Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential
In this study we describe the derivation and immunological characterization of a primary epithelial cell type from the human umbilical cord membrane. These cord lining epithelial cells (CLECs) expressed and/or secreted isoforms of the nonclassical human leukocyte antigen class I (HLA-1b) glycoprotei...
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doaj-72d8a900ec5c44b19e13a2e558c642992020-11-25T03:01:43ZengSAGE PublishingCell Transplantation0963-68971555-38922011-12-012010.3727/096368910X564085Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation PotentialYue Zhou0Shu Uin Gan1Gen Lin2Yan Ting Lim3Jeyakumar Masilamani4Fatimah Bte Mustafa5Meow Ling Phua6Laura Rivino7Toan Thang Phan8Kok Onn Lee9Roy Calne10Paul A. Macary11Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeImmunology Program and Department of Microbiology, Yong Loo Lin School of Medicine, Centre for Life Sciences, National University of Singapore, SingaporeGraduate School for Integrative Sciences and Engineering, National University of Singapore, SingaporeCellResearch Corporation, SingaporeImmunology Program and Department of Microbiology, Yong Loo Lin School of Medicine, Centre for Life Sciences, National University of Singapore, SingaporeImmunology Program and Department of Microbiology, Yong Loo Lin School of Medicine, Centre for Life Sciences, National University of Singapore, SingaporeImmunology Program and Department of Microbiology, Yong Loo Lin School of Medicine, Centre for Life Sciences, National University of Singapore, SingaporeCellResearch Corporation, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeImmunology Program and Department of Microbiology, Yong Loo Lin School of Medicine, Centre for Life Sciences, National University of Singapore, SingaporeIn this study we describe the derivation and immunological characterization of a primary epithelial cell type from the human umbilical cord membrane. These cord lining epithelial cells (CLECs) expressed and/or secreted isoforms of the nonclassical human leukocyte antigen class I (HLA-1b) glycoproteins, HLA-G and E. Conditioned media from CLECs inhibited mitogen-stimulated T-lymphocyte responses, and in a mixed leukocyte reaction (MLR) assay, cocultured CLECs inhibited allogeneic responses with a concomitant reduction in proinflammatory cytokines. Using a transwell coculture system, it was demonstrated that these immunoregulatory effects were mediated by soluble factors secreted by CLECs, in a dose-dependent manner. Functional studies using HLA-G blocking antibody showed that the effects of CLEC-secreted products could be inhibited, thus demonstrating a significant and important role for soluble HLA-G. In vivo, we show that transplanted CLECs could be maintained for extended periods in immunocompetent mice where xenorejection rapidly destroyed primary keratinocytes, a control human epithelial cell type. Additionally, CLECs delayed the rejection of keratinocytes and extended their survival when cotransplanted, indicating an ability to protect adjacent human cell types that would otherwise be rejected if transplanted alone. We also show that CLECs transduced with a modified human proinsulin gene were transplanted intraperitoneally into streptozotocin (STZ)-induced diabetic mice, resulting in significantly lower levels of serum glucose compared to control mice. This study has characterized the immunological properties of CLECs and tested a potential therapeutic application in the treatment of a type 1 diabetes mouse model.https://doi.org/10.3727/096368910X564085 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yue Zhou Shu Uin Gan Gen Lin Yan Ting Lim Jeyakumar Masilamani Fatimah Bte Mustafa Meow Ling Phua Laura Rivino Toan Thang Phan Kok Onn Lee Roy Calne Paul A. Macary |
spellingShingle |
Yue Zhou Shu Uin Gan Gen Lin Yan Ting Lim Jeyakumar Masilamani Fatimah Bte Mustafa Meow Ling Phua Laura Rivino Toan Thang Phan Kok Onn Lee Roy Calne Paul A. Macary Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential Cell Transplantation |
author_facet |
Yue Zhou Shu Uin Gan Gen Lin Yan Ting Lim Jeyakumar Masilamani Fatimah Bte Mustafa Meow Ling Phua Laura Rivino Toan Thang Phan Kok Onn Lee Roy Calne Paul A. Macary |
author_sort |
Yue Zhou |
title |
Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential |
title_short |
Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential |
title_full |
Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential |
title_fullStr |
Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential |
title_full_unstemmed |
Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential |
title_sort |
characterization of human umbilical cord lining-derived epithelial cells and transplantation potential |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2011-12-01 |
description |
In this study we describe the derivation and immunological characterization of a primary epithelial cell type from the human umbilical cord membrane. These cord lining epithelial cells (CLECs) expressed and/or secreted isoforms of the nonclassical human leukocyte antigen class I (HLA-1b) glycoproteins, HLA-G and E. Conditioned media from CLECs inhibited mitogen-stimulated T-lymphocyte responses, and in a mixed leukocyte reaction (MLR) assay, cocultured CLECs inhibited allogeneic responses with a concomitant reduction in proinflammatory cytokines. Using a transwell coculture system, it was demonstrated that these immunoregulatory effects were mediated by soluble factors secreted by CLECs, in a dose-dependent manner. Functional studies using HLA-G blocking antibody showed that the effects of CLEC-secreted products could be inhibited, thus demonstrating a significant and important role for soluble HLA-G. In vivo, we show that transplanted CLECs could be maintained for extended periods in immunocompetent mice where xenorejection rapidly destroyed primary keratinocytes, a control human epithelial cell type. Additionally, CLECs delayed the rejection of keratinocytes and extended their survival when cotransplanted, indicating an ability to protect adjacent human cell types that would otherwise be rejected if transplanted alone. We also show that CLECs transduced with a modified human proinsulin gene were transplanted intraperitoneally into streptozotocin (STZ)-induced diabetic mice, resulting in significantly lower levels of serum glucose compared to control mice. This study has characterized the immunological properties of CLECs and tested a potential therapeutic application in the treatment of a type 1 diabetes mouse model. |
url |
https://doi.org/10.3727/096368910X564085 |
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