Bioengineering of Human Corneal Endothelial Cells from Single- to Four-Dimensional Cultures

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CORNEA (T YAMAGUCHI, SECTION EDITOR)

Bioengineering of Human Corneal Endothelial Cells from Single- to Four-Dimensional Cultures Yu-Ting Tsao 1,2 & Chao-Min Cheng 2,3 & Wei-Chi Wu 1,4 & Hung-Chi Chen 1,3,4

# Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Purpose of Review To summarize the recent advances of clinical and preclinical studies for corneal endothelial tissue bioengineering. Recent Findings The challenges facing the generation of a clinical applicable corneal endothelial graft can be broadly classified into cell source selection, culture medium optimization, scaffold establishment, and the following three- and four-dimensional (4D) corneal construction. Based on the current advances in primary human corneal endothelial cell (HCEC) culture and good manufacturing practice (GMP)–compliant medium development, the first clinical trial of bioengineered HCEC injection therapy has been conducted with encouraging results. Other significant findings include the in vivo experiments of the stem cell–derived HCEC, the development of serum-, xeno-, and additive-free media, and the construction of 4D scaffold. Summary It can be anticipated that tissue engineering–based therapy toward corneal endothelial diseases will replace the current keratoplasty method as a promising treatment option in the near future. Keywords Bioengineering . Corneal endothelium . Tissue culture . Cell therapy . Culture medium . Scaffold

Introduction The cornea is a transparent tissue that covers the front of the eye and accounts for the major refractive power in the This article is part of the Topical Collection on Cornea * Hung-Chi Chen [email protected] Yu-Ting Tsao [email protected] Chao-Min Cheng [email protected] Wei-Chi Wu [email protected] 1

Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, No. 5, Fuxing Street, Guishan District, Taoyuan City 33305, Taiwan

2

Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan

3

Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taoyuan City, Taiwan

4

Department of Medicine, Chang Gung University College of Medicine, Taoyuan City, Taiwan

human eye [1]. The human cornea consists of 5 different layers including the epithelium (outermost layer), Bowman’s layer, stroma, Descemet’s membrane, and endothelium (the innermost layer). The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CEC) functioning as a permeability barrier of the cornea. It allows the transportation of nutrients from the aqueous humor to the superficial layers of the cornea and pumps the water to the opposite direction through the Na+/K+ATPase to maintain the corneal transparency [2]. Loss of corneal transparency affects millions of individuals worldwide and is the leading cause of corneal transplantation [3]. Diseases such as Fuchs endothelial corneal dystrophy (FECD), pseudophakic bullous keratopathy, congenital hereditary endothelial dystrophy, posterior polymorphous corneal dystrophy (PPCD)