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Differences in the activity of endogenous BMP signalling impact on the ability of induced pluripotent stem cells to differentiate to corneal epithelial like cells

Lookup NU author(s): Dr Sanja Bojic, Dr Joseph Collin, Dr Min Yu, Professor Lyle Armstrong, Professor Francisco Figueiredo, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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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