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

TLDR

Pancreatic acinar cells have been proposed as progenitors for pancreatic islets, a notion that could significantly impact strategies to expand insulin‑producing β‑cell mass in diabetes patients. The study aimed to establish the first in vivo lineage‑tracing method to assess the plasticity of pancreatic acinar cells. To achieve this, the authors engineered an acinar‑cell–specific inducible Cre recombinase mouse, crossed it with a reporter strain, and administered tamoxifen to permanently label acinar cells and their progeny. The lineage tracing revealed that labeled acinar cells do not transdifferentiate into β cells in adult mice, yet they proliferate to regenerate acinar tissue after partial pancreatectomy, demonstrating that mature acinar cells possess facultative acinar but not endocrine progenitor capacity.

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.