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Scientists use transplanted stem cells to reverse juvenile diabetes in mice

All year cell biologists have been aquiver with anticipation. Since the isolation of embryonic stem cells a little more than a year ago, labs all over the world have been exploring the possibility of using stem cells to restore damaged or lost tissue. Exciting results are now starting to come in.

What is a stem cell? At the dawn of a human life, a sperm fertilizes an egg to create a single cell destined to become a child. As development commences, that cell begins to divide, producing a small ball of a few dozen cells. At this very early point, each of these cells is identical. We call these cells embryonic stem cells. Each one of them is capable by itself of developing into a healthy individual. In cattle breeding, for example, these cells are frequently separated by the breeder and used to produce multiple clones of valuable offspring.

The medical value of these embryonic stem cells is that they can develop into any tissue. Last June in this column I described pathfinding experiments in which embryonic stem cells were used to restore lost brain tissue in mice. These very promising experiments suggest a possible treatment for spinal cord injury, and are being pursued aggressively. They are, however, quite controversial, as embryonic stem cells are typically isolated from tissue of discarded or aborted embryos, raising serious ethical issues.

New results promise a neat way around the ethical maze presented by stem cells derived from embryos. Go back for a moment to what we were saying about how a human child develops. What happens next to the embryonic stem cells? They start to take different developmental paths. Some become destined to form nerve tissue, and after this decision is taken cannot ever produce any other kind of cell. They are then called nerve stem cells. Others become specialized to produce blood, still others muscle. Each major tissue is represented by its own kind of tissue-specific stem cell. Now here's the key point: As development proceeds, these tissue-specific stem cells persist. Even in adults. So why not use these adult cells, rather than embryonic stem cells?

The approach seems very straight forward, and indeed blood stem cells are routinely used to replenish the bone marrow of cancer patients after marrow-destroying therapy. The problem with extending the approach is that it has not always been easy to find the tissue-specific stem cell you want. The very promising result reported last week by Dr. Ammon Peck and a team of researchers at the University of Florida in Gainesville concerns a particularly vexing problem, that of type-1 or juvenile diabetes.

A person with juvenile diabetes lacks insulin-producing pancreas cells, because their immune system has mistakenly turned against them and destroyed them. They are no longer able to produce enough insulin to control

their blood sugar levels and must take insulin daily. Adding back new insulin-producing cells called islet cells has been tried many times, but doesn't work well. Immune cells continue to destroy them.

Peck and his team reasoned, why not add instead the stem cells that produce islet cells? They would be able to produce a continuous supply of new islet cells, replacing those lost to immune attack. Because there would always be cells to make insulin, the diabetes would be cured.

No one knew just what such a stem cell looked like, but the researchers knew they come from the epithelial cells that line the pancreas ducts. Surely some must still lurk there unseen. So the research team took a bunch of these epithelial cells from mice and grew them in tissue culture until they had lots of them.

Were the stem cells they sought present in the cell culture they had prepared? Yes. In laboratory dishes the cell culture produced insulin in response to sugar, indicating islet cells had developed in the growing culture, islet cells that must have been produced from stem cells.

Now on to juvenile diabetes. The scientists injected their cell culture into the pancreas of mice specially bred to develop juvenile diabetes. Unable to manufacture their own insulin because they had no islet cells, these diabetic mice could not survive without daily insulin. What happened? The diabetes was reversed! The mice no longer required insulin.

Impatient to see in more detail what had happened, the researchers sacrificed the mice and examined the cells of their pancreas. The mice appear to have perfectly normal islet cells.

One might have wished the researchers waited a little longer before terminating the experiment. It is not clear whether the cure was transitory or long term. Still, there is no escaping the conclusion that injection of a culture of adult stem cells cured their juvenile diabetes.

While certainly encouraging, a mouse is not a human, and there is no guarantee the approach will work in humans. But there is every reason to believe it might. The experiment is being repeated now with humans. People suffering from juvenile diabetes are being treated with human pancreatic duct cells obtained from people who have died and donated their organs for research. No ethical issues arise from using cells of adult organ donors, and initial results look promising.

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