Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration.
iScience
; 25(10): 105050, 2022 Oct 21.
Article
en En
| MEDLINE
| ID: mdl-36185374
ABSTRACT
The hostile microenvironment of the retina in patients with age-related macular degeneration (AMD) may trigger epithelial-to-mesenchymal transition (EMT) of grafted retinal pigment epithelial (RPE) cells, thus attenuating the therapeutic outcome. Here, we transformed human dedifferentiated induced pluripotent stem cell-derived RPE (iPSC-RPE) cells into induced RPE (iRPE) cells using a cocktail of four transcription factors (TFs)-CRX, MITF-A, NR2E1, and C-MYC. These critical TFs maintained the epithelial property of iRPE cells by regulating the expression of bmp7, forkhead box f2, lin7a, and pard6b, and conferred resistance to TGF-ß-induced EMT in iRPE cells by targeting ppm1a. The iRPE cells with Tet-on system-regulated c-myc expression exhibited EMT resistance and better therapeutic function compared with iPSC-RPE cells in rat AMD model. Our study demonstrates that endowing RPE cells with anti-EMT property avoids the risk of EMT after cells are grafted into the subretinal space, and it may provide a suitable candidate for AMD treatment.
Texto completo:
1
Bases de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
IScience
Año:
2022
Tipo del documento:
Article
País de afiliación:
China