Transplantation of iPSC-derived corneal endothelial substitutes in a monkey corneal edema model

• Published in: Stem cell research Vol. 55; p. 102497
• Main Authors: Hatou, Shin, Sayano, Tomoko, Higa, Kazunari, Inagaki, Emi, Okano, Yuji, Sato, Yasunori, Okano, Hideyuki, Tsubota, Kazuo, Shimmura, Shigeto
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2021; Elsevier
• Subjects: Bullous keratopathy; Cell therapy; Cornea; iPS cells; Translational medicine; Transplantation; Cornea; Transplantation; Cell therapy; Bullous keratopathy; Translational medicine; iPS cells
• ISSN: 1873-5061; 1876-7753
• DOI: 10.1016/j.scr.2021.102497

[Display omitted] •Corneal endothelial-like cells (CECSi cells) from several iPS cell lines.•Cryopreserved and thawed CECSi cells, expressing N-cadherin and Na, K-ATPase.•Efficacy of thawed CECSi cell transplants with monkey cornea edema model. In order to provide regenerative therapy for millions of patients suffering from corneal blindness globally, we derived corneal endothelial cell substitute (CECSi) cells from induced pluripotent stem cells (iPSCs) to treat corneal edema due to endothelial dysfunction (bullous keratopathy). We developed an efficient xeno-free protocol to produce CECSi cells from both research grade (Ff-MH09s01 and Ff-I01s04) and clinical grade (QHJI01s04) iPSCs. CECSi cells formed a hexagonal confluent monolayer with Na, K-ATPase alpha 1 subunit expression (ATP1A1), tight junctions, N-cadherin adherence junction formation, and nuclear PITX2 expression, which are all characteristics of corneal endothelial cells. CECSi cells can be cryopreserved, and thawed CECSi cell suspensions also expressed N-cadherin and ATP1A1. Residual undifferentiated iPSCs in QHJI01s04-derived CECSi cells was below 0.01%. Frozen stocks of Ff-I01s04- and QHJI01s04-derived CECSi cells were transported, thawed and transplanted into a monkey corneal edema model. CECSi-transplanted eyes significantly reduced corneal edema compared to control group. Our results show a promising approach to provide bullous keratopathy patients with an iPS-cell-based cell therapy to recover useful vision.