Chemical approaches for generation of induced pluripotent stem cells

Patent metadata

Field	Value
Publication number	US-9394524-B2
Application number	US-75338610-A
Country	US
Kind code	B2
Filing date	Apr 2, 2010
Priority date	Mar 17, 2008
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

The present invention provides for identification and use of small molecules to induce pluripotency in mammalian cells as well as other methods of inducing pluripotency.

First claim

What is claimed is:

1. A method of producing an induced pluripotent stem cell from a mammalian non-pluripotent cell, the method comprising
(a) introducing into the mammalian non-pluripotent cell, one or more expression cassettes comprising an Oct4 polynucleotide, a Sox2 polynucleotide, and a Klf4 polynucleotide, and
(b) contacting the cell of step (a) with a TGFβ receptor/ALK5 inhibitor and a GSK-3 inhibitor,
thereby producing an induced pluripotent stem cell from the mammalian non-pluripotent cell.

2. The method of claim 1 , further comprising contacting the cell with a second agent selected from the group consisting of a MEK inhibitor and an Erk inhibitor.

3. The method of claim 2 , wherein the second agent is a MEK inhibitor.

4. The method of claim 1 , further comprising contacting the mammalian non-pluripotent cell with a histone deacetylase (HDAC) inhibitor.

5. The method of claim 1 , wherein the TGFβ receptor/ALK5 inhibitor is selected from the group consisting of: A-83-01 and SB431542.

6. The method of claim 2 or claim 3 , wherein the MEK inhibitor is PD0325901.

7. The method of claim 1 , wherein the GSK-3 inhibitor is selected from the group consisting of: CHIR99021, CHIR98014, and 6-bromoindirubin-3′-oxime (BIO).

8. The method of claim 1 , wherein the one or more expression cassettes further comprises a c-Myc polynucleotide.

Assignees

• Lin Tongxiang
• Li Wenlin
• Ding Sheng
• Scripps Research Inst

Inventors

• Lin Tongxiang
• Li Wenlin
• Ding Sheng

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title