详细记录  
题名:Stable insulin-secreting ducts formed by reprogramming of cells in the liver using a three-gene cocktail and a PPAR agonist.
作者:BANGA A; GREDER LV; DUTTON JR; SLACK JM;
来源:Gene Ther. 2013 Oct 3. doi: 10.1038/gt.2013.50. [ IF= 0.00 ] ]
URL :10.1038/gt.2013.50
日期:20131104
摘要:With the long-term aim of developing a new type of therapy for diabetes, we have
investigated the reprogramming of liver cells in normal mice toward a pancreatic
phenotype using the gene combination Pdx1, Ngn3, MafA. CD1 mice were rendered
diabetic with streptozotocin and given a single dose of Ad-PNM, an adenoviral
vector containing all three genes. Ad-PNM induced hepatocytes of the liver to
produce insulin, and the blood glucose became normalized. But over several weeks,
the insulin-positive cells were lost and the blood glucose rose back to diabetic
levels. Simultaneous administration of a peroxisome-proliferator-activated
receptor agonist, WY14643, caused remission of diabetes at a lower dose of Ad-PNM
and also caused the appearance of a population of insulin-secreting ductal
structures in the liver. The insulin-positive ducts were stable and were able to
relieve diabetes in the long term. We show that the effect of WY14643 is
associated with the promotion of cell division of the ductal cells, which may
increase their susceptibility to being reprogrammed toward a beta cell fate.Gene
Therapy advance online publication, 3 October 2013; doi:10.1038/gt.2013.50.

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