A New Efficient Protocol for Directed Differentiation of Retinal Pigmented Epithelial Cells from Normal and Retinal Disease Induced Pluripotent Stem Cells

被引:53
作者
Zahabi, Azadeh [1 ,5 ]
Shahbazi, Ebrahim [1 ]
Ahmadieh, Hamid [6 ]
Hassani, Seyedeh-Nafiseh [1 ]
Totonchi, Mehdi [1 ,2 ]
Taei, Adeleh [1 ]
Masoudi, Najmehsadat [2 ]
Ebrahimi, Marzieh [1 ]
Aghdami, Nasser [1 ]
Seifinejad, Ali [1 ]
Mehrnejad, Faramarz [5 ]
Daftarian, Narsis [6 ]
Salekdeh, Ghasem Hosseini [3 ]
Baharvand, Hossein [1 ,4 ]
机构
[1] ACECR, Dept Stem Cells & Dev Biol, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran, Iran
[2] ACECR, Dept Mol Syst Biol, Cell Sci Res Ctr, Royan Inst Stem Cell Biol & Technol, Tehran, Iran
[3] ACECR, Dept Genet, Reprod Biomed Res Ctr, Royan Inst Reprod Biomed, Tehran, Iran
[4] Univ Sci & Culture, Dept Dev Biol, ACECR, Tehran, Iran
[5] Azarbayjan Tarbiat Moallem Univ, Dept Biol, Tabriz, Iran
[6] Shahid Beheshti Univ Med Sci, Ophthalm Res Ctr, Tehran, Iran
关键词
IN-VITRO DIFFERENTIATION; VISUAL FUNCTION; IPS CELLS; HUMAN ES; GENERATION; MOUSE; INDUCTION; CULTURE; RPE; EYE;
D O I
10.1089/scd.2011.0599
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:2262 / 2272
页数:11
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