ST. LOUIS POST-DISPATCH
12/02/2007
There are breakthroughs, and then there are breakthroughs.
This one could be the medical equivalent of fire and the invention of the wheel.
Scientists are giddy about the news that researchers have learned how to reprogram skin cells to act like embryonic stem cells.
The cells could be some of the greatest tools modern medical science has ever devised.
Many people imagine they will provide replacement parts for damaged or injured organs.
Someday they might. But not soon.
Before paraplegics walk with regenerated spinal cords and diabetics get fresh-from-the-petri-dish pancreases, the stem cells will advance medicine in immediate ways.
They can:
— Show scientists what goes wrong with cancer cells and how to stop them.
— Replace animal models for diseases with human tissues grown in the lab.
— Cut years off drug development.
— Open research to more scientists because these stem cells do not involve human embryos.
"We're on the way now," said Dr. Michael Creer, director of laboratory medicine at St. Louis University and former director of the St. Louis Cord Blood Bank. "The opportunities are expanding enormously. What we think might work today could well change in the next few months … We still don't fully understand or appreciate what is possible."
When researchers in Wisconsin and Japan announced last month that they had independently engineered skin cells to behave like embryonic stem cells, the achievement seemed to be the pinnacle of stem cell science. Until then, human embryonic stem cells could be produced only by destroying embryos.
But no one knows how long it might be before stem cells can be used to replace or repair organs.
"People have to understand that we're not 'there' yet," said Dr. Steve Teitelbaum, a Washington University pathologist.
Jim Huettner, a cell biologist at Washington University, is one of the few people with firsthand knowledge of what human embryonic stem cells can and can't do. Huettner runs the only laboratory in St. Louis currently conducting research with human embryonic stem cells.
Researchers in his lab transform the stem cells into nerve cells to learn more about how nerves develop and which conditions lead a cell to become a certain kind of nerve — for example, one that will make muscles contract or the variety that gathers light, such as those in the retina. The research lays the foundation for the day when doctors might create nerves from stem cells to help patients walk or see again.
The new technique that can convert human skin cells into stem cells means that Huettner isn't likely to be alone in working with human stem cells for long.
Teitelbaum studies bone diseases in his laboratory. He and his colleagues have coaxed embryonic stem cells from mice to make a type of cell that breaks down bones. They plan to use the mouse cells to mimic human bone diseases. But the mouse cells are still only a model.
Teitelbaum is excited about the prospect of being able to take skin biopsies from children with crippling inherited bone diseases, make stem cells from their skin and then create bone-remodeling cells in the lab. Armed with those tools, Teitelbaum and his colleagues should be able to figure out exactly how the bone-building process goes awry in each patient. The cells also could be used to screen for drugs that will control bone-making.
Alzheimer's disease, and many other diseases also could be modeled in the lab and used for drug screening, Teitelbaum said. What isn't likely to happen soon is for stem cells to be grown into replacement parts, he said.
Adult stem cells in the form of bone marrow transplants, including umbilical cord blood transplants, have been used clinically for decades. Some other types of adult stem cell therapies are now in clinical trial, but results have been mixed and none are used routinely yet.
While the pace at which stem cell science is progressing may seem like a crawl, Huettner says the research has been speedy. After all, it took decades of trial and error to get bone marrow transplants to work and decades after that before they became routine, he said.
Human embryonic stem cells were first isolated in 1998.
"It's not unreasonable that it's taking this amount of time," Huettner said.
Existing embryonic stem cells probably won't be used in people because they are contaminated with animal sugars that would cause the human immune system to reject them. President George W. Bush's 2001 executive order bars federally funded researchers from working with newly developed stem cells that are harvested from embryos.
The new technique bypasses the need to create an embryo so it doesn't fall under Bush's ban, but cells made this way probably won't make it to the clinic anytime soon either.
That's because they are created by inserting four genes into the skin cell's DNA using a retrovirus. Sometimes those insertions can disrupt healthy genes and turn a cell cancerous. Most scientists agree that researchers will need to learn to reprogram the cells without using the viruses before they will be used in any sort of treatment.
Stem cells themselves have the power to become any type of cell in the body. If they are injected into the body, they will do just that, forming a benign tumor called a teratoma — a jumble of hair, teeth, skin, bone and other types of tissue. That's one of the ways the two groups tested whether their reprogrammed skin cells really were stem cells.
To avoid tumors from stem cells run amok, doctors must be sure that all of the cells they intend to transplant into a patient have converted into mature cells of the type that interests them — a spinal cord neuron, for instance. Now, about 90 percent of the stem cells in Huettner's petri dishes can be coaxed into becoming a nerve cell of some variety, he said. Scientists are learning to purify raw stem cells from the mature cells they want with mouse cells, but will need to repeat the work with human cells, Huettner said.
Even with pristine cultures of nerves or other replacement cells, the challenges of healing disease are enormous. While stem cells have been touted as a possible cure for Alzheimer's disease or spinal cord injuries, it's unlikely that a new neuron could wire into the brain or spinal cord in exactly the same way the damaged cell did, Creer said.
"The current idea that you can just throw a stem cell in and it will develop the way we want it to and find a happy place to live is a little bit naïve," Creer said.
But stem cell technology could help researchers learn to how to coax the brain to repair itself. And replacement brain cells and spinal cord cells can form entirely new connections. That means a person would need to learn to walk again the way a baby does and would have to relearn things Alzheimer's disease robbed from their memory.
With new stem cells in hand, the sky is the limit in terms of the medical accomplishments researchers can hope to make.
"Every time we think of an obstacle, we can think of an equally imaginative solution," Creer said.
Others recognize the hurdles too but share his optimism.
"There are challenges that will take a reasonable period of time to overcome," Teitelbaum said. "The yield is phenomenal if we can get this to work."
tsaey@post-dispatch.com | 314-340-8325
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