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Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. An open gate towards endogenous stem cell therapy in diabetes

maandag, 22 juni, 2009 - 16:00
Campus: Brussels Health Campus
Faculteit: Medicine and Pharmacy
auditorium R. Vanden Driessche
Xiaobo Xu
doctoraatsverdediging

Searching for pathways and mechanisms to boost
beta cell (re)generation in the adult pancreas as
a possibility to treat diabetes is the major topic of
this thesis. By applying a robust injury called
partial duct ligation (PDL), we induce generation
of new beta cells by increased beta cell cycle and
by the activation of the expression of
Neurogenin3, an master switch gene for
differentiation of embryonic islet cell progenitors.
Conditional knock-down of Ngn3 reduces beta cell
generation and lowers the beta cell cycle activity,
suggesting Ngn3-dependent beta cell neogenesis
in the adult mouse pancreas. Lineage tracing
shows that new islet cells originate from nonendocrine
Ngn3+ cells, located along the lining of
ducts and within islets. Ngn3+ cells can be
isolated from Ngn3-GFP promoter-reporter mice.
Comparison of their ultrastructure, global
transcriptome and in vitro differentiation
suggests a recapitulation of embryonic beta cell
formation in the adult, injured pancreas. Our data
provide the first direct evidence for the existence
of endogenous islet cell progenitors in the adult
mouse pancreas that may represent an obvious
target for therapeutic regeneration of beta cells in
diabetes.