Generation of beta cells from acinar cells

Luc Baeyens, Ilse Rooman, Luc Bouwens

Onderzoeksoutput: Chapter


It is becoming increasingly clear that differentiated adult somatic cells retain the capacity to be reprogrammed
into other cell types. In the case of the pancreas, a switch from an acinar to a b-cell phenotype in vitro can be
induced by soluble agents, such as growth factors and cytokines. We found that the combination of epidermal
growth factor and leukemia inhibitory factor stimulated the transdifferentiation of rat acinar cells into b-cells in culture.
The transdifferentiation, or cellular reprogramming, appears to recapitulate embryonic events, such as expression
of the transcription factor NGN3, which is characteristic of pancreas proendocrine progenitor cells. The NOTCHsignaling
pathway, whose activity is normally restricted to embryonic pancreas development, is also reactivated
during transdifferentiation. Inhibition of this pathway in the same experimental model leads to further stimulation of
b-cell neogenesis from adult acinar cells. Engraftment of the acinar-derived b-cells results in correction of glycemia
in alloxan-diabetic mice. The phenotype of the transdifferentiated cells is stable in vivo, resulting in normal and safe
function following transplantation. This approach opens ways for b-cell replacement therapy by transplantation or
Originele taal-2English
TitelStem cell therapy for diabetes
RedacteurenS. Efrat
UitgeverijHumana Press
Aantal pagina's14
ISBN van geprinte versie978-1-60761-365-7
StatusPublished - 2010

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S. Efrat


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