Feeder-free differentiation of cells exhibiting characteristics of corneal endothelium from human induced pluripotent stem cells

Wagoner, Michael D.; Bohrer, Laura R.; Aldrich, Benjamin T.; Greiner, Mark A.; Mullins, Robert F.; Worthington, Kristan S.; Tucker, Budd A.; Wiley, Luke A

doi:10.1242/bio.032102

Cited by 50 publications

(65 citation statements)

References 59 publications

(85 reference statements)

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“…Since their first report in 2006, the reprogramming techniques have rapidly evolved and iPSCs have become a powerful "de-differentiated" cell type that can be deployed to generate specific cell lineages [85]. In corneal endothelial studies, iPSCs were reported to differentiate into CEC-like cells using a modified McCabe's protocol as described above [86]. Likewise, the chemically defined conditions using small molecules for "dual Smad inhibition" together with the modulations of BMP and Wnt pathways also generated cells displaying CEC-like features from iPSCs via NCC induction [87].…”

Section: Other Experimental Sources Of Corneal Endothelial Progenitorsmentioning

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: Other Experimental Sources Of Corneal Endothelial Progenitorsmentioning

confidence: 99%

Regenerative capacity of the corneal transition zone for endothelial cell therapy

et al. 2020

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“…DNA microarray analysis revealed a close similarity between their corneal endothelial cells and primary cultured human corneal endothelial cells. In addition, Wagoner et al were able to derive corneal endothelial-like cells from iPS cells by modified McCabe’s protocol [17].…”

Section: Introductionmentioning

confidence: 99%

Review: corneal endothelial cell derivation methods from ES/iPS cells

Hatou

Shimmura

2019

Inflamm Regener

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Globally, approximately 12.7 million people are awaiting a transplantation, while only 185,000 cases of corneal transplantation are performed in a year. Corneal endothelial dysfunction (bullous keratopathy) due to Fuchs’ corneal endothelial dystrophy, or insults associated with intraocular surgeries, shared half of all indications for corneal transplantation. Regenerative therapy for corneal endothelium independent of eye bank eyes has great importance to solve the large supply-demand mismatching in corneal transplantation and reduce the number of worldwide corneal blindness. If corneal endothelial cells could be derived from ES or iPS cells, these stem cells would be the ideal cell source for cell therapy treatment of bullous keratopathy. Four representative corneal endothelial cell derivation methods were reviewed. Components in earlier methods included lens epithelial cell-conditioned medium or fetal bovine serum, but the methods have been improved and materials have been chemically more defined over the years. Conditioned medium or serum is replaced to recombinant proteins and small molecule compounds. These improvements enabled to open the corneal endothelial developmental mechanisms, in which epithelial-mesenchymal and mesenchymal-endothelial transition by TGF beta, BMP, and Wnt signaling have important roles. The protocols are gradually approaching clinical application; however, proof of efficacy and safety of the cells by adequate animal models are the challenges for the future.

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“…As an alternative to primary culture of hCECs, scientists have explored the differentiation of pluripotent stem cells to hCECs. Nevertheless, such differentiation protocols are still at an early developmental stage and need further improvements to prove that the genotype, phenotype and functionality of the differentiated cells resembles that of native hCECs [14][15][16]. Overall, the challenges associated with the primary culture of hCECs remain a barrier to their therapeutic application.…”

Section: Introductionmentioning

confidence: 99%

Nanoscale Topographies for Corneal Endothelial Regeneration

et al. 2021

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The corneal endothelium is the innermost layer of the cornea that selectively pumps ions and metabolites and regulates the hydration level of the cornea, ensuring its transparency. Trauma or disease affecting human corneal endothelial cells (hCECs) can result in major imbalances of such transport activity with consequent deterioration or loss of vision. Since tissue transplantation from deceased donors is only available to a fraction of patients worldwide, alternative solutions are urgently needed. Cell therapy approaches, in particular by attempting to expand primary culture of hCECs in vitro, aim to tackle this issue. However, existing cell culture protocols result in limited expansion of this cell type. Recent studies in this field have shown that topographical features with specific dimensions and shapes could improve the efficacy of hCEC expansion. Therefore, potential solutions to overcome the limitation of the conventional culture of hCECs may include recreating nanometer scale topographies (nanotopographies) that mimic essential biophysical cues present in their native environment. In this review, we summarize the current knowledge and understanding of the effect of substrate topographies on the response of hCECs. Moreover, we also review the latest developments for the nanofabrication of such bio-instructive cell substrates.

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Feeder-free differentiation of cells exhibiting characteristics of corneal endothelium from human induced pluripotent stem cells

Cited by 50 publications

References 59 publications

Regenerative capacity of the corneal transition zone for endothelial cell therapy

Regenerative capacity of the corneal transition zone for endothelial cell therapy

Review: corneal endothelial cell derivation methods from ES/iPS cells

Nanoscale Topographies for Corneal Endothelial Regeneration

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