Long-term diabetes reversal with genetic switch

Two US researchers who five years ago cured diabetic mice with gene therapy have found out how it happens: adult stem cells.

Dr Lawrence Chan and Dr Vijay Yechoor of the Baylor College of Medicine in Texas transferred the transcription factor Neurogenin3 (Ngn3) into the livers of diabetic mice and saw long-term reversal of their diabetes.

Now they have found out how: Ngn3 induces a short-term increase in insulin production, but also a long-term induction of islet-like cell clusters that appear to arise from hepatic progenitor cells.

The progenitor cells are thought to hibernate near the portal vein until they are needed to make mature liver or bile duct cells. Ngn3, however, encourages them down the islet lineage instead.

This, the researchers write, is called transdetermination: the progenitor cells are lineage-determined but not terminally differentiated. The added gene can switch their lineage from hepatic to islet.

While these are early days, the researchers say the concept is important because it shows normal adult stem cells can be induced to acquire a new cell fate.

The research is published today in Developmental Cell.