Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells

TitleDerivation of functional retinal pigmented epithelium from induced pluripotent stem cells
Publication TypeJournal Article
Year of Publication2009
AuthorsBuchholz DE, Hikita ST, Rowland TJ, Friedrich AM, Hinman CR, Johnson LV, Clegg DO
JournalStem Cells
Volume27
Issue10
Pagination2427-34
Date Published2009 Oct
ISSN1549-4918
KeywordsBiomarkers, Brain Tissue Transplantation, Cell Differentiation, Cell Line, Cell Polarity, Cell Proliferation, Homeodomain Proteins, Humans, Integrin alphaV, Nerve Tissue Proteins, Octamer Transcription Factor-3, Phagocytosis, Phenotype, Pluripotent Stem Cells, Regeneration, Retinal Diseases, Retinal Pigment Epithelium, Retinal Rod Photoreceptor Cells, RNA, Messenger, SOXB1 Transcription Factors
Abstract

Human induced pluripotent stem cells (iPSCs) have great promise for cellular therapy, but it is unclear if they have the same potential as human embryonic stem cells (hESCs) to differentiate into specialized cell types. Ocular cells such as the retinal pigmented epithelium (RPE) are of particular interest because they could be used to treat degenerative eye diseases, including age-related macular degeneration and retinitis pigmentosa. We show here that iPSCs generated using Oct4, Sox2, Nanog, and Lin28 can spontaneously differentiate into RPE cells, which can then be isolated and cultured to form highly differentiated RPE monolayers. RPE derived from iPSCs (iPS-RPE) were analyzed with respect to gene expression, protein expression, and rod outer segment phagocytosis, and compared with cultured fetal human RPE (fRPE) and RPE derived from hESCs (hESC-RPE). iPS-RPE expression of marker mRNAs was quantitatively similar to that of fRPE and hESC-RPE, and marker proteins were appropriately expressed and localized in polarized monolayers. Levels of rod outer segment phagocytosis by iPS-RPE, fRPE, and hESC-RPE were likewise similar and dependent on integrin alpha v beta 5. This work shows that iPSCs can differentiate into functional RPE that are quantitatively similar to fRPE and hESC-RPE and further supports the finding that iPSCs are similar to hESCs in their differentiation potential.

DOI10.1002/stem.189
Alternate JournalStem Cells
PubMed ID19658190
Grant List1S10RR017753-07 / RR / NCRR NIH HHS / United States
5R24EY014799-05 / EY / NEI NIH HHS / United States