NORMALIZATION OF CULTURE OF CORNEAL ENDOTHELIAL CELLS
The present invention provides a method for the normalized culturing of corneal endothelial cells. More specifically, the present invention provides a culture-normalizing-agent of a corneal endothelial cell, comprising a fibrosis inhibitor. In detail, the present invention provides a culture-normalizing agent comprising a transforming growth factor (TGF) β signal inhibitor. The present invention also provides a culture medium for culturing a corneal endothelial cell normally, which comprises the culture-normalizing agent according to the present invention and corneal endothelium culture components. The present invention also provides a method for culturing a corneal endothelial cell normally, comprising the step of culturing a corneal endothelial cell using the culture-normalizing agent according to the present invention or the culture medium according to the present invention.
1 . A method for maintaining a cellular function of a corneal endothelial cell without inducing a transformation of the corneal endothelial cell into a fibroblastic phenotype, comprising a step of culturing a corneal endothelial cell using a culture normalizing agent comprising a fibrosis inhibitor, wherein said fibrosis inhibitor comprises a p38 MAP kinase inhibitor.
2 . The method according to claim 1 , wherein the p38 MAP kinase inhibitor is 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazole-5-yl]pyridine or a pharmaceutically acceptable salt thereof.
3 . The method according to claim 1 , wherein said method is for manufacturing a cell for transplantation which adapts to corneal transplantation.
4 . The method according to claim 3 , wherein said cell for transplantation is a cell of a primate.
5 . The method according to claim 3 , wherein said cell for transplantation is a cell of a human.
6 . The method according to claim 1 , further comprising adding a cell adhesion promoting agent to said corneal endothelial cell.
7 . The method according to claim 6 , wherein said cell adhesion promoting agent comprises
(R)-(+)-trans-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.
8 . The method according to claim 6 , wherein said fibrosis inhibitor is present at all times during the culturing of said corneal endothelial cell, while said cell adhesion promoting agent is present for a certain period of time, subsequently is removed so as to not be present for a certain period of time, and then is added to be present for a certain period of time during the culturing of said corneal endothelial cell.
9 . The method according to claim 6 , wherein both of said fibrosis inhibitor and said cell adhesion promoting agent are allowed to be present at all times during the culturing of said corneal endothelial cell.
10 . The method according to claim 1 , wherein the corneal endothelial cell is cultured using a culture medium comprising the culture normalizing agent and a culturing ingredient of corneal endothelium.