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Induced Pluripotent Stem Cell-Derived Corneal Cells: Current Status and Application

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Abstract

Deficiency and dysfunction of corneal cells leads to the blindness observed in corneal diseases such as limbal stem cell deficiency (LSCD) and bullous keratopathy. Regenerative cell therapies and engineered corneal tissue are promising treatments for these diseases [1]. However, these treatments are not yet clinically feasible due to inadequate cell sources. The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka has provided a multitude of opportunities in research because iPSCs can be generated from somatic cells, thus providing an autologous and unlimited source for corneal cells. Compared to other stem cell sources such as mesenchymal and embryonic, iPSCs have advantages in differentiation potential and ethical concerns, respectively. Efforts have been made to use iPSCs to model corneal disorders and diseases, drug testing [2], and regenerative medicine [1]. Autologous treatments based on iPSCs can be exorbitantly expensive and time-consuming, but development of stem cell banks with human leukocyte antigen (HLA)- homozygous cell lines can provide cost- and time-efficient allogeneic alternatives. In this review, we discuss the early development of the cornea because protocols differentiating iPSCs toward corneal lineages rely heavily upon recapitulating this development. Differentiation of iPSCs toward corneal cell phenotypes have been analyzed with an emphasis on feeder-free, xeno-free, and well-defined protocols, which have clinical relevance. The application, challenges, and potential of iPSCs in corneal research are also discussed with a focus on hurdles that prevent clinical translation.

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Abbreviations

AQP1:

Aquaporin 1

bFGF:

Basic fibroblast growth factor

BMP:

Bone morphogenetic protein

CEndoC:

Corneal endothelial cells

CEpiC:

Corneal epithelial cells

CGMP:

Current Good Manufacturing Practices

CK:

Cytokeratin

CLAU:

Conjunctival Limbal Autograft

CLET:

Cultivated Limbal Epithelial Transplantation

Dkk2:

Dickkopf WNT Signaling Pathway Inhibitor 2

EGF:

Epidermal growth factor

ESC:

Embryonic stem cells

FACS:

Fluorescence-activated cell sorting

FGF:

Fibroblast growth factor

HLA:

Human leukocyte antigen

iPSCs:

Induced pluripotent stem cells

LSC:

Limbal stem cell

LSCD:

Limbal stem cell deficiency

MACS:

Magnetic cell sorting

NCC:

Neural crest cells

PDGF-BB:

Platelet-derived growth factor B

SEAM:

Self-formed ectodermal autonomous multi-zones

SLC4A11:

Solute carrier family 4-member 11

SLC4A4:

Sodium bicarbonate cotransporter 1

SLET:

Simple Limbal Epithelial Transplantation

TGF-β:

Transforming growth factor beta

Wnt:

Wingless-related integration site

ZO-1:

Zonula occludens-1

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Funding

This work was supported by the Wilson College of Textiles (JMG), the Department of Textile Engineering, Chemistry and Science (JMG), North Carolina Textile Foundation-Wilson College Fellowship (NM), NCSU Provost’s Fellowship (TCS). Graphics were created with BioRender.

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  1. Department of Textile Engineering, Chemistry, and Science, Wilson College of Textiles, North Carolina State University, Raleigh, NC, 27606, USA

    Nasif Mahmood, Taylor Cook Suh, Kiran M. Ali, Eelya Sefat, Ummay Mowshome Jahan, Yihan Huang & Jessica M. Gluck

  2. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA

    Brian C. Gilger

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Mahmood, N., Suh, T.C., Ali, K.M. et al. Induced Pluripotent Stem Cell-Derived Corneal Cells: Current Status and Application. Stem Cell Rev and Rep 18, 2817–2832 (2022). https://doi.org/10.1007/s12015-022-10435-8

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