Method for suppressing teratoma formation via selective cell death induction in undifferentiated human-induced pluripotent stem cells

Patent metadata

Field	Value
Publication number	US-2016002604-A1
Application number	US-201314434873-A
Country	US
Kind code	A1
Filing date	Oct 11, 2013
Priority date	Oct 12, 2012
Publication date	Jan 7, 2016
Grant date	—

Abstract

The present invention relates to a method for preparing differentiated cells derived from induced pluripotent stem cell, wherein undifferentiated induced pluripotent stem cells (iPS) are removed, the method comprising steps of: (a) preparing a cell sample including undifferentiated induced pluripotent stem cells and differentiated cells by differentiating induced pluripotent stem cells; and (b) causing selective apoptosis of the undifferentiated induced pluripotent stem cells by treating the resultant in step (a) with quercetin of Formula 1 below or with YM-155 of Formula 2 below.
According to the present invention, the present invention makes it possible to effectively selectively cause apoptosis only of undifferentiated induced pluripotent stem cells by causing induced pluripotent stem cells to differentiate into specific differentiated cells and then carrying out culturing in a differentiating culture medium comprising quercetin or YM-155, and, in the induced pluripotent stem cell differentiation method according to the present invention, only undifferentiated induced pluripotent stem cells that are a cause of teratoma formation are selectively caused to die, and thus differentiated differentiating cells are completely unaffected. In other words, the invention can be expected to ensure safety as the possibility of tumor formation during clinical use as a cell therapeutic agent is eliminated since the survival and functioning of the differentiated cells is maintained unchanged.

First claim

1 . A method for preparing differentiated cells derived from induced pluripotent stem cells (iPS), in which undifferentiated induced pluripotent stem cells are removed, comprising:
(a) preparing a cell sample including undifferentiated induced pluripotent stem cells and differentiated cells by differentiating the induced pluripotent stem cells; and (b) causing selective apoptosis of the undifferentiated induced pluripotent stem cells by treating the resultant in step (a) with quercetin of Formula 1 below or YM-155 of Formula 2 below:

2 . The method of claim 1 , wherein the induced pluripotent stem cells are derived from humans, cattle, horses, goats, sheep, dogs, cats, mice, rats, or birds.

3 . The method of claim 1 , wherein the concentrations of quercetin and YM-155 are in the range of 20 μM to 100 μM and 2.5 nM to 80 nM, respectively.

4 . A cell composition in which undifferentiated induced pluripotent stem cells are removed by the method of claim 1 .

5 . A composition for selective apoptosis of undifferentiated induced pluripotent stem cells, comprising quercetin of Formula 1 below or YM-155 of Formula 2 below:

Assignees

• Univ Sogang Ind Univ Coop Foun

Inventors

• Cha Hyuk Jin
• Kim Kwang Soo

Classifications

• C12N2502/1347

  Smooth muscle cells · CPC title

• C12N2500/76

  from plants · CPC title

• C07D311/30

  not hydrogenated in the hetero ring, e.g. flavones · CPC title

• C12N2506/45

  from artificially induced pluripotent stem cells · CPC title

• C07D311/22

  with oxygen or sulfur atoms directly attached in position 4 · CPC title