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

Taty Anna Kamarudin, Sanja Bojic, Joseph Collin, Min Yu, Sameer Alharthi, Harley Buck, Alex Shortt, Lyle Armstrong, Francisco C. Figueiredo, Majlinda Lako

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 β 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.

Original languageEnglish
JournalStem Cells
DOIs
Publication statusAccepted/In press - 1 Jan 2017
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Bone Morphogenetic Proteins
Stem Cells
Epithelial Cells
Bone Morphogenetic Protein 4
Cell Line
Growth Inhibitors
Corneal Epithelium
Transforming Growth Factors
Tretinoin
Epidermal Growth Factor
Cornea
Retina
Cell Differentiation
Collagen
Transplantation
Light
Therapeutics

Keywords

  • Bone morphogenetic protein 4
  • Corneal epithelial cells
  • Corneal epithelial progenitors
  • Epidermal growth factor
  • Human embryonic stem cell
  • Human induced pluripotent stem cell
  • Retinoic acid

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

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. / Kamarudin, Taty Anna; Bojic, Sanja; Collin, Joseph; Yu, Min; Alharthi, Sameer; Buck, Harley; Shortt, Alex; Armstrong, Lyle; Figueiredo, Francisco C.; Lako, Majlinda.

In: Stem Cells, 01.01.2017.

Research output: Contribution to journalArticle

Kamarudin, Taty Anna ; Bojic, Sanja ; Collin, Joseph ; Yu, Min ; Alharthi, Sameer ; Buck, Harley ; Shortt, Alex ; Armstrong, Lyle ; Figueiredo, Francisco C. ; Lako, Majlinda. / 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. In: Stem Cells. 2017.
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AU - Alharthi, Sameer

AU - Buck, Harley

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AU - Armstrong, Lyle

AU - Figueiredo, Francisco C.

AU - Lako, Majlinda

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