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一种 ROCK 抑制剂可促进 iPS 细胞衍生的视网膜细胞移植后的移植物存活。

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

机构信息

RIKEN Center for Biosystems Dynamics Research, Laboratory for Retinal Regeneration, Kobe 650-0047, Japan.

Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

出版信息

Int J Mol Sci. 2021 Mar 22;22(6):3237. doi: 10.3390/ijms22063237.

DOI:10.3390/ijms22063237
PMID:33810153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8004718/
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.

摘要

目前，视网膜色素上皮 (RPE) 移植包括片层和单细胞移植，后者包括细胞死亡，并且可能具有高度免疫原性，单细胞移植中仍存在一些需要改进的问题。Y-27632 是 Rho 相关蛋白激酶 (ROCK) 的抑制剂，ROCK 是 Rho 的下游激酶。本研究旨在探讨 Y-27632 在体外对诱导多能干细胞 (iPS-RPE 细胞) 衍生的视网膜色素上皮细胞的作用，以及其在体内对 iPS-RPE 细胞悬液移植的影响。结果表明，体外添加 Y-27632 可抑制细胞凋亡、促进细胞黏附，提高 iPS-RPE 细胞的增殖和色素沉着。Y-27632 还增加了移植细胞的活力，而在体内将人 iPS-RPE 移植到猴视网膜下腔中并未显示明显的视网膜毒性。因此， ROCK 抑制剂有可能改善 iPS-RPE 细胞悬液移植后的植入效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/345f/8004718/52aec8421cb1/ijms-22-03237-g007.jpg
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