Report cites embryonic cells in possible cure for diabetes

By Robert Cooke
Newsday

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The researchers also found some evidence that insulin-making beta cells can renew themselves without new stem cells. This could someday offer a way to treat diabetes by replacing cells killed by an errant immune system, assuming some beta cells survive.

About 18 million Americans have diabetes, and between 5 percent and 10 percent of them have Type I, the more severe insulin-dependent form of the metabolic disease. In Type I diabetes, the insulin-making beta cells are gradually destroyed, killed off by the patient's own immune system. Once they're gone, regular injections of insulin, which regulates blood sugar, are required. Type I diabetes was the form studied by the Harvard team.

The discoveries, announced last week in the journal Nature, help answer long-simmering debates in biomedicine. The most contentious is whether adult stem cells wait in the pancreas, ready to divide and supply more beta cells if needed, or whether doctors must add new beta cells derived from stem cells harvested from embryos. Embryonic stem cells can divide and turn into every type of tissue. Adult stem cells are thought to be able to make only a particular type of tissue.

The new research determined that adult stem cells aren't found in the pancreas; that embryonic stem cells may provide a source of new, implantable beta cells; and that there's a remote chance that a small residue of beta cells in a patient's pancreas may be expandable enough to be useful.

According to biologist Douglas Melton and his colleagues, "how tissues generate and maintain the correct number of cells is a fundamental problem in biology." And in principle, there are two ways to maintain the proper balance. First, cells already in tissue may divide and replace cells that have died. Or, second, new and inexperienced stem cells may migrate in, or be implanted, to replace missing cells. Either way, the goal is to keep an important function going.

These ideas are vigorously debated, in part, because of ethical concerns. Many people, including some scientists, object to destroying human embryos to harvest stem cells. Others argue that it's unethical not to use stem cells to treat diseases, especially since fertility clinics dispose of surplus embryos. The stem-cell issue is also rooted in arguments over abortion.

Dr. George Daley, who is involved in stem-cell research at Children's Hospital in Boston, said the new report "is a fabulous paper. It is an extremely critical experiment because it highlights the lack of an adult stem-cell population for the pancreas. It makes the argument that if we ever hope to replace pancreatic beta cells, we can't hope to find them in the pancreas of cadavers, or from donors. We'll have to return to the embryo to find the source of these cells."

In their tests in mice, the Harvard research team, led by Melton, saw no signs that adult stem cells wait in the pancreas, or that adult stem cells might wander in from bone marrow or other tissue. Instead, the only new beta cells they could find came from older beta cells via normal cell division. After adulthood, it was unlikely new beta cells would appear.

Nonetheless, Melton added, the most interesting question has been "what happens in mature pancreatic tissue to both maintain the pancreas and regenerate it? Previous studies have suggested that there are sources of adult stem cells that might give rise to beta cells" that produce insulin as needed.

But the earlier studies were inconclusive. Melton and colleagues created a gene-based identification system that shows the source of each new beta cell.

Their tests made it clear that none of the mouse beta cells had come from stem cells. The new cells were the offspring of mature beta cells, meaning that an existing tissue was rebuilding itself.

This might lead to a treatment for diabetes, Melton said, if it turns out that patients with insulin-dependent diabetes have beta cells remaining. If so, these might somehow be stimulated to grow. But, he said, if all the original beta cells are gone, erased by the immune system, it means any replacement cells must come from embryonic stem cells and be implanted into the pancreas.

Copyright © 2004 The Seattle Times Company

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