A ROCK Inhibitor Promotes Graft Survival during Transplantation of iPS-Cell-Derived Retinal Cells

Currently, retinal pigment epithelium (RPE) transplantation includes sheet and single-cell transplantation, the latter of which includes cell death and may be highly immunogenic, and there are some issues to be improved in single-cell transplantation. Y-27632 is an inhibitor of Rho-associated protei...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-03, Vol.22 (6), p.3237
Main Authors: Ishida, Masaaki, Sugita, Sunao, Makabe, Kenichi, Fujii, Shota, Futatsugi, Yoko, Kamao, Hiroyuki, Yamasaki, Suguru, Sakai, Noriko, Maeda, Akiko, Mandai, Michiko, Takahashi, Masayo
Format: Article
Language:English
Subjects:
Amides - pharmacology
Animals
Apoptosis - drug effects
Biomarkers
Cell Adhesion - drug effects
Cell Proliferation - drug effects
Cells, Cultured
Cytokines - metabolism
Graft Survival - drug effects
Humans
Immunohistochemistry
Induced Pluripotent Stem Cells - cytology
Inflammation Mediators - metabolism
iPS cells
Macaca fascicularis
Protein Kinase Inhibitors - pharmacology
Pyridines - pharmacology
retinal pigment epithelium
Retinal Pigment Epithelium - drug effects
Retinal Pigment Epithelium - metabolism
rho-Associated Kinases - antagonists & inhibitors
ROCK inhibitor
Stem Cell Transplantation
transplantation
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Summary:Currently, retinal pigment epithelium (RPE) transplantation includes sheet and single-cell transplantation, the latter of which includes cell death and may be highly immunogenic, and there are some issues to be improved in single-cell transplantation. Y-27632 is an inhibitor of Rho-associated protein kinase (ROCK), the downstream kinase of Rho. We herein investigated the effect of Y-27632 in vitro on retinal pigment epithelium derived from induced pluripotent stem cells (iPS-RPE cells), and also its effects in vivo on the transplantation of iPS-RPE cell suspensions. As a result, the addition of Y-27632 in vitro showed suppression of apoptosis, promotion of cell adhesion, and higher proliferation and pigmentation of iPS-RPE cells. Y-27632 also increased the viability of the transplant without showing obvious retinal toxicity in human iPS-RPE transplantation into monkey subretinal space in vivo. Therefore, it is possible that ROCK inhibitors can improve the engraftment of iPS-RPE cell suspensions after transplantation.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22063237