- The Washington Times - Friday, August 10, 2001

President Bush's decision to allow federal funding of some stem-cell research came as scientists were chafing to use the cells as tools for remaking medicine. But their challenge is huge.
Even though scientists have known of the existence of stem cells for many years and have studied them extensively in mice, it has been just three years since the discovery of human "pluripotent stem cells."
It was in November 1998 that John Gearhart at Baltimore's Johns Hopkins Hospital and James A. Thomson — working separately at the University of Wisconsin at Madison — isolated within human embryos primordial human cells that can develop into any part of the human body a finger, foot, heart, pancreas or entire individual.
Since that gigantic discovery, stem-cell research has raced ahead, accompanied not only by political and ethical debate but by a rash of heady reports of new breakthroughs. Yet, as Harvard University biochemist Evan Snyder says, stem-cell research is itself in an embryonic stage.
"All we're doing now is raising questions. Every [scientific] paper provides more questions. There are stem-cell therapies we can now apply, but there are no definitive answers. We need years of uninhibited, intense vigorous research to get answers."
The recent public debate about stem cells has involved three types: embryonic stem cells, adult stem cells, and hematopoietic stem cells, meaning a kind of adult cell found in bone marrow and blood and loosely called "blood stem cells."
"But where debate hits ground is on adult stem cells versus embryonic. Almost everything we know about stem cells comes from work in animals. From mice. We also know a little bit from research in primates," says Larry Goldstein, a biochemist at the University of California at San Diego.
What is certain is that human embryonic stem cells develop after an egg is fertilized or induced by cloning to grow into a blastocyst. That occurs roughly four days after fertilization. The microscopic cells cluster on the ring-like membrane of the emerging embryo.
But even before that stage and shortly after fertilization, a single stem cell forms. That cell is "totipotent," meaning it has total potential for development. The stem cells in the blastocyst are "pluripotent." They can develop into all human tissue except placenta.
Scientists can "harvest" the stem cells from the blastocyst and place them in special nutrients where they will multiply indefinitely.
Sixty such "stem-cell lines" already exist in academic and commercial laboratories across the country and experimentation using those lines will be eligible for federal funds under Mr. Bush's proposal.
If left in the blastocyst during normal embryonic development in the womb, the stem cells would begin to differentiate, becoming the tissue of toes, brain, and the rest of the body. But scientists are not yet sure how to make the cells living in a petri dish change into the kind of tissue they would like the cells to become.
Some recent tantalizing discoveries lead researchers to believe they will learn to do that. When scientists can make cells differentiate at will, the cells might be used to replace damaged tissue in, say, the brain or spine. If that could be done, doctors may become able to halt or cure Alzheimer's disease and enable paralyzed persons to walk.
Adult stem cells are found in the developed bodies of children and grown-ups. They have been discovered in bone marrow and blood.
Additionally, adult stem cells have been isolated in the eye, brain, muscle, liver, skin and elsewhere. They can multiply within the organs in which they originate.
The National Institutes of Health report that adult stem cells have been studied extensively and they have been used therapeutically for various diseases.
But, states one NIH study: "At this point, there is no isolated population of adult stem cells that is capable of forming all the kinds of cells of the body."
The report adds: "Adult stem cells are rare. Often they are difficult to identify, isolate and purify." Also, they do not reproduce themselves indefinitely in culture.
Week after week, however, there are reports of advances in adult stem-cell research. But most scientists say it's too early to tell whether any are breakthroughs.
"We're trying to learn which tissues really have [adult stem cells], which don't and what capacity the cells have to grow and differentiate," Mr. Goldstein said. "Some of the recent studies have been retracted, and some are not reproducible. So aside from bone marrow transplants, we don't really know the potential of the adult cells."
Adult stem cells are being extracted from umbilical cord blood, and there are media accounts of dramatic uses for such cells.
NIH researchers agree that umbilical cord blood provides "an abundant source" of blood stem cells. But "there do not appear to be any qualitative differences between the stem cells obtained from umbilical cord blood and those obtained from bone marrow or peripheral blood."



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