title: A new efficient protocol for directed differentiation of retinal pigmented epithelial cells from normal and retinal disease induced pluripotent stem cells.
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.
authors.affiliation: Department of Stem Cells and Developmental Biology, The Academic Center for Education, Culture and Research-ACECR, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Zahabi
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Shahbazi
authors.forename: Hamid
authors.initials: H
authors.lastname: Ahmadieh
authors.forename: Seyedeh-Nafiseh
authors.initials: SN
authors.lastname: Hassani
authors.forename: Mehdi
authors.initials: M
authors.lastname: Totonchi
authors.forename: Adeleh
authors.initials: A
authors.lastname: Taei
authors.forename: Najmehsadat
authors.initials: N
authors.lastname: Masoudi
authors.forename: Marzieh
authors.initials: M
authors.lastname: Ebrahimi
authors.forename: Nasser
authors.initials: N
authors.lastname: Aghdami
authors.forename: Ali
authors.initials: A
authors.lastname: Seifinejad
authors.forename: Faramarz
authors.initials: F
authors.lastname: Mehrnejad
authors.forename: Narsis
authors.initials: N
authors.lastname: Daftarian
authors.forename: Ghasem Hosseini
authors.initials: GH
authors.lastname: Salekdeh
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000293:Adolescent; D000328:Adult; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D012164:Retinal Diseases / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology*
chemical_list: D000943:Antigens, Differentiation