Paracrine Secretion of Transforming Growth Factor β by Ductal Cells Promotes Acinar-to-Ductal Metaplasia in Cultured Human Exocrine Pancreas Tissues

Naoki Akanuma, Jun Liu, Geou Yarh Liou, Xue Yin, Kaitlyn R. Bejar, Chengyang Liu, Luzhe Sun, Peter Storz, Pei Wang

Research output: Contribution to journalArticle

2 Scopus citations


Objective We aimed to evaluate the contribution of acinar-to-ductal metaplasia (ADM) to the accumulation of cells with a ductal phenotype in cultured human exocrine pancreatic tissues and reveal the underlying mechanism. Methods We sorted and cultured viable cell populations in human exocrine pancreatic tissues with a flow cytometry-based lineage tracing method to evaluate possible mechanisms of ADM. Cell surface markers, gene expression pattern, and sphere formation assay were used to examine ADM. Results A large proportion of acinar cells gained CD133 expression during the 2-dimensional culture and showed down-regulation of acinar markers and up-regulation of ductal markers, assuming an ADM phenotype. In a serum-free culture condition, ADM induction was mainly dependent on transforming growth factor β (TGF-β) secreted from cultured ductal cells. Human acinar cells when cultured alone for a week in a serum-free condition do not undergo ADM. However, serum may contain other factors besides TGF-β to induce ADM in human acinar cells. In addition, we found that TGF-β cannot induce ADM of murine acinar cells. Conclusions Ductal cells are the major source of TGF-β that induces ADM in cultured human exocrine pancreatic tissues. This culture system might be a useful model to investigate the mechanism of ADM in human cells.

Original languageEnglish (US)
Pages (from-to)1202-1207
Number of pages6
Issue number9
StatePublished - Oct 1 2017



  • acinar cells
  • human
  • metaplasia
  • TGF-β

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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