Abstract
In 2013, a clinical trial was initiated to investigate cell therapy for the treatment of corneal endothelial decompensation. Cultivating human corneal endothelial cells (CECs) while maintaining their functional phenotype is challenging; therefore, establishment of a confirmed protocol is pivotal for obtaining approval from regulatory authorities for use of cellular therapy products. In this study, we evaluated organ culture (OC) as a storage method for donor corneas used as a raw material for establishing CEC cultures. OC allows storage of corneal tissue for conventional corneal transplantation at 31–37 °C for up to 5 weeks, whereas storage at 4 °C is limited to 2 weeks. We investigated 20 pairs of corneas: one cornea of each pair was stored in OC and the other in cold storage for one week before CEC culture. In 15/20 cases, the CECs assumed a hexagonal sheet-like monolayer structure and expressed endothelial function-related markers. CECs were also obtained from OC corneas that had been stored for 1 (n = 19) and 2 (n = 7) months. As a further test, CECs were cultivated from 5 OC corneas that had been transported from France to Japan. In all cases, these corneas, even after international transport, generated CECs that formed hexagonal monolayers with clinically applicable and sufficiently high cell densities. In conclusion, the CEC cultures required for endothelial cell therapy can be obtained from OC corneas without changing the standard storage operating procedures of the eye banks.
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I declare having full availability on data and material exposed in this work.
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Funding
This research was supported by Japan-France Integrated Action Program (SAKURA) from Japan Society for the Promotion of Science and by the Hubert-Curien Partnership (PHC), SAKURA 41024TE, Ministère des Affaires Etrangères et du Développement International, Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche.
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ZH, NO, NK, and GT conceived and designed the study. ZH and MN acquired data. ZH, NO, MS, YK, and GT analyzed and interpreted data. ZH, NO, and GT drafted the article. NO, PG, NK, and GT critically revised the article.
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He, Z., Okumura, N., Sato, M. et al. Corneal endothelial cell therapy: feasibility of cell culture from corneas stored in organ culture. Cell Tissue Bank 22, 551–562 (2021). https://doi.org/10.1007/s10561-021-09918-8
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DOI: https://doi.org/10.1007/s10561-021-09918-8