Liver to Pancreas Transdifferentiation

Irit Meivar-Levy, Sarah Ferber*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Purpose of the Review: Here, we review recent findings in the field of generating insulin-producing cells by pancreatic transcription factor (pTF)-induced liver transdifferentiation (TD). TD is the direct conversion of functional cell types from one lineage to another without passing through an intermediate stage of pluripotency. We address potential reasons for the restricted efficiency of TD and suggest modalities to overcome these challenges, to bring TD closer to its clinical implementation in autologous cell replacement therapy for insulin-dependent diabetes. Recent Findings: Liver to pancreas TD is restricted to cells that are a priori predisposed to undergo the developmental process. In vivo, the predisposition of liver cells is affected by liver zonation and hepatic regeneration. The TD propensity of liver cells is related to permissive epigenome which could be extended to TD-resistant cells by specific soluble factors. An obligatory role for active Wnt signaling in continuously maintaining a “permissive” epigenome is suggested. Moreover, the restoration of the pancreatic niche and vasculature promotes the maturation of TD cells along the β cell function. Summary: Future studies on liver to pancreas TD should include the maturation of TD cells by 3D culture, the restoration of vasculature and the pancreatic niche, and the extension of TD propensity to TD-resistant cells by epigenetic modifications. Liver to pancreas TD is expected to result in the generation of custom-made “self” surrogate β cells for curing diabetes.

Original languageEnglish
Article number76
JournalCurrent Diabetes Reports
Volume19
Issue number9
DOIs
StatePublished - 1 Sep 2019

Keywords

  • 3D culture (three-dimensional spheroids)
  • Autologous insulin-producing cells (AIP cells)
  • Diabetes
  • Epigenetic modifications
  • Liver
  • Pancreatic transcription factors (pTFs)
  • Reprogramming
  • Transdifferentiation (TD)
  • Wnt signaling

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