A Complication in Stem Cell Diabetes Research

Cells may not be producing insulin, Harvard researchers say

THURSDAY, Jan. 16, 2003 (HealthDayNews) -- Early reports that embryonic stem cells were transformed into insulin-producing beta cells -- a major goal in the search for a diabetes cure -- may have been too optimistic, scientists now report.

The insulin found in laboratory cultures may not have been produced by those cells, says a report in tomorrow's issue of Science. Instead, the cells may have been releasing insulin they absorbed from the medium on which they are grown.

Insulin is commonly used to promote the growth of cells in culture, says Dr. Jayaraj Rajagopal, a postdoctoral fellow at Harvard University and the Howard Hughes Medical Institute. "What we have shown is that when cells are cultured in the conditions previously reported, they have the ability to absorb insulin from the medium rather than making it themselves." They can then release the absorbed insulin for as long as two weeks, the scientists found.

When Rajagopal's group grew supposedly transformed stem cells in an insulin-free medium, no insulin was detected, he says.

The finding doesn't end the hope of using embryonic stem cells to make insulin-producing beta cells, which can then be implanted in diabetes patients, Rajagopal says. "What is needed is either modification of existing protocols [methods] or development of new protocols that will generate beta cells," he says. "What we are reporting is something scientists need to be aware of."

Dr. Linda B. Lester, an assistant professor of medicine at Oregon Health Sciences University and leader of a group working on the subject, is aware of the issue. Early reports of the Harvard work have been circulating among workers in the field, she says. Her group has reported successful transformation and "I still would stand behind the results," she says.

To Lester, a large part of the issue is that "we need other ways to identify a beta cell in culture" than the method used by Rajagopal and his colleagues.They used a chemical that stains all cells that carry insulin. The results can be confusing because it is not clear whether the insulin is produced by the cells or was absorbed from the medium on which they were grown, Lester says.

Her group has been using a different chemical that stains C-peptide, a byproduct that is made only when a cell is producing insulin. That method shows that at least some of the insulin in the cell culture was produced by the cells, she says.

The Oregon group has been working with embryonic stem cells of rhesus macaque monkeys, which avoids the major controversy about use of human embryo stem cells in medical research. The federal government has placed severe restrictions on research with human embryo stem cells.

Dr. Joel F. Habener, a professor of medicine at Harvard Medical School, is working on a technique that would make such concerns unnecessary. He's using adult human stem cells from the Isles of Langerhans, the insulin-secreting bodies in the pancreas. Transplants of islet cells have worked well in humans, but the problem is a lack of donors, Habener says--"only enough for one in every 500 people who need it."

His idea is to take adult pancreatic stem cells -- in the best case from people who will need them -- then grow them in culture and implant them in diabetics. The technique has worked well in mice, Habener says.

And he stopped using the insulin-rich growth medium most laboratories use a while ago because its contaminating effects became clear, he adds.

More information

You can learn more about stem cell research from the Joslin Diabetes Center or from the National Institutes of Health.

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