A new efficient protocol for directed differentiation of retinal pigmented epithelial cells from normal and retinal disease induced pluripotent stem cells

Azadeh Zahabi, Ebrahim Shahbazi, Hamid Ahmadieh, Seyedeh Nafiseh Hassani, Mehdi Totonchi, Adeleh Taei, Najmehsadat Masoudi, Marzieh Ebrahimi, Nasser Aghdami, Ali Seifinejad, Faramarz Mehrnejad, Narsis Daftarian, Ghasem Hosseini Salekdeh, Hossein Baharvand*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

We describe a new, efficient protocol that involves the serial addition of noggin, basic fibroblast growth factor (bFGF), retinoic acid, and sonic hedgehog (Shh) for the differentiation of human induced pluripotent stem cells (hiPSC) to retinal pigmented epithelium (RPE) in a serum-and feeder-free adherent condition. hiPSC-RPE cells exhibited RPE morphology and specific molecular markers. Additionally, several hiPSC lines were generated from retinal-specific patients with Leber's congenital amaurosis, Usher syndrome, two patients with retinitis pigmentosa, and a patient with Leber's hereditary optic neuropathy. The RPE cells generated from these disease-specific hiPSCs expressed specific markers by the same RPE lineage-directed differentiation protocol. These findings indicate a new short-term, simple, and efficient protocol for differentiation of hiPSCs to RPE cells. Such specific retinal disease-specific hiPSCs offer an unprecedented opportunity to recapitulate normal and pathologic formation of human retinal cells in vitro, thereby enabling pharmaceutical screening, and potentially autologous cell replacement therapies for retinal diseases.

Original languageEnglish
Pages (from-to)2262-2272
Number of pages11
JournalStem Cells and Development
Volume21
Issue number12
DOIs
Publication statusPublished - 10 Aug 2012
Externally publishedYes

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