Generation of hESC-derived retinal pigment epithelium on biopolymer coated polyimide membranes.
The in vitro generation of a functional retinal pigment epithelium (RPE) for therapeutic applications requires a limitless source of RPE cells and a supporting scaffold, which improves cell survival and promotes the acquisition of the RPE phenotype. We successfully differentiated human embryonic stem cells (hESCs) toward RPE on a transplantable, biopolymer coated polyimide (PI) membrane. We studied various membrane coatings of which several lead to the generation of a tight and highly polarized epithelium having typical characteristics and functions of human RPE. The cells established a distinctive hexagonal, cobblestone morphology with strong pigmentation, expressed RPE specific genes and proteins, and phagocytosed photoreceptor outer segments (POS) after co-culture with rat retinal explants. The barrier function of hESC-derived RPE (hESC-RPE) monolayers was confirmed by transepithelial electrical resistance and permeability measurements. In conclusion, we show that the PI biomembrane is a suitable scaffold for hESC-RPE tissue engineering.
Centre for Drug Research, Faculty of Pharmacy, Viikinkaari 5E, 00014 University of Helsinki, Helsinki, Finland.
Astrid
A
Subrizi
Hanna
H
Hiidenmaa
Tanja
T
Ilmarinen
Soile
S
Nymark
Peter
P
Dubruel
Hannu
H
Uusitalo
Marjo
M
Yliperttula
Arto
A
Urtti
Heli
H
Skottman
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007094:Imides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
D020099:Coated Materials, Biocompatible; D007094:Imides; D011108:Polymers