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

Shin Hatou, Tomoko Sayano, Kazunari Higa, Emi Inagaki, Yuji Okano, Yasunori Sato, Hideyuki Okano, Kazuo Tsubota, Shigeto Shimmura

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Objective: 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). Methods and results: 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. Conclusion: Our results show a promising approach to provide bullous keratopathy patients with an iPS-cell-based cell therapy to recover useful vision.

本文言語English
論文番号102497
ジャーナルStem Cell Research
55
DOI
出版ステータスPublished - 2021 8月

ASJC Scopus subject areas

  • 発生生物学
  • 細胞生物学

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