Differences in the Activity of Endogenous Bone Morphogenetic Protein Signaling Impact on the Ability of Induced Pluripotent Stem Cells to Differentiate to Corneal Epithelial-Like Cells
Authors
TATY ANNA KAMARUDIN, SANJA BOJIC, JOSEPH COLLIN, MIN YU, SAMEER ALHARTHI, HARLEY BUCK, ALEX SHORTT, LYLE ARMSTRONG, FRANCISCO C. FIGUEIREDO, MAJLINDA LAKO
Institution
Institute of Genetic Medicine, International Centre for Life, Newcastle University, Central Parkway, Newcastle upon Tyne, United Kingdom; Princess Al Jawhara Al-Brahim Center of Excellence in Research of Hereditary
Country
Germany
Year
2017
Journal
Stem Cells
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 LSCs 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. However, this 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
and epidermal growth factor for the first 9 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 BMP signaling and could be restored via the activation
of this signaling pathway by a specific transforming growth factor b 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 signaling pathway