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Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration
Biva M. Desai, Jennifer Oliver-Krasinski, Diva D. De Leon, Cyrus Farzad, Nankang Hong, Steven D. Leach, Doris A. Stoffers
Biva M. Desai, Jennifer Oliver-Krasinski, Diva D. De Leon, Cyrus Farzad, Nankang Hong, Steven D. Leach, Doris A. Stoffers
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Research Article

Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration

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Abstract

It has been suggested that pancreatic acinar cells can serve as progenitors for pancreatic islets, a concept with substantial implications for therapeutic efforts to increase insulin-producing β cell mass in patients with diabetes. We report what we believe to be the first in vivo lineage tracing approach to determine the plasticity potential of pancreatic acinar cells. We developed an acinar cell–specific inducible Cre recombinase transgenic mouse, which, when mated with a reporter strain and pulsed with tamoxifen, resulted in permanent and specific labeling of acinar cells and their progeny. During various time periods of observation and using several models to provoke injury, we failed to observe any chase of the labeled cells into the endocrine compartment, indicating that acinar cells do not normally transdifferentiate into islet β cells in vivo in adult mice. In contrast, we observed a substantial role for replication of preexisting acinar cells in the regeneration of new acinar cells after partial pancreatectomy. These results indicate that mature acinar cells harbor a facultative acinar but not endocrine progenitor capacity.

Authors

Biva M. Desai, Jennifer Oliver-Krasinski, Diva D. De Leon, Cyrus Farzad, Nankang Hong, Steven D. Leach, Doris A. Stoffers

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Figure 6

No evidence of acinar-to-islet transdifferentiation after cerulein-induced pancreatitis.

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No evidence of acinar-to-islet transdifferentiation after cerulein-induc...
ElastaseCreERT2Tg/+Rosa26r+/– mice were treated with TAM for 3 weeks by subcutaneous continuous delivery pellet and subjected to a 2-day course of serial cerulein injections as described in Methods. (A–C) Severe exocrine inflammation but intact islets were evident 1 day after the initiation of treatment (A and B), with histologic recovery by 7 days (C). Cerulein-treated mice were randomized to receive daily injections of vehicle or Ex-4 (1 nmol/kg body wt i.p.) on day 3, the time of maximal Notch activation. (D–F) Tissues were harvested on day 7, and β-galactosidase activity (blue stain) and insulin immunoreactivity (red stain) were visualized. (D) Pancreas from a control mouse that received only PBS vehicle. (E and F) Pancreata from cerulein-treated mice that received vehicle (E) or Ex-4 (F). Original magnification, ×200.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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