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Malfunctioning bone marrow cells sabotage nerve cells in diabetes

August 23, 2005

Malfunctioning bone marrow cells that produce insulin appear to cause a dangerous nerve condition called neuropathy that disables many people with diabetes, said a research team led by Baylor College of Medicine in Houston.

The report from researchers at BCM, Shiga University of Medical Science in Japan, and the University of Chicago appears online today in the Proceedings of the National Academy of Sciences.

The finding not only provides a basis for understanding the dangerous nerve condition in diabetics, but could eventually lead to a treatment for this problem, said Dr. Lawrence Chan, chief of diabetes, endocrinology and metabolism at BCM. It may even provide an explanation for some of the other complications associated with the disease.

"These insulin-producing bone marrow cells are like terrorists that infiltrate the nerve-cell populations," he said. They produce proteins that can kill or subvert the purposes of nerve cells "almost like a suicide bomb," said Chan.

Diabetes mellitus, which afflicts roughly 18 million Americans, is a major health problem that affects multiple organs and tissues. Diabetes can be treated. However, treatment does not ward off many of the complications. Neuropathy is a common complication that causes pain and ultimately loss of sensation in the extremities and can lead to amputation.

Previously, Chan and members of his laboratory had found that bone marrow cells were among a group of cells in organs other than the pancreas that unexpectedly produced small amounts of insulin. In pursuing that finding, he and his colleagues found that the bone marrow cells that produced insulin adversely affected nerve cells or neurons.

"In our latest studies, we were surprised to discover that insulin-producing cells originating from bone marrow caused premature cell death and dysfunction when they merged with neurons, resulting in neuropathy," said Chan.

"It all began several years ago, when we were developing gene therapy to cure diabetes in mice. By chance, we observed insulin-producing bone marrow cells outside the pancreas, and wondered why these cells were migrating to other organs and whether they were detrimental or beneficial," said Chan.

In pursuit of this curious phenomenon, Drs. Tomoya Terashima and Hideto Kojima from BCM and Dr. Mineko Fujimiya of Shiga University of Medical Science in Shiga, Japan, in collaboration with Chan, performed numerous experiments in diabetic rats and mice. Their work defined the role of the aberrant cells in causing neuropathy.

They found that, in diabetes, only nerve cells that have fused with bone marrow cells display the abnormal function and premature death found in neuropathy. Nerve cells that have not merged with the insulin-producing bone marrow cells remain intact and function normally.

"Based on these findings, we speculate that a similar process contributes to some, if not all, of the other chronic complications of diabetes, and we look forward to pursuing this possibility. Discovering an underlying cause of diabetic neuropathy may enable us to design treatment strategies to prevent this complication in the future," concluded Chan.

Baylor College of Medicine