Sperm May Hold Cure for Diabetes

New therapy? Researchers have used cells that develop into sperm
to create a type of pancreatic cell (blue) that secrete insulin (red),
which may one day cure type 1 diabetes in men.

Men with type 1 diabetes may one day be able to use the stem cells that become sperm to replace their insulin-producing pancreatic cells. Such transplants would eliminate the need for frequent daily insulin injections to control blood sugar.

Type 1 diabetes occurs when the immune system attacks and destroys insulin-producing islet cells in the pancreas. Without insulin to help cells absorb blood glucose, a person can't use energy from food. Untreated type 1 diabetes is always fatal, but regular insulin injections and blood-sugar monitoring can allow patients to have fairly normal lives.

Occasionally, insulin injections aren't enough to keep type 1 diabetes in check, however. So in the late 1990s, researchers at the University of Alberta in Canada began transplanting islet cells from cadavers into diabetics. This isn't an ideal solution, though, as recipients have to remain on immune-suppressing medication for the rest of their lives to prevent transplant rejection and usually still require some insulin injections.

Stem cell biologist G. Ian Gallicano of Georgetown University in Washington, D.C., and colleagues believe they have found a method that would give diabetics the advantages of islet cell transplantation without the need for immunosuppressant drugs. Millions of sperm cells are created each day from stem cells in the testes known as spermatogonial stem cells (SSCs). The researchers harvested SSCs from human testicular tissue and engineered them to become pluripotent stem cells, which have the capability to specialize into any type of cell, a process that took 2 weeks. Then, the researchers prodded these stem cells to develop into islet cells.

As they reported here yesterday at the annual meeting of the American Society for Cell Biology, Gallicano and colleagues transplanted the engineered human islet cells into diabetic mice that don't have an immune system and so can't attack the inserted cells. The transplants lowered the mice's high blood glucose levels, a good sign that the cells would do the same thing in humans.

Gallicano cautions, however, that the technique isn't ready for people just yet. "We don't get enough insulin from each cell to cure diabetes in humans."

That's a concern echoed by Sheng Ding, a biochemist at The Scripps Research Institute in San Diego, California, who wasn't involved in the research. Before the technique is ready for the clinic, he says, researchers will need to increase insulin production in the transplanted cells. Still, Ding says, "This represents one direction to pursue for ultimately curing type 1 diabetes."

This isn't the first attempt to treat or cure diabetes with stem cells. Researchers had previously used cells from skin or other tissues to create a slightly different type of stem cell, known as an induced pluripotent stem (iPS) cell, which could then go on to replace the damaged islet cells. Using iPS cells does have some advantages, Gallicano says. They don't require an invasive procedure to obtain, and they work for both sexes. However, researchers need to add four genes to morph cells into iPS cells. The genes don't always insert in the right place, which could cause cancer or cell death, he says.

The human SSCs, though, found in men only, are already stem cells and don't need those four genes turned on. "We don't have to do anything to make them pluripotent except take them out of their niche" in the testes, Gallicano says.

The researchers hope that they can find a method that would benefit female diabetics as well. Gallicano says he sees no reason why egg precursor stem cells can't also be used. One major difference is that the egg stem cells have only one copy of every gene, whereas the SSCs have two copies, like other cells in the body, which makes it easier to apply the technique to SSCs.

There's one more hurdle, says Gallicano, which is finding out whether the immune system, which has already created antibodies against the body's islet cells, will attack the transplanted cells as well.