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Nat Biotechnol. 2014 Jan;32(1):76-83. doi: 10.1038/nbt.2747. Epub 2013 Nov 17.

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

Author information

1
1] Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium. [2] Diabetes Center, California Institute for Regenerative Medicine (CIRM), University of California San Francisco, San Francisco, California, USA.
2
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
3
The Institute for Medical Research Israel-Canada, The Hebrew University, Jerusalem, Israel.
4
Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.
5
Diabetes Center, California Institute for Regenerative Medicine (CIRM), University of California San Francisco, San Francisco, California, USA.
6
Department of Cell and Developmental Biology, Vanderbilt University Program in Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
7
Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
8
1] Institut d'Investigacions Biomediques August Pi i Sunyer, Hospital Clinic de Barcelona, Barcelona, Spain. [2] Imperial College London, London, UK.
9
Development and Stem Cells Program, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch, France.

Abstract

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.

Comment in

PMID:
24240391
PMCID:
PMC4096987
DOI:
10.1038/nbt.2747
[Indexed for MEDLINE]
Free PMC Article
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