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

• 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
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22063237

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.