Thursday, June 6, 2013
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Direct conversion of
fibroblasts to insulin-secreting cells using DNA demethylating agents
In vitro and mouse studies suggest demethylating agents
could be used to directly convert adult fibroblasts into insulin-producing
cells. Adult human skin fibroblasts were exposed first to the DNA
demethylating agent Vidaza
and then to a three-step pancreatic differentiation protocol to produce a
population containing about 35% pancreatic cells. In culture, the converted
pancreatic cells released insulin in response to glucose challenge. In mice
with chemically induced diabetes, injection of the converted pancreatic cells
into the spinal cord restored normal glucose levels and tolerance. Next steps
include developing a protocol to produce patient-specific pancreatic cells.
Inc. and Nippon
Shinyaku Co. Ltd. market the DNA
methyltransferase inhibitor Vidaza azacitidine to treat
myelodysplastic syndrome (MDS). Celgene and Pfizer also market the drug to
treat acute myelogenous leukemia (AML).
Published online June 6, 2013
Patent application filed;
available for licensing
Pennarossa, G. et al.
Proc. Natl. Acad. Sci. USA; published online
May 21, 2013;
Contact: Tiziana A.L. Brevini, University of Milan, Milan,
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