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Transplantation of iPSC-derived corneal endothelial substitutes in a monkey corneal edema model.
Hatou, Shin; Sayano, Tomoko; Higa, Kazunari; Inagaki, Emi; Okano, Yuji; Sato, Yasunori; Okano, Hideyuki; Tsubota, Kazuo; Shimmura, Shigeto.
Afiliación
  • Hatou S; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; Cellusion Inc, Tokyo, Japan.
  • Sayano T; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; Cellusion Inc, Tokyo, Japan.
  • Higa K; Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan.
  • Inagaki E; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
  • Okano Y; Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
  • Sato Y; Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
  • Okano H; Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
  • Tsubota K; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
  • Shimmura S; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. Electronic address: shige.shimmura@keio.jp.
Stem Cell Res ; 55: 102497, 2021 08.
Article en En | MEDLINE | ID: mdl-34411973
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Edema Corneal / Células Madre Pluripotentes Inducidas Tipo de estudio: Guideline / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Stem Cell Res Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Edema Corneal / Células Madre Pluripotentes Inducidas Tipo de estudio: Guideline / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Stem Cell Res Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido