Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening
This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progeniesas cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary...
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my.sunway.eprints.2652015-04-02T02:01:46Z http://eprints.sunway.edu.my/265/ Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening Vinoth, Kumar Jayaseelan Manikandan, Jayapal Sethu, Swaminathan Balakrishan, Lakshmidevi Heng, Alexis Boon Chin * Lu, Kai Hande, Manoor Prakash Cao, Tong QR Microbiology This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progeniesas cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of peripheral blood lymphocytes (PBL), upon exposure to Mitomycin C, gamma irradiation and H2O2. It was demonstrated that hESC-derived fibroblastic progenies (H1F) displayed significantly higher chromosomal aberrations, micronuclei formation and double strand break (DSB) formation, as compared toundifferentiated hESC upon exposure to genotoxic stress. Nevertheless, H1F cell types displayed comparable sensitivities to genotoxic challenge as HEPM and PBL, both of which are representative of somatic cell types commonly used for genotoxicity screening. Subsequently, transcriptomic and pathways analysis identified differential expression of critical genes involved in cell death and DNA damage response upon exposure to gamma irradiation. The results thus demonstrate that hESC-derived fibroblastic progenies are as sensitive as commonly-used somatic cell types for genotoxicity screening. Moreover, hESCs have additional advantages, such as their genetic normality compared to immortalized cell lines, as well as their amenability to scale-up for producing large, standardized quantities of cells for genotoxicity screening on an industrial scale, something which can never be achieved with primary cell cultures. Elsevier 2014-08-20 Article PeerReviewed Vinoth, Kumar Jayaseelan and Manikandan, Jayapal and Sethu, Swaminathan and Balakrishan, Lakshmidevi and Heng, Alexis Boon Chin * and Lu, Kai and Hande, Manoor Prakash and Cao, Tong (2014) Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening. Journal of Biotechnology, 184. pp. 154-168. ISSN 0168-1656 http://www.sciencedirect.com/science/article/pii/S0168165614002405 http://dx.doi.org/10.1016/j.jbiotec.2014.05.009 |
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QR Microbiology Vinoth, Kumar Jayaseelan Manikandan, Jayapal Sethu, Swaminathan Balakrishan, Lakshmidevi Heng, Alexis Boon Chin * Lu, Kai Hande, Manoor Prakash Cao, Tong Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening |
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This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progeniesas cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of peripheral blood lymphocytes (PBL), upon exposure to Mitomycin C, gamma irradiation and H2O2. It was demonstrated that hESC-derived fibroblastic progenies (H1F) displayed significantly higher chromosomal aberrations, micronuclei formation and double strand break (DSB) formation, as compared toundifferentiated hESC upon exposure to genotoxic stress. Nevertheless, H1F cell types displayed comparable sensitivities to genotoxic challenge as HEPM and PBL, both of which are representative of somatic cell types commonly used for genotoxicity screening. Subsequently, transcriptomic and pathways analysis identified differential expression of critical genes involved in cell death and DNA damage response upon exposure to gamma irradiation. The results thus demonstrate that hESC-derived fibroblastic progenies are as sensitive as commonly-used somatic cell types for genotoxicity screening. Moreover, hESCs have additional advantages, such as their genetic normality compared to immortalized cell lines, as well as their amenability to scale-up for producing large, standardized quantities of cells for genotoxicity screening on an industrial scale, something which can never be achieved with primary cell cultures. |
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Article |
author |
Vinoth, Kumar Jayaseelan Manikandan, Jayapal Sethu, Swaminathan Balakrishan, Lakshmidevi Heng, Alexis Boon Chin * Lu, Kai Hande, Manoor Prakash Cao, Tong |
author_facet |
Vinoth, Kumar Jayaseelan Manikandan, Jayapal Sethu, Swaminathan Balakrishan, Lakshmidevi Heng, Alexis Boon Chin * Lu, Kai Hande, Manoor Prakash Cao, Tong |
author_sort |
Vinoth, Kumar Jayaseelan |
title |
Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening |
title_short |
Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening |
title_full |
Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening |
title_fullStr |
Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening |
title_full_unstemmed |
Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening |
title_sort |
evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening |
publisher |
Elsevier |
publishDate |
2014 |
url |
http://eprints.sunway.edu.my/265/ http://www.sciencedirect.com/science/article/pii/S0168165614002405 http://dx.doi.org/10.1016/j.jbiotec.2014.05.009 |
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1644324284466724864 |
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13.1944895 |