期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 35, 页码 10950-10955出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1422818112
关键词
retinal pigment epithelium; pluripotent stem cells; high-throughput screening; differentiation; age-related macular degeneration
资金
- Foundation Fighting Blindness Wynn-Gund Translational Acceleration Program
- Bright Focus Macular Degeneration Research Program
- NIH [5R21EY023812-02, P30EY001765]
- Research to Prevent Blindness, Inc.
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 one-half 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.
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