Abstract
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.
Highlights
A Rho-associated protein kinase (ROCK) Inhibitor Promotes Graft Survival duringMasaaki Ishida 1,2,† , Sunao Sugita 1,3, *,† , Kenichi Makabe 1 , Shota Fujii 1 , Yoko Futatsugi 1 , Hiroyuki Kamao 1,4 , Suguru Yamasaki 1,5 , Noriko Sakai 1,3 , Akiko Maeda 1 , Michiko Mandai 1 and Masayo Takahashi 1,3
Clinical trials using human embryonic stem cell/induced pluripotent stem cell (ESC/iPSC)-derived tissues have shown promise [1,2]
Since transplantation using a Rho-associated protein kinase (ROCK) inhibitor has been successful in clinical trials, in the present study we investigated the effect of Y-27632 on our established iPS-retinal pigment epithelium (RPE) culture and iPS-RPE cell transplantation system
Summary
Masaaki Ishida 1,2,† , Sunao Sugita 1,3, *,† , Kenichi Makabe 1 , Shota Fujii 1 , Yoko Futatsugi 1 , Hiroyuki Kamao 1,4 , Suguru Yamasaki 1,5 , Noriko Sakai 1,3 , Akiko Maeda 1 , Michiko Mandai 1 and Masayo Takahashi 1,3. Survival during Transplantation of iPS-Cell-Derived Retinal Cells. Regenerative and Cellular Medicine Kobe Center, Sumitomo Dainippon Pharma Co., Ltd., Kobe 650-0047, Japan
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