Scientists have found a small compound that could direct stem cells to become insulin-secreting pancreatic beta cells. The strategy, published online in Nature Chemical Biology, holds great promise for transplantation therapy of metabolic diseases such as diabetes.
In the development of organs in human embryos, the pancreas progenitors develop from endoderm cells, which themselves had been derived from human embryonic stem cells (hESCs). Since it is not known what cells along the pathway will be needed for transplantation therapy, a major goal among researchers is to generate large numbers of fully mature insulin-secreting pancreatic cells, the beta cells.
The research groups of Douglas Melton and Stuart Schreiber performed a high-content screen to identify a compound, ILV, that when added to definitive endoderm derived from hESCs, generated large numbers of cells that express Pdx1 and other pancreatic markers. Implantation of the cells into mice kidney capsules further generated a population of insulin-positive cells in vivo, suggesting that they are on a key pathway towards formation of insulin-secreting beta cells.
Based on ILV's mechanism of action, the results show that targeting the protein kinase C pathway could lead to improvements in the numbers of beta cells that can be formed.
Douglas Melton (Harvard University, Cambridge, MA, USA)
Abstract available online.
(C) Nature Chemical Biology press release.
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