Tissue Engineering of the Corneal Endothelium: A Review of Carrier Materials

Teichmann, Juliane; Valtink, Monika; Nitschke, Mirko; Gramm, Stefan; Funk, Richard; Engelmann, Katrin; Werner, Carsten

doi:10.3390/jfb4040178

Cited by 34 publications

(19 citation statements)

References 197 publications

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“…In addition, we identified which previously reported markers represent the optimal markers for selection of high quality cultured CEnC, and propose TMEM178A as a novel positive selection marker. We propose that because senescent CEnC can be present in cultured CEnC preparations and that senescent cells may www.nature.com/scientificreports www.nature.com/scientificreports/ support tumorigenesis, a Descemet membrane biomimetic carrier is preferred to injection of a suspension of cells, to both maximize cell count and minimize their tumorigenic potential [62][63][64] . In conclusion, while additional changes to the dual media method may improve the culturing of CEnC in vitro, we provide evidence that this method is preferred to continuous culture in mitogen-rich media.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

Frausto¹,

Swamy²,

Peh

et al. 2020

Sci Rep

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the advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured cenc across serial passages has not been performed. to this end, we compared two established cenc culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. expansion by continuous passaging induced replicative cell senescence. transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion. The corneal endothelium is a neuroectoderm-derived tissue that is located on the posterior surface of the cornea and is a semipermeable monolayer of mitotically inactive (i.e., quiescent) cells. A critical functional property of the corneal endothelium is to maintain the corneal stroma in a relatively dehydrated state. This process ensures that the collagen fibers of the stroma retain an ultrastructural organization essential for corneal transparency. The pump-leak hypothesis is believed to best explain the role that the endothelium plays in maintaining a relatively dehydrated stroma. Passive movement of water from the aqueous humor to the stroma (i.e., leak) and active transport of solutes (i.e., pump) in the opposite direction are regulated by the corneal endothelial cell (CEnC) barrier formation (i.e., tight junctions, cell adhesion) and expression of solute transporters (e.g., Na/K ATPases, SLC4A11) 1. Mutations in genes encoding solute transporters (e.g., SLC4A11) or other essential endothelial cell functions (e.g., ZEB1, TCF4) lead to stromal edema and loss of corneal clarity 2-5. In general, loss of barrier integrity, dysfunction of solute transporters or a significant decrease in CEnC density leads to the loss of corneal clarity that necessitates corneal transplantation. Endothelial cell failure constitutes the primary indication for corneal transplantation both worldwide and in the U.S., serving as the indication for 55% of all keratoplasty procedures performed in the US in 2018 6. While endothelial keratoplasty represents a significant advance in the surgical management of corneal endothelial dysfunction, a variety of associated intraoperative and postoperative complications, in addition to the low rates of donor corneal recovery and the lack of adequately trained surgeons in the majority of countries, have significantly limited the impact of endothelial keratoplasty on visual impairment due to corneal endothelial dysfunction worl...

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Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

Frausto¹,

Swamy²,

Peh

et al. 2020

Sci Rep

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“…The parameters for electrospinning collagen include voltage between 12 and 17 kV voltages, the flow rate of 0.5–1 mL/hr and 1800 rpm rotational speed, which resulted in the fabrication of aligned nanofibers. The third layer with PLGA was spun on aligned collagen nanofibers and the third layers completed with thickness between 500 and 600 μm to mimic natural corneal thickness (Teichmann et al, ). The major part of this thickness was aligned collagen nanofibers.…”

Section: Discussionmentioning

confidence: 99%

Design and characterization of biodegradable multi layered electrospun nanofibers for corneal tissue engineering applications

Arabpour

Baradaran‐Rafii

Bakhshaiesh

et al. 2019

J Biomedical Materials Res

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Tissue engineering is one of the most promising areas for treatment of various ophthalmic diseases particularly for patients who suffer from limbal stem cell deficiency and this is due to the lack of existence of appropriate matrix for stem cell regeneration. The aim of this research project is to design and fabricate triple layered electrospun nanofibers as a suitable corneal tissue engineering scaffold and the objective is to investigate and perform various in vitro tests to find the most optimum and suitable scaffold for this purpose. Electrospun scaffolds were prepared in three layers. Poly(D, L-lactide-co-glycolide; PLGA, 50:50) nanofibers were electrospun as outer and inner layers of the scaffold and aligned type I collagen nanofibers were electrospun in the middle layer. Furthermore, the scaffolds were cross-linked by 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide hydrochloride and glutaraldehyde.Structural, physical, and mechanical properties of scaffolds were investigated by using N 2 adsorption/desorption isotherms, Fourier transform infrared spectroscopy, contact angle measurement, tensile test, degradation, shrinkage analysis, and scanning electron microscopy (SEM). In addition, capability to support cell attachment and viability were characterized by SEM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and 4 0 ,6-diamidino-2-phenylindole staining. According to the result of Brunauer-Emmett-Teller analysis, specific surface area of electrospun scaffold was about 23.7 m 2 g -1 . Tensile tests on cross-linked scaffolds represented more

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“…In addition, we identified which previously reported markers represent the optimal markers for selection of high quality cultured CEnC, and propose TMEM178A as a novel positive selection marker. We propose that because senescent CEnC can be present in cultured CEnC preparations and that senescent cells may support tumorigenesis, a Descemet membrane biomimetic carrier is preferred to injection of a suspension of cells, to both maximize cell count and minimize their tumorigenic potential (Gutermuth et al, 2019; Kinoshita et al, 2018; Teichmann et al, 2013). In conclusion, while additional changes to the dual media method may improve the culturing of CEnC in vitro, we provide evidence that this method is preferred to continuous culture in mitogen-rich media.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

Frausto¹,

Swamy²,

Peh

et al. 2019

Preprint

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SUMMARYThe advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.

show abstract

Tissue Engineering of the Corneal Endothelium: A Review of Carrier Materials

Cited by 34 publications

References 197 publications

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

Design and characterization of biodegradable multi layered electrospun nanofibers for corneal tissue engineering applications

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

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