science.”

In spite of this, “Clinics are flourishing in the US, Mexico, China, India, the Dominican Republic, Thailand, Russia, and the United Kingdom, says Tim Caulfield, a University of Alberta, Canada, law professor, who has studied “direct-to-consumer” Internet marketing of stem cells. Caulfield’s team found that most websites play up the benefits and downplay the risks of stem cell therapy.  The average cost of care: just under US$50,000. Parents often fly their children to clinics for such ailments as autism and cerebral palsy. “It makes me angry,” he says. “They’re trading on the excitement of stem cells to market these therapies all over the world, for everything you can think of,” including autism, multiple sclerosis, blindness, heart disease, cancer, neurological disabilities — even aging! “I regard that as a marker for quackery. If they treat everything, you know it’s too good to be true.”

Guidelines

Many clinics that are offering stem cell treatments, both here and abroad, make claims about what stem cells can and cannot do that are not supported by present available scientific evidence. The International Society for Stem Cell Research (ISSCR), an academic group of researchers, scientists, and clinicians working in the field of stem cell science, offers the following information as guide to assist you in your decision-making regarding stem cell treatments:

There are different types of stem cells — each with their own purpose. Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell won’t spontaneously make a blood cell and vice versa. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve a different organ system. Be wary of clinics that offer treatment with stem cells that originate from a part of the body that is different from the part being treated.

A single cell treatment will not work on a multitude of unrelated diseases or conditions. Embryonic stem cells and iPS by themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when the treatments are offered for a wide variety of conditions but rely on a single cell type.

Currently, there are very few widely accepted stem cell therapies. The range of diseases where stem cell treatment has been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used, of course, is blood stem cell transplantation to treat diseases of the blood and immune systems, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.

Just because people say stem cells helped them doesn’t mean they did. Ted Kaptchuk of Harvard Medical School says he’s not surprised that some patients do actually appear to benefit from stem cell treatments. That’s not necessarily because the treatments work, he says. What matters is that the patients think they work. Kaptchuk says medical history is filled with studies in which sugar pills and sham surgery outperform the real thing, a phenomenon called the “placebo effect”. There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the “placebo effect,” accompanying treatments, and natural fluctuations of the disease or condition. These factors are so widespread that without testing in a controlled clinical study, where a group that received treatment is carefully compared against a group that does not receive the treatment, it is difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.

To be used in treatments, stem cells have to be instructed to behave in specific ways.  One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave exactly in the desired way that scientists and doctors would like them to. Consider that once transplanted inside the body, the cells need to integrate and function in concert with the body’s other cells. For example, to treat many neurological conditions, the cells we implant will need to grow into specific types of neurons, and to work, they will have to know which other neurons to make connections with, as well as how to make those connections. Researchers are still learning about how to direct stem cells to become the right cell type, to grow only as much as scientists wants them to, and the best ways to transplant them. Discovering how to do all these will take time. Be wary of claims that stem cells would somehow just know where to go and what to do to treat a specific condition.

There is something to lose by an unproven treatment. Some of the conditions that some stem cell clinics claim are treatable are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something, even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term. In one publicized case, as reported by ISSCR, a young boy developed brain tumors as a result of a stem cell treatment. So, it may not be completely risk-free! In the Philippine setting, stick to hospital-based clinics, where they have advance laboratory facilities and medical experts in stem cell therapy.

To summarize, before stem cell therapeutics can be applied more widely in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation, as well as the mechanisms of stem cell interaction with the diseased or damaged microenvironment. Stem cells do offer exciting promise for future therapies but significant technical hurdles remain that will only be overcome through years of intensive research.

Scientists around the world are continuing to research ways to harness stem cells and use them to learn about, to diagnose, and to treat, various diseases and conditions. Every day, scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials.

For example, in 2010, the British company ReNeuron announced it had been approved to conduct a Phase 1 clinical trial of a neural stem cell treatment for stroke. Likewise recently, a stem cell treatment for acute spinal cord injury has been authorized by the US FDA to move into Phase 1 clinical trial. Although sometimes it is hard to appreciate, stem cell science is moving forward slowly but steadily. Physicians are tremendously optimistic that stem cell therapies will someday be available to treat successfully a wide range of human diseases and conditions. When that time comes, it will truly revolutionize the whole practice of medicine and bring unimaginable progress in the treatment of many diseases that ail mankind!

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To all my faithful readers, early greetings for a Merry Christmas and a Happy and Healthy New Year!

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Sources: Stem Cell Institute, Harvard University; The US National Institutes of Health resource for stem cell research (http://stemcells.nih.gov/info/health); Steve Sternberg, “Doctors offer unapproved stem cell therapies,” USA Today, June 2011; and the International Society for Stem Cell Research (ISSCR).