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Lookup NU author(s): Dr Sanja Bojic, Dr Joseph Collin, Dr Min Yu, Professor Lyle Armstrong, Professor Francisco FigueiredoORCiD, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Cornea is a clear outermost layer of the eye which enables transmission of light onto the retina. The transparent corneal epithelium is regenerated by limbal stem cells (LSCs), whose loss/dysfunction results in limbal stem cell deficiency (LSCD). Ex vivo expansion of autologous LSCs obtained from patient’s healthy eye followed by transplantation onto the LSCs damaged/deficient eye, has provided a successful treatment for unilateral LSCD. This however is not applicable to patient with total bilateral LSCD, where LSCs are lost/damaged from both eyes. We investigated the potential of human induced pluripotent stem cell (hiPSC) to differentiate into corneal epithelial like cells as a source of autologous stem cell treatment for patients with total bilateral LSCD. Our study showed that combined addition of bone morphogenetic protein 4 (BMP4), all trans-retinoic acid (RA) and epidermal growth factor (EGF) for the first nine days of differentiation followed by cell-replating on collagen-IV coated surfaces with a corneal-specific-epithelial cell media for an additional 11 days, resulted in step wise differentiation of human embryonic stem cells (hESC) to corneal epithelial progenitors and mature corneal epithelial like cells. We observed differences in the ability of hiPSC lines to undergo differentiation to corneal epithelial-like cells which were dependent on the level of endogenous BMP4 signalling and could be restored via the activation of this signalling pathway by a specific TGFβ inhibitor (SB431542). Together our data reveal a differential ability of hiPSC lines to generate corneal epithelial cells which is underlined by the activity of endogenous BMP signalling pathway.
Author(s): Kamarudin TA, Bojic S, Collin J, Yu M, Alharthi S, Buck H, Shortt A, Armstrong L, Figueiredo FC, Lako M
Publication type: Article
Publication status: Published
Journal: Stem Cells
Year: 2018
Volume: 36
Issue: 3
Pages: 337-348
Print publication date: 01/03/2018
Online publication date: 11/12/2017
Acceptance date: 15/11/2017
Date deposited: 16/11/2017
ISSN (print): 1066-5099
ISSN (electronic): 1549-4918
Publisher: Wiley
URL: https://doi.org/10.1002/stem.2750
DOI: 10.1002/stem.2750
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