Mon, Apr. 01, 2002
By Lisa M. Krieger
Are they the light at the beginning of the tunnel? Or just a flash in the pan?
Since their discovery 20 years ago, stem cells have become one of medicine's great hopes, and one of science's greatest political and ethical dilemmas. But often lost underneath the arguments over the promise and peril of stem cell research are nuances that don't fit with all the drama. Despite a growing body of research, no one is sure whether these cells, once taken out of the lab and turned into medical treatments, will match expectations.
``The challenge now will be to find out just how well these cells can perform new tricks in their new homes,'' wrote Mark Sussman, a molecular biologist at the Children's Hospital and Research Foundation in Cincinnati, in a commentary in the journal Nature.
Stem cells, in their ability to morph into hundreds of different body tissues, have challenged a central truism of medicine: Organs can't regenerate themselves. A growing body of research supports the tantalizing potential of these cells to create tissue and build organs. Recent studies have found the ability for the cells to form everything from new blood vessels to brain tissue.
``It is the broadest window of research you can imagine,'' said Stanford University School of Medicine's Dr. Irving L. Weissman, who served as chairman of a National Academy of Sciences panel on stem cell and cloning research. But the complexity of the task cautions against the hope becoming grand promises -- and suggests that we are still years away from delivering cell-based therapies to the patient's bedside. And there remains debate about whether the federal government should pay for research using stem cells that come from human embryos.
``We have an obligation to go slow when people are concerned about ethical implications,'' said stem cell biologist Arthur Lander, chairman of the Department of Developmental and Cell Biology at the University of California-Irvine.
Regeneration of tissues damaged by disease is not a new notion, although it has been poorly understood. In the 1700s, Italian biologist Lazzaro Spallanzani asked: ``If frogs are able to renew their legs when young, why should they not do the same when further advanced?''
Salamanders, crabs and some other creatures can grow new appendages to replace lost ones. A hydra, when chopped into pieces, becomes a multitude of hydra. But all humans can renew with any great success on their own are hair, nails, skin and sometimes liver cells.
The promise of stem cell research is that someday humans could do more. All 75 trillion cells in the human body originate from stem cells -- unspecialized master cells that mature into specialized cells, or renew cells that die or become damaged. If these cells could be harnessed in the lab, perhaps they could be employed to help repair the body by renewing damaged tissues in severe disease and injury.
Kinds of stem cells
• Embryonic stem cells
These are found in very early human zygotes only a few days old. They are special because they are not committed to any specific function -- over time, they develop from a primordial state into any one of the 210 types of tissue that make up the body. The cells are as controversial as they are interesting, because human embryos must be destroyed to harvest them.
• Adult stem cells
These are found in mature tissue. As specialists, it is their job to renew and replace the cells in tissue. For instance, liver stem cells make liver cells; muscle stem cells make muscle. Their fate is determined by the signals they receive from their surroundings in the body. This limits their versatility. On the other hand, they have the benefit of being relatively abundant -- and much less controversial, as they can be obtained from many types of adult tissue.
Since the discovery of these two cell types, the field has acquired a gold rush mentality, with a great political and scientific debate over which cells -- embryonic or adult -- are superior. Because of their versatility, many scientists favor the potential of embryonic stem cells. But those who are opposed to embryo-based research argue that adult stem cells are not only as effective but also pose fewer ethical problems.
Could the political debate be sidestepped by forcing adult stem cells to switch their course so that brain cells, for instance, become blood cells instead? The jury is still out. Several studies have reported that they can. But in March, two research teams raised serious scientific doubts about claims that adult stem cells taken from one type of tissue can be converted into an entirely different type.
There has been great progress with embryonic stem cells. The Menlo Park-based biotech company Geron nabbed the early lead in exploiting these cells, because it financed pioneering research. But its progress is hard to assess since it is not obliged to publish research results.
What's been created
with embryonic stem cells In recent months, various university teams have announced startling progress in using embryonic stem cells to create:
• Blood vessels
Last week, Dr. Robert Langer and his team at the Massachusetts Institute of Technology reported that human embryonic stem cells have been nurtured to the point where they organized into blood vessels that could nourish the body. This could someday help repair damaged arteries and ailing hearts.
In the lab, they formed primitive vascular structures. When injected into rodents, the cells developed into tiny capillaries, small blood vessels.
• Blood-forming cells
University of Wisconsin scientists have coaxed human embryonic stem cells to become primitive types of blood cells that later develop into more mature types of blood cells. This research may prove important to blood banks because it could offer a way of growing an inexhaustible supply of red blood cells and platelets free of infectious agents.
• Brain cells
By tinkering with the cells in mice, a group led by Dr. Ronald D.G. McKay of the National Institutes of Health found the ingredients necessary to efficiently produce massive numbers of particular types of brain cells. These neurons are dedicated to the production of the neurotransmitter serotonin, which could help those with psychiatric disorders and ease symptoms of Parkinson's disease.
• Pancreatic cells
Pancreatic islets are the source of insulin, the hormone that alerts cells to take up glucose from the blood and helps regulate blood sugar. In mice, McKay and Dr. Nadya Lumelsky of the NIH identified a five-step method for making embryonic cells assemble into hormone-producing clusters like the islets of the pancreas gland.
McKay's study is the first to succeed in doing this, underlining how stem cells could be used to treat diabetes, a disease in which islet cells are destroyed.
• Spinal tissue
Dr. Hans Keirstead, a neurobiologist at UC's Reeve-Irvine Research Center, has implanted embryonic stem cells into a paralyzed rat. While the results are unpublished, video footage presented at a recent hearing at Stanford University showed the treated rat walking on all four feet around a child's plastic swimming pool. Keirstead believes that the stem cells can cause injured nerve cells to grow and conduct electricity across an injured section of spinal cord. If that occurs, the electrical impulses will resume flowing, possibly leading to the restoration of movement.
What's been created
with adult stem cells While embryonic stem cells have captured most of the publicity, adult stem cells have so far attracted far more investment. So far, more than a dozen types of adult stem cells have been identified, according to the National Institutes of Health. Biotech companies such as Layton BioScience of Atherton and StemCells of Sunnyvale are working to isolate these cells and grow them in large quantities. In the past year, academic scientists have announced the creation of:
• Blood vessels
Scientists at Columbia University in New York have identified cells in the adult bone marrow of rats that give rise to blood vessels. They then used these cells to create vessels around damaged areas in rats' hearts.
• Heart muscle cells
Dr. Donald Orlic of the National Institutes of Health and Dr. Piero Anversa of New York Medical College in Valhalla found that bone marrow cells injected into the damaged hearts of mice can develop into heart muscle cells and the cells that build blood vessels. These cells not only integrated into the stricken heart but also improved its function.
The discovery could help scientists eventually devise treatments to fix bad hearts.
``The promise is so enormous, it can't be passed up,'' said Hank Greely, professor of law and co-director of the Stanford University's Program in Genomics, Ethics and Society.
But these findings in both embryonic and adult stem cells raise the question: Since the body is so good at creating new cells, why doesn't it just fix itself?
No one knows for sure. That uncertainty is part of the reason promising lab results may not yield medical treatments soon.
One troubling explanation is that stem cells, no matter how intriguing, cannot change the course of underlying disease. It is conceivable that whatever causes an illness will claim these new cells, as well.
Other hurdles are yet to be overcome. Scientists still need to learn how cells make their choices to become a specific organ or piece of tissue. They worry that tissue regeneration is regulated by highly specialized biochemical cellular processes that may be tough to duplicate in the lab. Finally, once in the body, implanted cells may not match a patient's immune system -- and after all that hard work, be rejected.
It may take at least five to 10 years to move achievements from petri dishes and rodents into humans, say experts. After that, there could be further delays while the research undergoes review by federal regulatory officials. The history of medical science is littered with unexpected results, and the field of stem cell research is still in its infancy.
But what if...?
Perhaps, say experts. But the greatest danger, they say, is to not even try.
These early studies, no matter how exciting they look, must sooner or later prove themselves to science's most unforgiving jury -- the sick and the dying. And that day, scientists caution, is a long way off.
``It is not such a bad thing to go slow. We can cope with that. We are
going to make mistakes and jump to conclusions. We need to know a little
more about how ignorant we are,'' said stem cell biologist Lander of UC-Irvine.
Copyright, 2002, The Mercury News