Role of Maternal Cells in Diabetes ProbedRole of Maternal Cells in Diabetes Probed

Some cells passed from mother to child during pregnancy can differentiate into pancreatic islet beta cells and may play a role in aiding the production of insulin in children with type 1 diabetes, according to a multinational team of researchers from the United States, France, and the United Kingdom (Nelson JL et al. Proc Natl Acad Sci U S A. doi:10.1073/pnas.0606169104 [published online ahead of print January 23, 2007]).

Previous research had documented that maternal cells are transmitted from mother to fetus and that they persist (Artlett CM et al. Lancet. 2000;356:2155-2156; Reed AM et al. Lancet. 2000;356:2156-2157). But the investigators who made the new discovery that the maternal cells differentiate into islet cells say the finding suggests that the maternal microchimeric cells in children with diabetes may play a beneficial role that might be exploited in future treatments for the disease.

While many questions remain about the precise activities of these cells and their potential contribution to the development of treatments, the findings add to those from other investigations that seek to understand the role played by cells transferred from mother to fetus and vice versa, both in normal biology and in disease. In previous work, scientists had linked cells transferred from fetus to mother to the development of some autoimmune diseases, such as scleroderma.

The research team led by J. Lee Nelson, MD, a clinical research professor at the Fred Hutchinson Cancer Research Center, in Seattle, used a panel of polymerase chain reaction assays to determine the quantities of maternal microchimeric cells in the blood of 172 individuals: 94 with type 1 diabetes, 54 of their unaffected siblings, and 24 unrelated healthy individuals. They found that 51% of the patients with diabetes had such cells, as did 33% of unaffected siblings and 17% of healthy controls. Of those who had maternal cells in their circulation, the patients with diabetes had the highest concentrations of these maternal cells, followed by their unaffected siblings; unrelated healthy individuals had the lowest concentration of maternal cells.

The researchers also examined cadaver pancreases of 4 males, including 1 with type 1 diabetes, to determine if any genetically female cells—presumably of maternal descent—were present and to identify what types of cells they were. Female hematopoietic cells were rare, but female islet cells comprised 0.39% to 0.96% of the total number of islet cells.

The data suggest that cells from a mother pass to their children in utero, persist, and can differentiate into islet cells. Nelson said the results also suggest that maternal cells might serve to aid the child's cells and help to regenerate damaged tissue, and that maternal cells do not appear to trigger an immune response that contributes to diabetes, as she had hypothesized prior to the study. In the article, she and her colleagues explain that few female cells were found in the autopsied pancreases, suggesting they are not themselves causing the autoimmune response. The maternal microchimeric cells are also unlikely to be targets for an autoimmune response because higher blood levels of maternal microchimeric cells were not observed in recently diagnosed patients.

However, microchimerism researcher Carol M. Artlett, PhD, an assistant professor of microbiology and immunology at Drexel University College of Medicine in Philadelphia, said it may be premature to conclude that the cells are not causing an autoimmune response or that they are facilitating repair of the pancreas tissue. “It's kind of hard to say what [the maternal cells] are doing,” Artlett said, noting that Nelson and colleagues did not determine how many of the child's own cells were working to repair the organ or whether the maternal cells are perhaps doing the exact same thing as the autologous cells.

It is not yet clear whether these maternally derived cells serve any special function, said Artlett, who for the past decade has been trying to characterize the function of maternal cells that are transferred to, and persist in, a woman's offspring. She explained that she and coworkers have found maternal cells in inflammatory lesions in scleroderma patients, and determined that the maternal cells express antigens similar to those of the autologous cells in the same lesion. She added that further studies characterizing the function of these maternal microchimeric cells are necessary.

Nelson noted that one of her colleagues, Kathleen M. Gillespie, PhD, of the University of Bristol in England, is currently working to isolate and better characterize the cells of maternal origin in pancreatic tissue and determine their spectrum of function.