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Xiaodi Qiu, Tianjin Liu, Yi Lu; Efficient Generation of Lens Progenitor Cells from Cataract Patient-specific Induced Pluripotent Stem Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3048.
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© ARVO (1962-2015); The Authors (2016-present)
To establish a new model for the effects of aging on lens and lens development, we examined whether human lens epithelial cells (HLECs) can be induced into iPS cells. We further sought to establish whether these iPS cells could be differentiated into lens progenitor cells in defined chemical conditions.
hLECs were separated and cultured from a 56-yr-old cataract patient, after cell reprogramming factors (OCT-4,SOX-2,KLF-4) transformation, yielding induced pluripotent stem (iPS) cells with high reprogramming efficiencies. For lens specific differentiation, we applied 3-step induction procedure and analysis of 7 lens differentiation markers (PAX6, SOX2, SIX3, CRYAB, CRYAA,, BFSP1, and MIP) in iPS cells and ES cells from d 0 to 30.
HLEC-derived iPS (HLE-iPS) cell colonies were indistinguishable from human ES cells with regards to morphology, gene pattern, pluripotent marker expression, and their ability to generate all embryonic germ layers in vitro and in vivo. Further more, HLE-iPS can be differentiated into large quantities of lens progenitor-like cells with defined factors (Noggin BMP, FGF2), and these cells expressed and accumulated lens-specific markers. Lens specific iPS cells have higher differentiation efficiency than that of ES.
Our studies identify a high efficient procedure to generate lens cells from patient specific iPS derived from various cataract patients. These patient-derived pluripotent cells constitute a valuable model for the developmental and molecular biological mechanisms that underlie cell determination during lens development and cataract pathophysiology.
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