Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liv...

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Main Authors: Irit Meivar-Levy, Tamar Sapir, Dana Berneman, Tal Weissbach, Sylvie Polak-Charcon, Philippe Ravassard, Andreas G. Tzakis, Eytan Mor, Camillo Ricordi, Sarah Ferber
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Journal of Transplantation
Online Access:http://dx.doi.org/10.1155/2011/252387
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author Irit Meivar-Levy
Tamar Sapir
Dana Berneman
Tal Weissbach
Sylvie Polak-Charcon
Philippe Ravassard
Andreas G. Tzakis
Eytan Mor
Camillo Ricordi
Sarah Ferber
author_facet Irit Meivar-Levy
Tamar Sapir
Dana Berneman
Tal Weissbach
Sylvie Polak-Charcon
Philippe Ravassard
Andreas G. Tzakis
Eytan Mor
Camillo Ricordi
Sarah Ferber
author_sort Irit Meivar-Levy
collection DOAJ
description Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.
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institution Kabale University
issn 2090-0007
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language English
publishDate 2011-01-01
publisher Wiley
record_format Article
series Journal of Transplantation
spelling doaj-art-25f5e41d67014ff0b5217d8c87dfc3e82025-02-03T06:07:49ZengWileyJournal of Transplantation2090-00072090-00152011-01-01201110.1155/2011/252387252387Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing CellsIrit Meivar-Levy0Tamar Sapir1Dana Berneman2Tal Weissbach3Sylvie Polak-Charcon4Philippe Ravassard5Andreas G. Tzakis6Eytan Mor7Camillo Ricordi8Sarah Ferber9Sheba Regenerative Medicine, Stem cells and Tissue engineering Center, Sheba Medical Center, Tel-Hashomer 52621, IsraelDiabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USASheba Regenerative Medicine, Stem cells and Tissue engineering Center, Sheba Medical Center, Tel-Hashomer 52621, IsraelObstetrics and Gynecology Department, Sapir Medical Ctrter 44281 Kfar Saba, IsraelThe Institute for Pathology, Sheba Medical Center, 52621 Tel-Hashomer, IsraelBiotechnology and Biotherapy Group, Centre de Recherche, Institut du Cerveau et de la Moelle CNRS UMR7225, INSERM UMRS795, Université Pierre et Marie Curie, 75005 Paris, FranceThe Miami Transplant Institute, University of Miami Leonard M. Miller School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USARabin Medical Center, Beilinson Campus, 49100 Petah-Tiqva, IsraelDiabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USASheba Regenerative Medicine, Stem cells and Tissue engineering Center, Sheba Medical Center, Tel-Hashomer 52621, IsraelActivation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.http://dx.doi.org/10.1155/2011/252387
spellingShingle Irit Meivar-Levy
Tamar Sapir
Dana Berneman
Tal Weissbach
Sylvie Polak-Charcon
Philippe Ravassard
Andreas G. Tzakis
Eytan Mor
Camillo Ricordi
Sarah Ferber
Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells
Journal of Transplantation
title Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells
title_full Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells
title_fullStr Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells
title_full_unstemmed Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells
title_short Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells
title_sort human liver cells expressing albumin and mesenchymal characteristics give rise to insulin producing cells
url http://dx.doi.org/10.1155/2011/252387
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