Tuesday, January 23, 2007

 

Cells passed from mother to child during pregnancy live on and make insulin

It has been known for some years that mother and baby exchange stem cells in the course of pregnancy, and that these may live on for many years [1], apparently tolerated by the new host. The phenomenon is known as microchimerism [2], and it is still unclear as to whether the presence of such cells can be harmful to the recipient.

A Bristol team has looked for maternal cells in children with type 1 diabetes, an immune-mediated disorder, and found that around 20 per cent of these children have unusually high levels of maternal DNA in their circulation. An even more surprising finding is that some maternal cells have entered the child's pancreas and are functioning there as insulin-producing beta cells.

The study, initially undertaken in the belief that maternal cells might trigger autoimmunity in the child, has now taken an interesting new twist, for the maternal cells might even be helping the child to repair injury.

In this study [3], published in the January 22 issue of the Proceedings of the National Academy of Sciences (PNAS), Dr Kathleen Gillespie and Professor Edwin Gale from the Department of Clinical Science at North Bristol in collaboration with Professor J. Lee Nelson and colleagues at Fred Hutchinson Cancer Research Center, Seattle, found no evidence that the mother's cells were attacking the child's insulin cells and no evidence that the maternal cells were targets of an immune response from the child's immune system.

Instead, the researchers found a small number of female islet beta cells in male pancreatic tissue (procured from autopsies) that produced insulin. Microchimerism is the term used when an individual harbors cells or DNA that originate from another genetically distinct individual. "To our knowledge a maternal contribution to endocrine function has not previously been described," the authors said. "Our findings also raise the possibility that naturally acquired microchimerism might be exploited to therapeutic benefit."

The study also found significantly higher levels of maternal DNA in the peripheral blood of 94 children and adults with Type 1 diabetes as compared to 54 unaffected siblings and 24 unrelated healthy subjects they studied.

Originally, the study of 172 individuals and pancreatic tissue from four males was designed to ask the question whether small numbers of maternal cells might be involved in any way in Type 1 diabetes. "Our initial theory was that perhaps, in some situations, too many cells cross from mother to fetus in pregnancy. Could diabetes result because the child lost tolerance to those cells because they are genetically half foreign? Our research appears to disprove this," said Professor Gale. "It is possible that the maternal cells may even be helping to regenerate damaged tissue in the pancreas."

The investigators are excited about the observation that maternal microchimerism results in cells that make insulin - these maternal stem cells could provide new insights into how insulin producing beta cells are generated. [Source: University of Bristol]

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[1] Fetal microchimerism - what our children leave behind
Michael Verneris
Blood 2003 102: 3465-3466.

"Fetal microchimerism (FMc) describes the persistence of low numbers of fetal cells in the mother after a pregnancy. A number of recent studies suggests FMc may play a role in the etiology of some autoimmune diseases. Remarkably, FMc has been demonstrated to persist for up to 38 years after pregnancy and has been found in multiple lymphocyte subsets and in early lymphoid precursors. In a single patient, FMc was demonstrated in CD34+ cells, suggesting that FMc may result from the engraftment of a long-term repopulating or stem cell."

[2] Definition from MedicineNet's Medical Dictionary:

Microchimerism: The presence of two genetically distinct and separately derived populations of cells, one population being at a low concentration, in the same individual or an organ such as the bone marrow. Microchimerism may be due to transfer of cells between mother and fetus or between two twins. Other sources of microchimerism include blood transfusions and transplants. See also: Chimera.

[3] Lee Nelson, Kathleen M. Gillespie, Nathalie C. Lambert, Anne M. Stevens, Laurence S. Loubiere, Joe C. Rutledge, Wendy M. Leisenring, Timothy D. Erickson, Zhen Yan, Meghan E. Mullarkey, Nick D. Boespflug, Polly J. Bingley, and Edwin A. M. Gale
Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet {beta} cell microchimerism
PNAS published January 23, 2007, 10.1073/pnas.0606169104

Maternal cells have recently been found in the circulation and tissues of mothers' immune-competent children, including in adult life, and is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes (T1D) is an autoimmune disease that primarily affects children and young adults.

To identify and quantify MMc, we developed a panel of quantitative PCR assays targeting nontransmitted, nonshared maternal-specific HLA alleles. MMc was assayed in peripheral blood from 172 individuals, 94 with T1D, 54 unaffected siblings, and 24 unrelated healthy subjects. MMc levels, expressed as the genome equivalent per 100,000 proband cells, were significantly higher in T1D patients than unaffected siblings and healthy subjects. Medians and ranges, respectively, were 0.09 (0-530), 0 (0-153), and 0 (0-7.9). Differences between groups were evident irrespective of HLA genotypes. However, for patients with the T1D-associated DQB1*0302-DRB1*04 haplotype, MMc was found more often when the haplotype was paternally (70%) rather than maternally transmitted (14%).

In other studies, we looked for female islet {beta} cells in four male pancreases from autopsies, one from a T1D patient, employing FISH for X and Y chromosomes with concomitant CD45 and {beta} cell insulin staining. Female islet {beta} cells (presumed maternal) formed 0.39-0.96% of the total, whereas female hematopoietic cells were very rare. Thus, T1D patients have higher levels of MMc in their circulation than unaffected siblings and healthy individuals, and MMc contributes to islet {beta} cells in a mother's progeny.

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A recent post:

"Scientists create 3-D scaffold for growing stem cells"

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