Liver to Pancreas Transdifferentiation

Current Diabetes Reports
Irit Meivar-Levy, Sarah Ferber

Abstract

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. 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. Future studies on liver to pancreas TD should include the maturation of TD cells by 3D culture, the resto...Continue Reading

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Citations

Jun 27, 2020·Nature Reviews. Endocrinology·Gopika G NairMatthias Hebrok
Feb 4, 2021·Regenerative Medicine·Razvan IacobIrinel Popescu
Nov 22, 2020·International Journal of Molecular Sciences·Felipe ArroyaveFernando Lizcano
May 11, 2021·International Journal of Surgery Case Reports·Hong Son TrinhThanh Khiem Nguyen

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