Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice.

Baeyens L, Lemper M, Leuckx G, De Groef S, Bonfanti P, Stangé G, Shemer R, Nord C, Scheel DW, Pan FC, Ahlgren U, Gu G, Stoffers DA, Dor Y, Ferrer J, Gradwohl G, Wright CV, Van de Casteele M, German MS, Bouwens L, Heimberg H
Nat Biotechnol. 2014 32 (1): 76-83

PMID: 24240391 · PMCID: PMC4096987 · DOI:10.1038/nbt.2747

Reprogramming of pancreatic exocrine cells into cells resembling beta cells may provide a strategy for treating diabetes. Here we show that transient administration of epidermal growth factor and ciliary neurotrophic factor to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta-like cells are epigenetically reprogrammed, functional and glucose responsive, and they reinstate normal glycemic control for up to 248 d. The regenerative process depends on Stat3 signaling and requires a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. In contrast to previous work demonstrating in vivo conversion of acinar cells to beta-like cells by viral delivery of exogenous transcription factors, our approach achieves acinar-to-beta-cell reprogramming through transient cytokine exposure rather than genetic modification.

MeSH Terms (12)

Acinar Cells Animals Cell Differentiation Cell Proliferation Ciliary Neurotrophic Factor Diabetes Mellitus Epidermal Growth Factor Hyperglycemia Insulin-Secreting Cells Mice Mice, Inbred NOD Signal Transduction

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