Details

Autor(en) / Beteiligte

• Maruotti, Julien
• Sripathi, Srinivas R.
• Bharti, Kapil
• Fuller, John
• Wahlin, Karl J.
• Ranganathan, Vinod
• Sluch, Valentin M.
• Berlinicke, Cynthia A.
• Davis, Janine
• Kim, Catherine
• Zhao, Lijun
• Wan, Jun
• Qian, Jiang
• Corneo, Barbara
• Temple, Sally
• Dubey, Ramin
• Olenyuk, Bogdan Z.
• Bhutto, Imran
• Lutty, Gerard A.
• Zack, Donald J.

Titel

Small-molecule–directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-09, Vol.112 (35), p.10950-10955

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule–only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over onehalf of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE.