Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives.
The retinal pigment epithelium (RPE) is a monolayer of cells underlying and supporting the neural retina. It begins as a plastic tissue, capable, in some species, of generating lens and retina, but differentiates early in development and remains normally nonproliferative throughout life. Here we show that a subpopulation of adult human RPE cells can be activated in vitro to a self-renewing cell, the retinal pigment epithelial stem cell (RPESC) that loses RPE markers, proliferates extensively, and can redifferentiate into stable cobblestone RPE monolayers. Clonal studies demonstrate that RPESCs are multipotent and in defined conditions can generate both neural and mesenchymal progeny. This plasticity may explain human pathologies in which mesenchymal fates are seen in the eye, for example in proliferative vitroretinopathy (PVR) and phthisis bulbi. This study establishes the RPESC as an accessible, human CNS-derived multipotent stem cell, useful for the study of fate choice, replacement therapy, and disease modeling.
Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
Enrique
E
Salero
Timothy A
TA
Blenkinsop
Barbara
B
Corneo
Ashley
A
Harris
David
D
Rabin
Jeffrey H
JH
Stern
Sally
S
Temple
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism