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Umbilical Cord Lining Stem Cells as a Novel and Promising Source for Ocular Surface Regeneration

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Abstract

The stem cells involved in renewal of the corneal epithelium are located in the basal region of the limbus, a narrow transition zone surrounding the cornea. In many ocular surface disorders loss of these stem cells results in partial or complete vision loss. Conventional corneal transplant in these patients is associated with dismal results. Stem cell transplantation offers new hope to such patients. The umbilical cord is emerging as an important source of stem cells that may have potential clinical applications. There are advantages to the use of umbilical cord stem cells as these cells are less immunogenic, non-tumorigenic, highly proliferative and ethically acceptable. In this study, we have confirmed the expression of several putative limbal stem cell markers such as HES1, ABCG2, BMI1, CK15 as well as cell adhesion-associated molecules INTEGRIN-α6, -α9, -β1, COLLAGEN-IV and LAMININ in our recently characterized CLEC-muc population derived from human umbilical cord. Ex vivo expansion of these cells on a human amniotic membrane substrate formed a stratified cell sheet that similarly expresses some of these molecules as well as cornea-specific cytokeratins, CK3 and CK12. Transplantation of a bioengineered CLEC-muc sheet in limbal stem cell-deficient rabbit eyes resulted in regeneration of a smooth, clear corneal surface with phenotypic expression of the normal corneal-specific epithelial markers CK3, CK12 but not CK4 or CK1/10. Our results suggest that CLEC-muc is a novel stem cell that can be ex vivo expanded for corneal epithelial regeneration in the treatment of various eye diseases.

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Acknowledgements

We thank Dr. V.A.Varathi, Dr. M. Dong-Rui, L. Wing-Sum and Y. Sia-Wey for helping in animal studies. This study was supported by grants from Biomedical Research Council, Singapore (BMRC 04/1/35/19/302 and 07/1/35/19/536 to LPK Ang).

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The authors indicate no potential conflicts of interest.

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Authors and Affiliations

  1. Singapore Eye Research Institute, Singapore, Singapore

    Hasan Mahmud Reza, Boon-Yee Ng, Federico Luengo Gimeno & Leonard Pek-Kiang Ang

  2. Department of Surgery and Faculty of Dentistry, National University of Singapore, Singapore, Singapore

    Toan Thang Phan

  3. CellResearch Corporation Pte Ltd, Singapore, Singapore

    Toan Thang Phan

  4. Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Singapore

    Leonard Pek-Kiang Ang

  5. The Eye & Cornea Transplant Centre, Singapore, Singapore

    Leonard Pek-Kiang Ang

  6. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Leonard Pek-Kiang Ang

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  1. Hasan Mahmud Reza
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  2. Boon-Yee Ng
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  3. Federico Luengo Gimeno
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  5. Leonard Pek-Kiang Ang
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Correspondence to Leonard Pek-Kiang Ang.

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Reza, H.M., Ng, BY., Gimeno, F.L. et al. Umbilical Cord Lining Stem Cells as a Novel and Promising Source for Ocular Surface Regeneration. Stem Cell Rev and Rep 7, 935–947 (2011). https://doi.org/10.1007/s12015-011-9245-7

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  • DOI: https://doi.org/10.1007/s12015-011-9245-7

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