Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers

Human corneal endothelial cells (HCEnCs) form a monolayer of hexagonal cells whose main function is to maintain corneal clarity by regulating corneal hydration. HCEnCs are derived from neural crest and are arrested in the post-mitotic state. Thus cell loss due to aging or corneal endothelial disorde...

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Main Authors: Schmedt, Thore, Chen, Yuming, Nguyen, Tracy T., Li, Shimin, Bonanno, Joseph A., Jurkunas, Ula V.
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528758/
id pubmed-3528758
recordtype oai_dc
spelling pubmed-35287582013-01-02 Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers Schmedt, Thore Chen, Yuming Nguyen, Tracy T. Li, Shimin Bonanno, Joseph A. Jurkunas, Ula V. Research Article Human corneal endothelial cells (HCEnCs) form a monolayer of hexagonal cells whose main function is to maintain corneal clarity by regulating corneal hydration. HCEnCs are derived from neural crest and are arrested in the post-mitotic state. Thus cell loss due to aging or corneal endothelial disorders leads to corneal edema and blindness–the leading indication for corneal transplantation. Here we show the existence of morphologically distinct subpopulations of HCEnCs that are interspersed among primary cells and exhibit enhanced self-renewal competence and lack of phenotypic signs of cellular senescence. Colonies of these uniform and hexagonal HCEnCs (HCEnC-21) were selectively isolated and demonstrated high proliferative potential that was dependent on endogenous upregulation of telomerase and cyclin D/CDK4. Further transduction of HCEnC-21 with telomerase yielded a highly proliferative corneal endothelial cell line (HCEnT-21T) that was devoid of oncogenic transformation and retained critical corneal endothelial cell characteristics and functionality. This study will significantly impact the fields of corneal cell biology and regenerative medicine. Public Library of Science 2012-12-21 /pmc/articles/PMC3528758/ /pubmed/23284695 http://dx.doi.org/10.1371/journal.pone.0051427 Text en © 2012 Schmedt 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 Schmedt, Thore
Chen, Yuming
Nguyen, Tracy T.
Li, Shimin
Bonanno, Joseph A.
Jurkunas, Ula V.
spellingShingle Schmedt, Thore
Chen, Yuming
Nguyen, Tracy T.
Li, Shimin
Bonanno, Joseph A.
Jurkunas, Ula V.
Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers
author_facet Schmedt, Thore
Chen, Yuming
Nguyen, Tracy T.
Li, Shimin
Bonanno, Joseph A.
Jurkunas, Ula V.
author_sort Schmedt, Thore
title Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers
title_short Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers
title_full Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers
title_fullStr Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers
title_full_unstemmed Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers
title_sort telomerase immortalization of human corneal endothelial cells yields functional hexagonal monolayers
description Human corneal endothelial cells (HCEnCs) form a monolayer of hexagonal cells whose main function is to maintain corneal clarity by regulating corneal hydration. HCEnCs are derived from neural crest and are arrested in the post-mitotic state. Thus cell loss due to aging or corneal endothelial disorders leads to corneal edema and blindness–the leading indication for corneal transplantation. Here we show the existence of morphologically distinct subpopulations of HCEnCs that are interspersed among primary cells and exhibit enhanced self-renewal competence and lack of phenotypic signs of cellular senescence. Colonies of these uniform and hexagonal HCEnCs (HCEnC-21) were selectively isolated and demonstrated high proliferative potential that was dependent on endogenous upregulation of telomerase and cyclin D/CDK4. Further transduction of HCEnC-21 with telomerase yielded a highly proliferative corneal endothelial cell line (HCEnT-21T) that was devoid of oncogenic transformation and retained critical corneal endothelial cell characteristics and functionality. This study will significantly impact the fields of corneal cell biology and regenerative medicine.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528758/
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