Induction of pluripotent cells
First Claim
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1. A composition comprising:
- an activin receptor-like kinase 5 (ALK5) inhibitor;
a MAP/ERK kinase (MEK) inhibitor; and
a Rho kinase (ROCK) inhibitor, wherein the ROCK inhibitor has the structure;
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Abstract
The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (>200 fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, non-viral methods for reprogramming human somatic cells.
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Citations
24 Claims
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1. A composition comprising:
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an activin receptor-like kinase 5 (ALK5) inhibitor; a MAP/ERK kinase (MEK) inhibitor; and a Rho kinase (ROCK) inhibitor, wherein the ROCK inhibitor has the structure; - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A mixture comprising:
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one or more mammalian cells; an ALK5 inhibitor; a MEK inhibitor; and a ROCK inhibitor, wherein the ROCK inhibitor has the structure; - View Dependent Claims (11, 12, 13, 19, 20, 21)
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14. A method of inducing non-pluripotent mammalian cells into induced pluripotent mammalian stem cells, comprising:
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(a) introducing Oct-3/4, Klf4, Sox2, and optionally c-Myc into the non-pluripotent cells; and (b) contacting the non-pluripotent cells with an ALK5 inhibitor, a MEK inhibitor, and a ROCK inhibitor, wherein the ROCK inhibitor has the structure; - View Dependent Claims (15, 16, 17, 18, 22, 23, 24)
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Specification