When it comes to scientific breakthroughs, are stem cells more like the internet or more like the much-hyped personal jet packs that never materialized?
In the late 1990s, it became possible for researchers to produce stem cells, which can develop into any type of specialized cell in the body. The advance inspired optimistic predictions that stem cells might be able to repair any body part that went on the fritz.
Bum knee? A quick shot of stem cells would give you a new supply of cartilage. Bad heart? Doctors would patch it up with stem cells — or even use the cells to produce a brand new heart in the lab.
But a decade and a half after scientists isolated the first embryonic stem cells and seven years after they first turned run-of-the-mill adult cells into stem cells, Americans with knee and heart problems are still getting artificial knees and pacemakers.
In fact, only a very narrow set of stem cell procedures have earned approval from the Food and Drug Administration (FDA). These blood cell-based treatments draw on the same medical knowledge that underpins bone marrow transplants, which were first successfully performed back when the Beatles topped the charts.
So what gives? According to experts, stem cells are still on track to bring about a revolution in medicine. The first wave of novel treatments will likely hit doctors' offices in the next 5 to 10 years, they say.
Turning Ideas into Treatments Takes Time
The two-decade wait may seem long for sick patients, but scientists say it’s on pace.
"It’s not slow in terms of truly novel treatments," said Dr. Ellen Feigal, senior vice president of research and development at the California Institute for Regenerative Medicine (CIRM), a state agency that is a major supporter of stem cell research.
Dr. Sean Morrison, president elect of the International Society for Stem Cell Research, has the frustrated air of someone who's been asked this same question many times.
“The public doesn’t understand how difficult it is to go from a promising idea to an actual new therapy,” he said. “It’s partly the fault of scientists who make breathless predictions — everybody wants to be positive and optimistic about things. Even when the idea is right, figuring out how to safely and effectively reduce it to a therapy is an extraordinarily difficult and time-consuming process."
That said, stem cell advocates and researchers are prepping for a victory lap in the coming years.
Ten stem cell-based research projects that CIRM has funded are now entering clinical trials, Feigal said. The treatments could have an outsized impact. One uses stem cells made to act as insulin-producing cells in the pancreas as a potential cure for Type 1 diabetes. Type 1 diabetes affects 5 percent of people with diabetes, or about 1.5 million Americans.
“Approaches are being tested in real, live patients who have real diseases and injuries, and that is happening now," Feigal said. “We expect to learn a lot in the next few years about what works and what doesn’t.”
Nationally, almost 2,000 clinical trials related to stem cells are ongoing, testing the cells’ effects on everything from advanced cancer to acidosis.
Treatments for heart failure, blindness, and broken bones are furthest along. But a seemingly miraculous cure for paralysis caused by spinal cord injuries may not be far behind, according to Morrison.
“If you’d asked me five years ago if we’d ever have a stem cell repair for spine injuries, I would have said I was pessimistic about that because it was too complicated a condition, but it’s an area of science that’s lurched ahead far more quickly than I ever imagined it would,” he said.
Scams Lure Sick Patients
Consumers could be forgiven for thinking that stem cell treatments are already available to cure whatever ails them.
Because stem cells hold so much promise, they’ve spurred a cottage industry of clinics that harvest and re-inject a patient’s own stem cells. These clinics make the claim that the treatment will alleviate everything from aging to rare diseases.
The procedure is legal because regulations don’t prohibit doctors from removing and re-injecting a patient’s own cells. But there’s no evidence to back their health claims.
“To capitalize on the general public’s sense of optimism about stem cells, there are snake oil clinics that have sprung up all over the world selling unproven therapies to unsuspecting patients,” Morrison said.
Most such clinics operate outside the United States, in countries with less oversight. But earlier this year, the FDA brought criminal charges against a doctor on the Texas-Mexico border for hawking stem cell transplants as a treatment for brain damage and amyotrophic lateral sclerosis (ALS).
It is to weed out these unscrupulous doctors that the FDA requires as much clinical research as it does before it approves new treatments.
“People complain about the FDA a lot, but the FDA protects the public from snake oil salesmen,” Morrison said.
Techniques Need Fine-Tuning
In addition to the time it takes for treatments to wind their way through the clinical trials system, there are big questions that have to be answered before man-made stem cells can deliver their promised cures.
Stem cells can potentially serve as a universal patch for any damaged body part, but doctors are finding that they must introduce them differently depending on where they want the patch to end up. Introducing stem cells into the bloodstream makes sense for patients who need a new supply of healthy blood cells, for example, but not for patients with ALS, whose troubles lie in the nervous system.
There are also quality control issues with manufactured, or induced, stem cells. Scientists will have to fine-tune their techniques for generating stem cells before the cells can safely form the basis of medicines. These induced stem cells are, for now, prone to growing into tumors.
“The [induced stem] cells don’t fully differentiate, and they’re not entirely normal. They don’t have the same mature function as the cells that we normally have in our body,” said Morrison.
Using Stem Cells to Approximate Organs
Even producing rough drafts of organs, as researchers can do now, can be useful.
Researchers can use stem cells from a patient who suffers from a rare or poorly understood disease with a genetic basis to study that disease. Because the stem cells share the patient’s DNA, they also develop the disease. The method goes by the unfortunately shorthand “disease in a dish,” and it gives researchers far better insight into disease behavior than they’ve ever had before.
“You can’t just biopsy somebody’s brain or their heart and then grow out lots of cells and do experiments to see 'Why does this guy’s brain not work like other people’s,' or 'Why do her heart muscle cells not beat properly under certain circumstances?,'” Morrison explained.
This kind of work is already in wide use, but it will be years before patients benefit.
“It’s too soon to point to examples where that work has helped patients. The path from that work to the clinic is at least 10 years,” Morrison said.
Stem cells crafted into a crude organ can also help screen new drug candidates. Liver or heart cells can be grown in a dish and then exposed to the new drug. If they don’t show signs of damage, that indicates that the drug won’t damage those organs in living patients. The prediction isn’t 100 percent accurate, but it’s a better indicator than a mouse’s response to the drug.
“We have every reason to believe that human cells will be better predictors than rodent cells,” said Feigal.
Better information on how a drug affects human patients could bring the multibillion-dollar cost of drug development down and head off issues of drug toxicity more quickly. That prospect has attracted the attention of the FDA.
Two in 10 drugs approved by the FDA are later pulled from the market when they prove more toxic than clinical trials showed; of those, 40 percent cause damage to the heart. The FDA is encouraging pharmaceutical companies and researchers to work together to develop an effective way to screen drugs for cardiac toxicity using human stem cells, according to Deok-Ho Kim, a University of Washington bioengineer who is working on the project.
But the cells aren't yet reliable enough to replace standard animal studies.
"It has great promise — it’s probably better than using the animal models — but it has technical challenges," said Kim.
Where’s My Custom Heart?
Stem cells’ biggest promise is that they will someday allow doctors to grow a whole replacement organ for a patient who would otherwise need a transplant.
Only a tiny fraction of patients who need heart transplants get them each year; there simply aren’t enough hearts to go around. Organs developed in the lab for individual patients could solve that problem. They would also free patients from taking anti-rejection drugs, which can have serious side effects.
A number of doctors and engineers are working on turning stem cells into the sophisticated architecture of a human organ. It’s not obvious how to get that basic structure right. The field is divided between scraping clean hearts from other animals before layering on human stem cells and putting stem cells into specially made three-dimensional printers.
"We see this coming decade as exploding with new types of approaches. The rubber hits the road here," said Feigal.
To create an organ, every stem cell must specialize exactly as needed — some cardiac cells must become heart muscle while others must become heart lining, for example. The different cells must arrange themselves just so. And, for a lab-grown organ to be given to a human patient, it would have to work at 100 percent capacity.
Simple body parts, including a trachea and a bladder, have been successfully created from stem cells and implanted in patients. Last year, researchers managed to get a miniature heart to beat, but it didn’t beat as strongly or with the same graceful synchronization as a human heart. Hearts and even kidneys ready for transplant remain a distant dream.
"I personally think there’s a long way to go," Kim said.