# US 9,752,127 B2 · Composition for maintaining chromosomal stability of pluripotent stem cells, containing small-molecule compounds

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- Number: US 9,752,127 B2
- Document ID: US9752127B2
- Status: Granted
- Kind: B2
- Application number: 14/906,547
- Filed: 2014-07-22
- Published: 2016-06-09
- Granted: 2017-09-05
- Earliest claimed: 2013-07-27
- Assignees: Korea University Research and Business Foundation
- Applicants: Korea University Research and Business Foundation
- Inventors: Sunghoi Hong; Hang-Soo Park; In-Sik Hwang; Kyung-A Choi
- Web page: https://patentgrep.com/patent/US9752127B2

## CPC

- C12N 5/0696: {Artificially induced pluripotent stem cells, e.g. iPS}
- C12N 2500/38: Vitamins
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/602: Sox-2
- C12N 2501/603: Oct-3/4
- C12N 2501/604: Klf-4
- C12N 2501/606: c-Myc
- C12N 2501/727: Kinases (EC 2.7.)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention relates to a composition for maintaining the chromosomal stability of pluripotent stem cells, which contains a small-molecule compound, and more particularly, to a composition for maintaining the chromosomal stability of induced pluripotent stem cells, which contains a ROCK inhibitor, a MEK inhibitor, an ALK5 inhibitor or an antioxidant, which is capable of inhibiting chromosomal structural and numerical mutations or DNA damage during induction of induced pluripotent stem cell and the subsequent culture of the cells. The small-molecule compound-containing composition for maintaining the chromosomal stability of induced pluripotent stem cells increases the reprogramming rate and efficiency during production of induced pluripotent stem cells and exhibits excellent effects on the inhibition of chromosomal structural and numerical mutations or DNA damage. Thus, the composition of the present invention is very useful for the development of induced pluripotent stem cell therapeutic agents having excellent chromosomal stability.

## Claims

### Claim 1

A method for maintaining the chromosomal stability of induced pluripotent stem cells by inhibiting DNA damage, the method comprising:
treating the induced pluripotent stem cells with a composition consisting of SB431542, PD0325901, thiazovivin and L-ascorbic acid,
wherein the induced pluripotent stem cells are generated by introduction of genes consisting of Oct4, Klf4, Sox2, and cMyc.

### Claim 2 (depends on 1)

The method of claim 1, wherein the composition is added during induction of reprogramming.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition is added after induction of reprogramming.

### Claim 4

A method for culturing induced pluripotent stem cells, the method comprising:
culturing the induced pluripotent stem cells in a composition that contains, as an active ingredient, a small-molecule compound consisting of SB431542, PD0325901, thiazovivin and L-ascorbic acid,
wherein the induced pluripotent stem cells are generated by introduction of genes consisting of Oct4, Klf4, Sox2, and cMyc.

### Claim 5 (depends on 4)

The method of claim 4, further comprising culturing the induced pluripotent stem cells under a feeder cell-free condition.