Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines

<p>Abstract</p> <p>To overcome loss of stem-like properties and spontaneous differentiation those hinder the expansion and application of human mesenchymal stem cells (hMSCs), we have clonally isolated permanent and stable human MSC lines by ectopic overexpression of primary cell c...

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Main Authors: Wang Hsei-Wei, Lee Yi-Ting, Liu Hwa-Chung, Chen Chun-Li, Tsai Chih-Chien, Hou Lein-Tuan, Hung Shih-Chieh
Format: Article
Language:English
Published: BMC 2010-07-01
Series:Journal of Biomedical Science
Online Access:http://www.jbiomedsci.com/content/17/1/64
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author Wang Hsei-Wei
Lee Yi-Ting
Liu Hwa-Chung
Chen Chun-Li
Tsai Chih-Chien
Hou Lein-Tuan
Hung Shih-Chieh
author_facet Wang Hsei-Wei
Lee Yi-Ting
Liu Hwa-Chung
Chen Chun-Li
Tsai Chih-Chien
Hou Lein-Tuan
Hung Shih-Chieh
author_sort Wang Hsei-Wei
collection DOAJ
description <p>Abstract</p> <p>To overcome loss of stem-like properties and spontaneous differentiation those hinder the expansion and application of human mesenchymal stem cells (hMSCs), we have clonally isolated permanent and stable human MSC lines by ectopic overexpression of primary cell cultures of hMSCs with HPV 16 E6E7 and human telomerase reverse transcriptase (hTERT) genes. These cells were found to have a differentiation potential far beyond the ordinary hMSCs. They expressed trophoectoderm and germline specific markers upon differentiation with BMP4 and retinoic acid, respectively. Furthermore, they displayed higher osteogenic and neural differentiation efficiency than primary hMSCs or hMSCs expressed HPV16 E6E7 alone with a decrease in methylation level as proven by a global CpG island methylation profile analysis. Notably, the demethylated CpG islands were highly associated with development and differentiation associated genes. Principal component analysis further pointed out the expression profile of the cells converged toward embryonic stem cells. These data demonstrate these cells not only are a useful tool for the studies of cell differentiation both for the mesenchymal and neurogenic lineages, but also provide a valuable source of cells for cell therapy studies in animal models of skeletal and neurological disorders.</p>
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spelling doaj.art-f81e96466a3542de83b21e780632f4b92022-12-22T03:07:18ZengBMCJournal of Biomedical Science1021-77701423-01272010-07-011716410.1186/1423-0127-17-64Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell linesWang Hsei-WeiLee Yi-TingLiu Hwa-ChungChen Chun-LiTsai Chih-ChienHou Lein-TuanHung Shih-Chieh<p>Abstract</p> <p>To overcome loss of stem-like properties and spontaneous differentiation those hinder the expansion and application of human mesenchymal stem cells (hMSCs), we have clonally isolated permanent and stable human MSC lines by ectopic overexpression of primary cell cultures of hMSCs with HPV 16 E6E7 and human telomerase reverse transcriptase (hTERT) genes. These cells were found to have a differentiation potential far beyond the ordinary hMSCs. They expressed trophoectoderm and germline specific markers upon differentiation with BMP4 and retinoic acid, respectively. Furthermore, they displayed higher osteogenic and neural differentiation efficiency than primary hMSCs or hMSCs expressed HPV16 E6E7 alone with a decrease in methylation level as proven by a global CpG island methylation profile analysis. Notably, the demethylated CpG islands were highly associated with development and differentiation associated genes. Principal component analysis further pointed out the expression profile of the cells converged toward embryonic stem cells. These data demonstrate these cells not only are a useful tool for the studies of cell differentiation both for the mesenchymal and neurogenic lineages, but also provide a valuable source of cells for cell therapy studies in animal models of skeletal and neurological disorders.</p>http://www.jbiomedsci.com/content/17/1/64
spellingShingle Wang Hsei-Wei
Lee Yi-Ting
Liu Hwa-Chung
Chen Chun-Li
Tsai Chih-Chien
Hou Lein-Tuan
Hung Shih-Chieh
Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
Journal of Biomedical Science
title Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
title_full Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
title_fullStr Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
title_full_unstemmed Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
title_short Overexpression of hTERT increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
title_sort overexpression of htert increases stem like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
url http://www.jbiomedsci.com/content/17/1/64
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AT liuhwachung overexpressionofhtertincreasesstemlikepropertiesanddecreasesspontaneousdifferentiationinhumanmesenchymalstemcelllines
AT chenchunli overexpressionofhtertincreasesstemlikepropertiesanddecreasesspontaneousdifferentiationinhumanmesenchymalstemcelllines
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