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US 10,501,725 B2Granted
Method for producing therapeutic corneal endothelial substitute cell sphere
AssigneeKeio University
InventorsShigeto Shimmura, Shin Hatou, Kazuo Tsubota
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AssigneeKeio University
InventorsShigeto Shimmura, Shin Hatou, Kazuo Tsubota
Estimating the term…
The problem of the present invention is to provide a method of efficiently producing therapeutic alternative corneal endothelial cells, particularly, a method capable of stably producing them in a condition suitable for intraocular transplantation (in the anterior chamber) in a large amount. Furthermore, the present invention aims to provide a composition for transplantation, which is preferable for intraocular administration, particularly, into the anterior chamber. A therapeutic alternative corneal endothelial cell sphere can be produced by culturing stem cells in suspension in a differentiation induction medium containing a GSK3 inhibitor, retinoic acid and a ROCK inhibitor. Addition of a viscoelastic substance during intraocular (into the anterior chamber) transplantation of the sphere or cultured corneal endothelial cells dispersed into single cells can increase the number of adherent cells after transplantation.
A pharmaceutical composition for transplantation comprising a therapeutic corneal endothelial cell sphere suspension having a cell density of 1-5×106 cells/ml, and a viscoelastic substance, wherein the viscoelastic substance is 5-40 mg/ml hyaluronic acid and/or 5-50 mg/ml chondroitin sulfate, and wherein the ratio of viscoelastic substance:cell sphere suspension is 1:1 to 1:5.
A pharmaceutical composition for transplantation comprising a cultured corneal endothelial cell suspension having a cell density of 1-5 ×106 cells/ml, and a viscoelastic substance, wherein the cultured corneal endothelial cells are dispersed as single cells or in the form of a cell aggregate, wherein the viscoelastic substance is 5-40 mg/ml hyaluronic acid and/or 5-50 mg/ml chondroitin sulfate, and wherein the ratio of viscoelastic substance:cell suspension is 1:1 to 1:5.
A method for improving cell engraftment during transplantation, comprising transplanting a corneal endothelial cell composition comprising (a) a cultured corneal endothelial cell suspension having a cell density of 1-5×106 cells/ml and (b) a viscoelastic substance into an anterior chamber of an eye, wherein the viscoelastic substance is 5-40 mg/ml hyaluronic acid and/or 5-50 mg/ml chondroitin sulfate, wherein the cells are dispersed into single cells or used in the form of a cell aggregate, wherein the ratio of viscoelastic substance:cell suspension is 1:1 to 1:5.
Dependencies are inferred from the claim text.