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

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

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.

MeSH terms

  • 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
  • Macaca fascicularis
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism
  • Stem Cell Transplantation*
  • rho-Associated Kinases / antagonists & inhibitors*

Substances

  • Amides
  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Protein Kinase Inhibitors
  • Pyridines
  • Y 27632
  • rho-Associated Kinases