Evaluation of the Suitability of Biocompatible Carriers as Artificial Transplants Using Cultured Porcine Corneal Endothelial Cells

Spinozzi, Daniele; Miron, Alina; Bruinsma, Marieke; Dapena, Isabel; Lavy, Itay; Binder, Perry S.; Rafat, Mehrdad; Oellerich, Silke; Melles, Gerrit R.J.

doi:10.1080/02713683.2018.1536215

Cited by 21 publications

(23 citation statements)

References 29 publications

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“…Preclinical studies using appropriate animal models are required to examine the safety and efficacy of these tissueengineered CEC-like grafts. This can be performed akin to the standard DSEAK and DMEK procedures using variously described carriers [25,98,99] or via simple cell injection [30,100]. Before animal studies, the differentiated cells must be examined for CEC marker expression, since there is a substantial chance of cellular heterogeneity in non-optimal cultures.…”

Section: Perspective and Challengesmentioning

confidence: 99%

Regenerative capacity of the corneal transition zone for endothelial cell therapy

et al. 2020

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The corneal endothelium located on the posterior corneal surface is responsible for regulating stromal hydration. This is contributed by a monolayer of corneal endothelial cells (CECs), which are metabolically active in a continuous fluid-coupled efflux of ions from the corneal stroma into the aqueous humor, preventing stromal over-hydration and preserving the orderly arrangement of stromal collagen fibrils, which is essential for corneal transparency. Mature CECs do not have regenerative capacity and cell loss due to aging and diseases results in irreversible stromal edema and a loss of corneal clarity. The current gold standard of treatment for this worldwide blindness caused by corneal endothelial failure is the corneal transplantation using cadaveric donor corneas. The top indication is Fuchs corneal endothelial dystrophy/degeneration, which represents 39% of all corneal transplants performed. However, the global shortage of transplantable donor corneas has restricted the treatment outcomes, hence instigating a need to research for alternative therapies. One such avenue is the CEC regeneration from endothelial progenitors, which have been identified in the peripheral endothelium and the adjacent transition zone. This review examines the evidence supporting the existence of endothelial progenitors in the posterior limbus and summarizes the existing knowledge on the microanatomy of the transitional zone. We give an overview of the isolation and ex vivo propagation of human endothelial progenitors in the transition zone, and their growth and differentiation capacity to the corneal endothelium. Transplanting these bioengineered constructs into in vivo models of corneal endothelial degeneration will prove the efficacy and viability, and the long-term maintenance of functional endothelium. This will develop a novel regenerative therapy for the management of corneal endothelial diseases.

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Section: Perspective and Challengesmentioning

confidence: 99%

Regenerative capacity of the corneal transition zone for endothelial cell therapy

et al. 2020

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“…In vitro surgical procedure was performed similar to a standard DMEK surgery 31 with some modifications as described previously 27 . In brief, three side ports were made at 2, 7, and 10 o’clock limbus-side, the artificial AC was filled with PBS, and a 3-mm main incision was made at 12 o’clock.…”

Section: Methodsmentioning

confidence: 99%

In Vitro Evaluation and Transplantation of Human Corneal Endothelial Cells Cultured on Biocompatible Carriers

et al. 2020

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Corneal transplantation is currently the only effective treatment option for dysfunctional corneal endothelial cells (CEC). In this study, we test in vitro the surgical potential of cultivated human corneal endothelial cells (hCEC) on human anterior lens capsule (HALC), LinkCell™ bioengineered collagen sheets of 20-µm thickness (LK20), and denuded Descemet membrane (dDM) as tissue-engineered grafts for Descemet membrane (DM) endothelial keratoplasty (DMEK) to bypass the problem of donor tissue availability. Primary hCEC cultured on all carriers formed a monolayer of tightly packed cells with a high cell viability rate (96% ± 4%). hCEC on HALC and LK20 showed unremarkable expression of zonula occludens-1 (ZO-1) and Na+/K+-adenosine triphosphatase (ATPase), while Na+/K+-ATPase expression of cells seeded on dDM was mainly cytoplasmic. All hCEC–carrier constructs were evaluated by simulating DMEK surgery in vitro using a human donor cornea without DM mounted on an artificial anterior chamber (AC) and a regular DMEK-graft used as a surgical reference model. During in vitro surgery, hCEC–HALC constructs behaved most similarly to a DMEK-graft during implantation and unfolding, showing good adhesion to the bare stroma. On the other hand, hCEC–LK20 and hCEC–dDM constructs required some additional handling because of challenges related to the surgical procedure, although they were both successfully unfolded and implanted in the artificial AC. The hCEC–dDM constructs showed similar graft adherence as hCEC–HALC constructs, while adherence of hCEC–LK20 constructs was less effective. After the in vitro surgery, the estimated area populated by viable cells on the hCEC–HALC and hCEC–LK20 constructs was ∼83% and ∼67%, respectively. Overall, hCEC–HALC constructs behaved most similarly to a DMEK-graft during in vitro DMEK surgery, while graft adhesion and surgical handling, respectively, are parameters still requiring optimization for hCEC–LK20 and hCEC–dDM constructs.

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“…A more recent study looked at HALCs as carriers for cultivated porcine CECs. 55 The cells formed a monolayer of hexagonal, tightly packed cells that expressed ZO-1 and Na + /K + -ATPase. In this study they also analyzed the handling ability of the grafts using a clinically applicable method.…”

Section: Biologically Derived Materialsmentioning

confidence: 99%

Biomaterials for corneal endothelial cell culture and tissue engineering

et al. 2021

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The corneal endothelium is the posterior monolayer of cells that are responsible for maintaining overall transparency of the avascular corneal tissue via pump function. These cells are non-regenerative in vivo and therefore, approximately 40% of corneal transplants undertaken worldwide are a result of damage or dysfunction of endothelial cells. The number of available corneal donor tissues is limited worldwide, hence, cultivation of human corneal endothelial cells (hCECs) in vitro has been attempted in order to produce tissue engineered corneal endothelial grafts. Researchers have attempted to recreate the current gold standard treatment of replacing the endothelial layer with accompanying Descemet’s membrane or a small portion of stroma as support with tissue engineering strategies using various substrates of both biologically derived and synthetic origin. Here we review the potential biomaterials that are currently in development to support the transplantation of a cultured monolayer of hCECs.

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Evaluation of the Suitability of Biocompatible Carriers as Artificial Transplants Using Cultured Porcine Corneal Endothelial Cells

Cited by 21 publications

References 29 publications

Regenerative capacity of the corneal transition zone for endothelial cell therapy

Regenerative capacity of the corneal transition zone for endothelial cell therapy

In Vitro Evaluation and Transplantation of Human Corneal Endothelial Cells Cultured on Biocompatible Carriers

Biomaterials for corneal endothelial cell culture and tissue engineering

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