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Induced Pluripotent Stem Cells in Epithelial Lamellar Keratoplasty

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Modern Keratoplasty

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

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Abstract

Limbal stem cell (LSC) transplantation is required to restore vision in patients suffering from limbal stem cell deficiency (LSCD). Unfortunately, autologous LSC transplantation is not always possible, and allogeneic LSC transplantation often leads to poor long-term outcomes, despite systemic immunosuppression. Induced pluripotent stem cells (iPSCs) represent an unlimited source of autologous cells and could be directed toward corneal epithelial differentiation, thus representing a promising alternative source of cells for corneal epithelial regeneration. In this chapter, we will summarize current methods for iPSC differentiation toward corneal and limbal epithelial cells. Two main strategies that are used for induction of corneal epithelial differentiation of iPSCs, alone or in combination, are mimicking the LSC niche environment (by using feeder cells or different extracellular protein matrix coatings as substrates for cell cultivation in combination with conditioned medium produced by corneal or limbal fibroblasts) or mimicking natural ocular surface development (by inducing a cascade of defined signals known to direct development of corneal epithelium). Although iPSC-derived corneal epithelial cell sheets were transplanted successfully in an experimentally induced animal model of LSCD, future transplantation in humans demands the development of safe and GMP-compliant differentiation protocols.

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Abbreviations

ATMP:

Advanced therapeutic medicinal products

CLET:

Cultivated limbal epithelial transplantation

ECM:

Extracellular matrix

EGF:

Epithelial growth factor

ESC:

Embryonic stem cells

FACS:

Fluorescence-activated cell sorting

FBS:

Fetal bovine serum

FGF:

Fibroblast growth factor

GMP:

Good manufacturing practice

HAM:

Human amniotic membrane

iPSC:

Induced pluripotent stem cells

KGF:

Keratinocyte growth factor

KRT:

Cytokeratin

LSC:

Limbal stem cells

LSCD:

Limbal stem cell deficiency

MSC:

Mesenchymal stem cells

MZOC:

Multizone ocular cells

PMC:

Post-mitotic cells

RA:

Trans-retinoic acid

RPE:

Retinal pigmented epithelium

SDIA:

Stromal cell-derived inducing activity

SEAM:

Self-formed ectodermal autonomous multizone

SLET:

Simple limbal epithelial transplantation

SMILE:

Small incision lenticule extraction

TAC:

Transient amplifying ell

TDC:

Terminally differentiated cells

TGF:

Transforming growth factor

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Authors and Affiliations

  1. Faculty of Medical Sciences, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK

    Sanja Bojic, Francisco Figueiredo & Majlinda Lako

  2. Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

    Francisco Figueiredo

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  1. Sanja Bojic
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  2. Francisco Figueiredo
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  3. Majlinda Lako
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Correspondence to Sanja Bojic .

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  1. Vissum Miranza, Miguel Hernández University, Alicante, Spain

    Jorge L. Alió

  2. Vissum-Instituto Oftalmologico de Alica, Miguel Hernandez University, Alicante, Alicante, Spain

    Jorge L. Alió del Barrio

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Bojic, S., Figueiredo, F., Lako, M. (2023). Induced Pluripotent Stem Cells in Epithelial Lamellar Keratoplasty. In: Alió, J.L., del Barrio, J.L.A. (eds) Modern Keratoplasty. Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-031-32408-6_16

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  • DOI: https://doi.org/10.1007/978-3-031-32408-6_16

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