TY - JOUR
T1 - Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives
AU - Salero, Enrique
AU - Blenkinsop, Timothy A.
AU - Corneo, Barbara
AU - Harris, Ashley
AU - Rabin, David
AU - Stern, Jeffrey H.
AU - Temple, Sally
N1 - Funding Information:
This work was supported by NYSTEM DOH (grants C024399 to E.S. and C024414 to S.T.), American Health Assistance Foundation (M200037 to S.T.), the Steinbach Foundation, and the Regenerative Research Foundation. We acknowledge with deep gratitude the support and encouragement of Dr. Heinrich Medicus. We thank Soma De for early help in establishing the culture system, Meredithe Applebury and Michael Radosevich for helpful discussions, Sheldon Miller and Arvydas Maminishkis for fetal RPE cultures and invaluable insight, and Carol Charniga and Patricia Lederman for technical assistance. We are indebted to the eye donors and their families.
Funding Information:
Human eyes from 22- to 99-year-old donors were obtained from The Eye Bank for Sight Restoration, Inc. (New York, NY), the National Disease Research Interchange (NDRI) (Philadelphia, PA) (supported by NIH grant 5 U42 RR006042), and the Lions Eye Bank (Albany, NY). The eyes were cut at the ora serrata, the anterior segment was discarded, and the vitreous and retina were removed, exposing the RPE layer. RPE dissection and dissociation was performed as described previously ( Burke et al., 1996; Maminishkis et al., 2006 ). Gentle trituration within the eyecup using care to maintain Bruch's membrane yields a suspension of largely single RPE cells with minimal contamination by rod outer segments, blood, or other cell types.
PY - 2012/1/6
Y1 - 2012/1/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84855517118&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2011.11.018
DO - 10.1016/j.stem.2011.11.018
M3 - Article
C2 - 22226358
AN - SCOPUS:84855517118
SN - 1934-5909
VL - 10
SP - 88
EP - 95
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -