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Engineering of Human Corneal Endothelial Grafts

  • Stem Cell Therapy (J. Goldberg, Section Editor)
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Abstract

Human corneal endothelial cells (HCEC) play a pivotal role in maintaining corneal transparency. Unlike in other species, HCEC are notorious for their limited proliferative capacity in vivo after diseases, injury, aging, and surgery. Persistent HCEC dysfunction leads to sight-threatening bullous keratopathy with either an insufficient cell density or retrocorneal membrane due to endothelial-mesenchymal transition (EMT). Presently, the only solution to restore vision in eyes inflicted with bullous keratopathy or retrocorneal membrane relies upon transplantation of a cadaver human donor cornea containing a healthy corneal endothelium. Due to a severe global shortage of donor corneas, in conjunction with an increasing trend toward endothelial keratoplasty, it is opportune to develop a tissue engineering strategy to produce HCEC grafts. Prior attempts of producing these grafts by unlocking the contact inhibition-mediated mitotic block using trypsin–EDTA and culturing of single HCEC in a bFGF-containing medium run the risk of losing the normal phenotype to EMT by activating canonical Wnt signaling and TGF-β signaling. Herein, we summarize our novel approach in engineering HCEC grafts based on selective activation of p120-Kaiso signaling that is coordinated with activation of Rho-ROCK-canonical BMP signaling to reprogram HCEC into neural crest progenitors. Successful commercialization of this engineering technology will not only fulfill the global unmet need but also encourage the scientific community to re-think how cell–cell junctions can be safely perturbed to uncover novel therapeutic potentials in other model systems.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. R&D Department, Tissue Tech, Inc., Ocular Surface Center, and Ocular Surface Research & Education Foundation, 7000 SW 97th Ave #212, Miami, FL, 33173, USA

    Ying-Ting Zhu, Sean Tighe, Shuang-Ling Chen & Scheffer C. G. Tseng

  2. Department of Ophthalmology, Loyola University at Chicago, 2160 1st Ave, Maywood, IL, 60153, USA

    Thomas John

  3. Department of Ophthalmology, University of Cincinnati, 2600 Clifton Ave, Cincinnati, OH, 45220, USA

    Winston Y. Kao

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  1. Ying-Ting Zhu
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  2. Sean Tighe
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  3. Shuang-Ling Chen
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  4. Thomas John
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  5. Winston Y. Kao
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  6. Scheffer C. G. Tseng
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Correspondence to Scheffer C. G. Tseng.

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Zhu, YT., Tighe, S., Chen, SL. et al. Engineering of Human Corneal Endothelial Grafts. Curr Ophthalmol Rep 3, 207–217 (2015). https://doi.org/10.1007/s40135-015-0077-5

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