4.7 Article

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

期刊

出版社

MDPI
DOI: 10.3390/ijms22063237

关键词

ROCK inhibitor; iPS cells; retinal pigment epithelium; transplantation

资金

  1. AMED [JP18bm0204002, JP17bk0104002]
  2. KAKENHI [18H02959]
  3. Grants-in-Aid for Scientific Research [18H02959] Funding Source: KAKEN

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Research has shown that the addition of Y-27632 in vitro can suppress apoptosis, promote cell adhesion and proliferation, and increase the survival rate of transplants. In vivo experiments with human iPS-RPE cell transplantation into monkey eyes showed no obvious retinal toxicity caused by Y-27632.
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.

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