4.6 Article

Treatment of corneal endothelial damage in a rabbit model with a bioengineered graft using human decellularized corneal lamina and cultured human corneal endothelium

Journal

PLOS ONE
Volume 14, Issue 11, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0225480

Keywords

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Funding

  1. Ministry of Health and Social Politics, Spain [EC-11, PI15/01447]
  2. Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016) [PI15/01447]
  3. European Development Regional Fund A way to achieve Europe (ERDF)
  4. Roche Farma SA
  5. Ministry of Education, Culture and Sports, Spain [AP2010-0659]
  6. BioMedical Foundation Mutua Madrilena, Spain
  7. BioMedical Foundation Marato TV3, Spain
  8. Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid
  9. Fondo Social Europeo (Programa Operativo de Empleo Juvenil, and Iniciativa de Empleo Juvenil (YEI)) [PEJ15/BIO/AI/0045, PEJD-2018-PRE/BMD-8878, PEJ15/BIO/AI/0093, PEJD-2018-PRE/BMD-9040]

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Objective We aimed to investigate the functionality of human decellularized stromal laminas seeded with cultured human corneal endothelial cells as a tissue engineered endothelial graft (TEEK) construct to perform endothelial keratoplasty in an animal model of corneal endothelial damage. Methods Engineered corneal endothelial grafts were constructed by seeding cultured human corneal endothelial cell (hCEC) suspensions onto decellularized human corneal stromal laminas with various coatings. The functionality and survival of these grafts with cultured hCECs was examined in a rabbit model of corneal endothelial damage after central descemetorhexis. Rabbits received laminas with and without hCECs (TEEK and control group, respectively). Results hCEC seeding over fibronectin-coated laminas provided an optimal and consistent endothelial cell count density and polygonal shape on the decellularized laminas, showing active pump fuction. Surgery was performed uneventfully as standard Descemet stripping automated endothelial keratoplasty (DSAEK). Corneal transparency gradually recovered in the TEEK group, whereas haze and edema persisted for up to 4 weeks in the controls. Histologic examination showed endothelial cells of human origin covering the posterior surface of the graft in the TEEK group. Conclusions Grafting of decellularized stroma carriers re-surfaced with human corneal endothelial cells ex vivo can be a readily translatable method to improve visual quality in corneal endothelial diseases.

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