Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2

Adipose tissue mesenchymal stem cells (ATMSCs) represent an attractive tool for the establishment of a successful stem cell-based therapy in the field of liver regeneration medicine. ATMSCs overexpressing Oct4 and Sox2 (Oct4/Sox2-ATMSCs) showed enhanced proliferation and multipotency. Hence, we hypo...

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Main Authors:	Han, Sei-Myoung, Coh, Ye-Rin, Ahn, Jin-Ok, Jang, Goo, Yum, Soo Young, Kang, Sung-Keun, Lee, Hee-Woo, Youn, Hwa-Young
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376765/

id	pubmed-4376765
recordtype	oai_dc
spelling	pubmed-43767652015-04-04 Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2 Han, Sei-Myoung Coh, Ye-Rin Ahn, Jin-Ok Jang, Goo Yum, Soo Young Kang, Sung-Keun Lee, Hee-Woo Youn, Hwa-Young Research Article Adipose tissue mesenchymal stem cells (ATMSCs) represent an attractive tool for the establishment of a successful stem cell-based therapy in the field of liver regeneration medicine. ATMSCs overexpressing Oct4 and Sox2 (Oct4/Sox2-ATMSCs) showed enhanced proliferation and multipotency. Hence, we hypothesized that Oct4 and Sox2 can increase “transdifferentiation” of ATMSCs into cells of the hepatic lineage. In this study, we generated Oct4- and Sox2-overexpressing human ATMSCs by liposomal transfection. We confirmed the expression of mesenchymal stem cell surface markers without morphological alterations in both red-fluorescent protein (RFP) (control)- and Oct4/Sox2-ATMSCs by flow cytometry. After induction of differentiation into hepatocyte-like cells, the morphology of ATMSCs changed and they began to appear as round or polygonal epithelioid cells. Hepatic markers were evaluated by reverse transcription-polymerase chain reaction and confirmed by immunofluorescence. The results showed that albumin was strongly expressed in hepatogenic differentiated Oct4/Sox2-ATMSCs, whereas the expression level of α-fetoprotein was lower than that of RFP-ATMSCs. The functionality of hepatocytes was evaluated by periodic acid-Schiff (PAS) staining and urea assays. The number of PAS-positive cells was significantly higher and urea production was significantly higher in Oct4/Sox2-ATMSCs compared to that in RFP-ATMSCs. Taken together, the hepatocyte-like cells derived from Oct4/Sox2-ATMSCs were mature hepatocytes, possibly functional hepatocytes with enhanced capacity to store glycogen and produce urea. In this study, we demonstrated the enhanced transdifferentiation of Oct4- and Sox2-overexpressing ATMSCs into hepatocyte-like cells that have enhanced hepatocyte-specific functions. Therefore, we expect that Oct4/Sox2-ATMSCs may become a very useful source for hepatocyte regeneration or liver cell transplantation. Public Library of Science 2015-03-27 /pmc/articles/PMC4376765/ /pubmed/25815812 http://dx.doi.org/10.1371/journal.pone.0108874 Text en © 2015 Han et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Han, Sei-Myoung Coh, Ye-Rin Ahn, Jin-Ok Jang, Goo Yum, Soo Young Kang, Sung-Keun Lee, Hee-Woo Youn, Hwa-Young
spellingShingle	Han, Sei-Myoung Coh, Ye-Rin Ahn, Jin-Ok Jang, Goo Yum, Soo Young Kang, Sung-Keun Lee, Hee-Woo Youn, Hwa-Young Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2
author_facet	Han, Sei-Myoung Coh, Ye-Rin Ahn, Jin-Ok Jang, Goo Yum, Soo Young Kang, Sung-Keun Lee, Hee-Woo Youn, Hwa-Young
author_sort	Han, Sei-Myoung
title	Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2
title_short	Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2
title_full	Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2
title_fullStr	Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2
title_full_unstemmed	Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2
title_sort	enhanced hepatogenic transdifferentiation of human adipose tissue mesenchymal stem cells by gene engineering with oct4 and sox2
description	Adipose tissue mesenchymal stem cells (ATMSCs) represent an attractive tool for the establishment of a successful stem cell-based therapy in the field of liver regeneration medicine. ATMSCs overexpressing Oct4 and Sox2 (Oct4/Sox2-ATMSCs) showed enhanced proliferation and multipotency. Hence, we hypothesized that Oct4 and Sox2 can increase “transdifferentiation” of ATMSCs into cells of the hepatic lineage. In this study, we generated Oct4- and Sox2-overexpressing human ATMSCs by liposomal transfection. We confirmed the expression of mesenchymal stem cell surface markers without morphological alterations in both red-fluorescent protein (RFP) (control)- and Oct4/Sox2-ATMSCs by flow cytometry. After induction of differentiation into hepatocyte-like cells, the morphology of ATMSCs changed and they began to appear as round or polygonal epithelioid cells. Hepatic markers were evaluated by reverse transcription-polymerase chain reaction and confirmed by immunofluorescence. The results showed that albumin was strongly expressed in hepatogenic differentiated Oct4/Sox2-ATMSCs, whereas the expression level of α-fetoprotein was lower than that of RFP-ATMSCs. The functionality of hepatocytes was evaluated by periodic acid-Schiff (PAS) staining and urea assays. The number of PAS-positive cells was significantly higher and urea production was significantly higher in Oct4/Sox2-ATMSCs compared to that in RFP-ATMSCs. Taken together, the hepatocyte-like cells derived from Oct4/Sox2-ATMSCs were mature hepatocytes, possibly functional hepatocytes with enhanced capacity to store glycogen and produce urea. In this study, we demonstrated the enhanced transdifferentiation of Oct4- and Sox2-overexpressing ATMSCs into hepatocyte-like cells that have enhanced hepatocyte-specific functions. Therefore, we expect that Oct4/Sox2-ATMSCs may become a very useful source for hepatocyte regeneration or liver cell transplantation.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376765/
_version_	1613204528618799104

Enhanced Hepatogenic Transdifferentiation of Human Adipose Tissue Mesenchymal Stem Cells by Gene Engineering with Oct4 and Sox2

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