title: Generation of retinal pigmented epithelium from iPSCs derived from the conjunctiva of donors with and without age related macular degeneration.
abstract: Fidelity in pluripotent stem cell differentiation protocols is necessary for the therapeutic and commercial use of cells derived from embryonic and induced pluripotent stem cells. Recent advances in stem cell technology, especially the widespread availability of a range of chemically defined media, substrates and differentiation components, now allow the design and implementation of fully defined derivation and differentiation protocols intended for replication across multiple research and manufacturing locations. In this report we present an application of these criteria to the generation of retinal pigmented epithelium from iPSCs derived from the conjunctiva of donors with and without age related macular degeneration. Primary conjunctival cells from human donors aged 70-85 years were reprogrammed to derive multiple iPSC lines that were differentiated into functional RPE using a rapid and defined differentiation protocol. The combination of defined iPSC derivation and culture with a defined RPE differentiation protocol, reproducibly generated functional RPE from each donor without requiring protocol adjustments for each individual. This successful validation of a standardized, iPSC derivation and RPE differentiation process demonstrates a practical approach for applications requiring the cost-effective generation of RPE from multiple individuals such as drug testing, population studies or for therapies requiring patient-specific RPE derivations. In addition, conjunctival cells are identified as a practical source of somatic cells for deriving iPSCs from elderly individuals.
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Zhouhui
authors.initials: Z
authors.lastname: Geng
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Walsh
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Vincent
authors.initials: V
authors.lastname: Truong
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Hill
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Mara
authors.initials: M
authors.lastname: Ebeling
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Kapphahn
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Montezuma
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Ching
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Histology Core for Vision Research, University of Minnesota, Minneapolis, Minneapolis, Minnesota, United States of America.
authors.forename: Heidi
authors.initials: H
authors.lastname: Roehrich
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ferrington
authors.affiliation: Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: James R
authors.identifier: http://orcid.org/0000-0002-5074-2614
authors.initials: JR
authors.lastname: Dutton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D014019:Tissue Donors