L.J. Gonez,
A.M. Holland, G. Naselli, L.C. Harrison
Type 1 diabetes occurs when the immune system mistakenly attacks the beta cells in the pancreas. These beta cells produce the hormone insulin, which transfers glucose into the organs and tissues of the body where it is used for energy. To cure type 1 diabetes, we would therefore need to either replace or regenerate these beta cells, as well as preventing the immune system from attacking them again.
The beta-cell mass in the adult pancreas is capable of limited regeneration when the pancreas is injured, or when there is increased physiological demand, for example during pregnancy. In part, this regeneration may arise from progenitor cells in the pancreas - 'parent' or 'stem' cells which can produce new cells capable of growing into either beta cells or other pancreatic cells. Identifying these progenitor cells, and understanding the way in which they mature is an important step in finding new therapies for type 1 diabetes. However, although there have been many advances in our understanding of the way the pancreas grows and develops before birth, identification of progenitor cells in the adult pancreas remains elusive.
We have created a mouse model with which to study the adult pancreas. In these mice, a fluorescent protein has been put under the control of a pancreatic beta-cell transcription factor. This allows us to see where and when beta cells are being created. This mouse also contains a protein that 'immortalises' the cell populations we wish to study, so that by increasing progenitor cell numbers in the laboratory, we have a better opportunity to determine how to turn them into beta cells. We have used this mouse model to show that progenitor cells capable of becoming beta cells exist in the adult pancreas. These cells are associated with the pancreatic duct system, which normally carries enzymes secreted from the pancreas into the digestive system.
Furthermore, we have used experimental systems known to identify and isolate adult stem cells in other organs to purify progenitor cells from the adult pancreas. These cells can form pancreatic epithelial colonies when cultured in the laboratory. The creation of these colonies, which can be maintained and worked with in the lab, is important to our work, as progenitor cells are quite rare and short-lived in mice.
We are now working to define and characterise these cells to determine the conditions required to turn them into functional beta cells.
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