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Current Diabetes Reports

Erschienen in:

01.09.2019 | Immunology, Transplantation, and Regenerative Medicine (L Piemonti and V Sordi, Section Editors)

Liver to Pancreas Transdifferentiation

verfasst von: Irit Meivar-Levy, Sarah Ferber

Erschienen in: Current Diabetes Reports | Ausgabe 9/2019

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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.

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Titel: Liver to Pancreas Transdifferentiation
verfasst von: Irit Meivar-Levy
Sarah Ferber
Publikationsdatum: 01.09.2019
Verlag: Springer US
Erschienen in: Current Diabetes Reports / Ausgabe 9/2019
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-019-1198-2

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