Posted by Ellen on July 08, 2001 at 06:49:47:
Sunday, July 8, 2001
Stem cell central
By DIANE CHUN
Sun medical writer
They are basic scientists, pathologists, neuroscientists and blood specialists working in what is arguably the hottest research field in the country today - stem cell biology.
The debate over the appropriateness of their research rages in news magazines and on editorial pages, but these University of Florida researchers say there is nothing they'd rather be doing.
(Picture: Dennis Steindler, front, is one of a group of stem cell researchers at UF. Behind him, from left, are Byron Petersen, Paul Reier, Edward Scott, and Ammon "Bruff" Peck. ROB WITZEL/Special to The Sun )
They'll tell you the rules of cell biology are being rewritten right now. And in a field where the one constant is change, they want UF to be front and center - no matter how intense the controversy may get.
Stem cell research has electrified the scientific community, with potential application in Parkinson's disease, Alzheimer's disease, heart disease, stroke, diabetes and spinal injuries. But for those who believe life begins at conception, harvesting embryonic stem cells rather than stem cells from mature tissue is tantamount to murder.
As a group, UF's stem cell scientists want the public to see past the rhetoric to the ever-changing research. They see the adult stem cell, not fetal tissue, as the ultimate in what will lead to actual treatments for crippling diseases.
Stem cells are like blank slates. In the embryo, they have the potential to grow into any of the 220 cell types in the human body. Researchers believe the adult stem cells may be the only cells left in an adult that haven't been programmed to make a specific tissue type - a brain or a liver or blood. Can these older cells be pushed to make other things? Studies under way now may provide the answers.
"The beauty of stem cell biology, and regenerative biology in general, right now is that all the rules are up for grabs. And when you get together a bunch of investigators in a very unique environment where they can do the cross-talk, anywhere in the world could be the mecca of this new applied stem cell biology. Why not here?" said Dennis Steindler, professor of neuroscience and neurosurgery in UF's College of Medicine who also is affiliated with the McKnight Brain Institute and UF Cancer Center.
Steindler moved his entire research group from the University of Tennessee at Memphis in March to continue his research into the potential of a population of adult cells within the brain to repair injuries to the brain itself - self-healing, as it were.
He and his research colleagues have demonstrated that in tissue cultures they can multiply the numbers of brain stem cells culled from cadavers and patients undergoing surgery for epilepsy. That opened the door to ongoing efforts to generate enough tissue for transplant therapies.
The team also has reported that they had developed techniques to transform mature brain cells back into stem cells, using special growth factors in tissue cultures.
"Our goal is to develop neural stem cell techniques for repairing a damaged spinal cord or treating brain diseases such as Huntington's, Parkinson's and Alzheimer's, not through tissue transplants but by finding the growth factors that induce existing cells within one's own brain to begin making a lot of new cells," Steindler reported.
"In essence, wouldn't it be nice if you had a brain injury, to just take a pill to begin healing? I think we'll see that day."
No magic bullet
"In a simple sense, we are still trying to learn how to put a nervous system back together," said Paul Reier, who as Overstreet professor in the Brain Institute's department of neuroscience is studying the potential for spinal cord regeneration.
His work in collaboration with Douglas Anderson, also an Overstreet professor and chair of the department of neuroscience and neurological surgery, grabbed headlines in 1999 when they reported that embryonic cells could be transplanted into injured spinal cords to restore a limited ability to walk. In trials since, they have tried to determine whether the grafted tissue will survive and prevent further loss of function. The results so far look good.
Reier's work with embryonic tissue separates him from his colleagues working with adult stem cells. It also puts him closer to the hottest point of debate: Should embryonic stem cells - highly flexible cells with the potential to morph into any human tissue - be allowed in stem cell research?
"We know that there is no magic bullet to repairing the nervous system, no one single cure," Reier said. "However, the treatment of a variety of neurological disorders will probably gain from at least having one limb of the combined therapy being a cellular replacement strategy.
"Our work up to now has largely been related to fetal tissue, but the primary fetal tissue we are using in transplant work also represents the principal stem cell components, so we're learning something from that as a template.
"As we learn more from those cells experimentally, we're hoping that we can manufacture cells that can be used effectively in place of primary fetal tissue."
Avoiding limits
Byron Petersen, an assistant professor in the College of Medicine's department of pathology, immunology and laboratory medicine, is looking at adult stem cells derived from bone marrow and their potential to regenerate liver, a connection he has proved in a rat model.
Can these liver stem cells then be changed into a neural cell? A pancreatic cell? A blood cell?
"Even though the climate of stem cell research is very debatable and hotly argued, I think that all three aspects of stem cell research - embryonic, fetal and adult - should be pursued quite diligently until we figure out how to use the adult stem cell," Petersen said.
"Ultimately, I think that is going to be the way that we will eventually treat patients or cure patients. Not through embryonic or fetal stem cells, although they may play a part, but if you are suffering from liver failure, I would be able to take bone marrow stem cells from your body, grow them up and transplant them back into you to rescue your liver.
"It's called self-healing, and I think within the next 20 years, we'll see it."
Petersen added, "As Emerson once said, 'What limits us we call fate.' So if we put limits on what we do, we are not going to be able to pursue the ultimate possibilities."
'Local flavor'
In this group, Edward Scott would probably describe himself as "the blood man."
An associate professor and program director in molecular genetics and molecular biology in the College of Medicine, he works with hematopoietic stem cells in the bone marrow and the genes involved in getting them to differentiate into the various blood cell types.
"We've had people studying this for several decades," he said. "The same is not yet true for nervous system cells, pancreatic cells, liver cells. We're still in the 'What do these guys look like?' stage. We need to lay hands on them, play with them. It's like getting new toys. We need to figure out what they can do before trying to use them for therapy."
Scott is helping the cancer center put together a coordinated program in stem cell biology, taking full advantage of shared information between researchers and disciplines.
He sees nonblood cells as the focus of the next five years in the stem cell biology field, and he says his fellow researchers have the advantage of a pathway laid out by the work that went into figuring out the blood stem cell.
"We may eventually find that all these stem cells are highly related. We talk about the adult stem cell that lives in the liver or the brain, but it's like people who live in England and America. We have slightly different accents and do things a little bit differently, but we are still basically the same folks," Scott said.
"That's the same idea, that these stem cells may pick up some local flavor from their microenvironment."
Times have changed
If stem cell researchers are in the spotlight today, UF's representatives remember when the response of the scientific community to their findings was far less receptive.
Ammon B. "Bruff" Peck, professor in the College of Medicine's department of pathology, immunology and laboratory medicine, who has been here since 1979, remembers presenting a seminal paper in 1994.
"In the debate over the use of embryonic versus adult stem cells, we clearly showed that an adult stem cell was capable of differentiation. We took liver stem cells from an adolescent or adult and showed the cell population in vitro could differentiate into pancreatic islet cells (those that secrete hormones important in controlling sugar metabolism) and even recreate the islet structure itself."
Peck said when he presented the work at a meeting of the American Diabetes Association, he was escorted off the podium.
"We'd been working on transdifferentiation since 1993, but it was a terribly radical position in 1994," he said.
"I almost came to blows with my mentor over the concept of a bone marrow stem cell becoming liver. He went so far as to refuse to put his name on my paper," Petersen recalled. "But, hey, he gave me my career."
"It goes back to (the German philosopher) Nietzsche," Petersen said. "Many men fail as original thinkers, simply because their memory is too good."
This is one group of researchers who are not only thinking outside the box, they've discarded the box.
"That's the beauty of what we're doing. Every day there's something new coming out," Petersen said. "We are rewriting medicine right now."
Diane Chun can be reached at 374-5041 or at diane.chun@gainesvillesun.com.