Construction of tissue-engineered full-thickness cornea substitute using limbal epithelial cell-like and corneal endothelial cell-like cells derived from human embryonic stem cells

Zhang, Canwei; Du, Liqun; Sun, Peng; Shen, Lin; Zhu, Jing; Pang, Kunpeng; Wu, Xinyi

doi:10.1016/j.biomaterials.2017.02.003

Cited by 53 publications

(34 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A Chinese team from Shandong has demonstrated the ability to seed human embryonic stem cell (hESC)-derived limbal epithelial-like cells on one side of the porcine scaffold and hESC-derived corneal endothelial-like cells on the other. 42 After transplantation into rabbits, corneal transparency was gradually improved through 8 weeks of followup, although residual haze and neovascularization were present. Nevertheless, along with vessels and inflammatory cells, stromal cells were observed to repopulate the implanted porcine stroma at only 8 weeks post-implantation.…”

Section: Full-thickness Corneas Based On Porcine Corneal Stromamentioning

confidence: 99%

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Lagali

2019

Current Eye Research

View full text Add to dashboard Cite

The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or recellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed. ARTICLE HISTORY

show abstract

Section: Full-thickness Corneas Based On Porcine Corneal Stromamentioning

confidence: 99%

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Lagali

2019

Current Eye Research

View full text Add to dashboard Cite

show abstract

“…This is another issue with which we should deal. Since we have a mature technological process for fabricating scaffold materials [ 55 – 58 ], we will explore cultivating HCECs with serum-free medium and seeding them in the scaffold materials to construct a lamellar or full thickness tissue-engineered corneal substitute which may have good prospects in future clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Promoting the expansion and function of human corneal endothelial cells with an orbital adipose-derived stem cell-conditioned medium

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundCorneal endothelial dysfunction causes severe impairment of vision. The only solution is corneal transplantation. However, this treatment is hampered by a worldwide shortage of donor corneas. New therapies may replace the conventional donor corneal transplantation alongside the developments in regenerative medicine and tissue engineering, but sufficient functional corneal endothelial cells (CECs) are essential. The aim of this study was to promote the expansion and function of human corneal endothelial cells (HCECs) in vitro and in vivo.MethodsThe phenotypes of human orbital adipose-derived stem cells (OASCs) were detected by flow cytometry and immunofluorescence. HCECs were isolated and cultured using a conditioned medium obtained from OASCs (OASC-CM) in vitro. Related cell markers of HCECs were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence. The cell counting kit-8 (CCK-8) assay and the wound healing assay were performed to evaluate the proliferation ability of the cells. The cultured HCECs were then transplanted into rabbit and monkey corneal endothelial dysfunction models by cell injection.ResultsCD29, CD105, CD49e, CD166, and vimentin were highly expressed in cultured human OASCs. The CEC-relative markers zonula occludens-1 (ZO-1), Na+/K+ ATPase, N-cadherin, Col8a2, and SLC4A4 were expressed in HCECs cultured by OASC-CM. The HCECs were able to maintain polygonal cell morphology and good proliferative capacity. In animal experiments, corneal transparency was achieved after the injection of HCECs, which demonstrated the good repair capacity of the cells.ConclusionsThe proliferation abilities of the cells were significantly enhanced, and related functional markers were strongly positive, while HCEC morphology was maintained using OASC-CM. HCECs obtained some stem cell-like properties. This preclinical study confirmed the therapeutic ability of the HCECs in vivo. Our findings demonstrated that cultured HCECs with OASC-CM might be a promising source for research and clinical treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0737-5) contains supplementary material, which is available to authorized users.

show abstract

“…Primary epithelial cells have been found to proliferate slowly on silk films in the co-culture medium, thus requiring a high cell number/density at seeding. Furthermore, multi-layer stratification of the epithelial layer may require utilization of limbal epithelial stem cells with high proliferative capabilities, which may be derived from pluripotent stem cells (Mikhailova et al, 2016;Zhang et al, 2017).…”

Section: Of 36mentioning

confidence: 99%

Assembly and Application of a Three‐Dimensional Human Corneal Tissue Model

et al. 2019

View full text Add to dashboard Cite

The cornea provides a functional barrier separating the outside environment from the intraocular environment, thereby protecting posterior segments of the eye from infection and damage. Pathological changes that compromise the structure or integrity of the cornea may occur as a result of injury or disease and can lead to debilitating effects on visual acuity. Over 10 million people worldwide are visually impaired or blind due to corneal opacity. Thus, physiologically relevant in vitro approaches to predict corneal toxicity of chemicals or effective treatments for disease prior to ocular exposure, as well as to study the corneal effects of systemic, chronic conditions, such as diabetes, are needed to reduce use of animal testing and accelerate therapeutic development. We have previously bioengineered an innervated corneal tissue model using silk protein scaffolds to recapitulate the structural and mechanical elements of the anterior cornea and to model the functional aspects of corneal sensation with the inclusion of epithelial, stromal, and neural components. The purpose of this unit is to provide a step‐by‐step guide for preparation, assembly, and application of this three‐dimensional corneal tissue system to enable the study of corneal tissue biology. © 2019 by John Wiley & Sons, Inc.

show abstract

Construction of tissue-engineered full-thickness cornea substitute using limbal epithelial cell-like and corneal endothelial cell-like cells derived from human embryonic stem cells

Cited by 53 publications

References 57 publications

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Promoting the expansion and function of human corneal endothelial cells with an orbital adipose-derived stem cell-conditioned medium

Assembly and Application of a Three‐Dimensional Human Corneal Tissue Model

Contact Info

Product

Resources

About