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A ROCK Inhibitor Promotes Graft Survival during Transplantation of iPS-Cell-Derived Retinal Cells
Authors:Masaaki Ishida  Sunao Sugita  Kenichi Makabe  Shota Fujii  Yoko Futatsugi  Hiroyuki Kamao  Suguru Yamasaki  Noriko Sakai  Akiko Maeda  Michiko Mandai  Masayo Takahashi
Affiliation:1.RIKEN Center for Biosystems Dynamics Research, Laboratory for Retinal Regeneration, Kobe 650-0047, Japan; (M.I.); (K.M.); (S.F.); (Y.F.); (H.K.); (S.Y.); (N.S.); (A.M.); (M.M.); (M.T.);2.Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;3.Vison Care Inc, Kobe 650-0047, Japan;4.Department of Ophthalmology, Kawasaki Medical School, Okayama 701-0114, Japan;5.Regenerative and Cellular Medicine Kobe Center, Sumitomo Dainippon Pharma Co., Ltd., Kobe 650-0047, Japan
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.
Keywords:ROCK inhibitor   iPS cells   retinal pigment epithelium   transplantation
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