Small chemical compound which promotes induction of differentiation of stem cells into insulin-producing cells and method for inducing differentiation of stem cells into insulin-producing cells using said small chemical compound

Patent metadata

Field	Value
Publication number	US-9617517-B2
Application number	US-201214115618-A
Country	US
Kind code	B2
Filing date	May 1, 2012
Priority date	May 2, 2011
Publication date	Apr 11, 2017
Grant date	Apr 11, 2017

Abstract

A purpose of the present invention is to provide a small chemical compound which especially promotes induction of the differentiation of ES cells into insulin-producing cells. Another purpose of the present invention is to provide: a method for inducing the differentiation of ES cells into insulin-producing cells using the compound; and an agent for promoting induction of the differentiation into insulin-producing cells. Another purpose of the present invention is to provide the thus-induced insulin-producing cells. Provided are: an agent for promoting induction of the differentiation of stem cells derived from a mammal into insulin-producing cells, which contains a compound that is selected from the group consisting of dopamine metabolism inhibitors, serotonin metabolism inhibitors, acetylchotine, acetylcholine degrading enzyme inhibitors and acetylcholine receptor activators; and a method for inducing differentiation using the agent for promoting induction of differentiation.

First claim

The invention claimed is:

1. A method for differentiating mammal-derived stem cells into insulin-producing cells comprising culturing said stem cells in a culture medium comprising a compound which inhibits incorporation of a monoamine into a monoamine transporter 2 (VMAT2)-positive vesicle in an amount of from 0.15 μM to 40 μM to produce insulin-producing cells, wherein the compound is selected from the group consisting of tetrabenazine, and α-methyltyrosine.

2. The method according to claim 1 , wherein the compound is α-methyltyrosine.

3. The method according to claim 1 , wherein the compound is tetrabenazine.

4. The method according to claim 1 , wherein the medium further comprises a compound which increases intracellular cAMP concentration.

5. The method according to claim 1 , wherein the medium further comprises a compound selected from the group consisting of cAMP, cell permeable cAMP analogs, Gαs protein-coupled receptor agonists, and Gαi protein-coupled receptor antagonists.

6. The method according to claim 1 wherein the medium further comprises cAMP or a cell permeable cAMP analog.

7. The method according to claim 2 , wherein the medium further comprises cAMP or a cell permeable cAMP analog.

8. The method according to claim 3 , wherein the medium further comprises cAMP or a cell permeable cAMP analog.

9. The method according to claim 8 , wherein, the medium comprises tetrabenazine in an amount of from 0.15 μM to 10.0 μM and cAMP or a cell permeable cAMP analog in an amount from 0.15 μM to 5.0 μM.

10. The method according to claim 7 , wherein insulin-producing cells are glucose-responsive insulin-secreting cells.

11. The method according to claim 8 , wherein insulin producing cells are glucose-responsive insulin-secreting cells.

Assignees

• Kume Shoen
• Sakano Daisuke
• Shiraki Nobuaki
• Umeda Kahoko
• Yamazoe Taiji
• Kume Kazuhiko
• Uesugi Motonari
• Nat Univ Corp Kumamoto Univ
• Univ Kyoto

Inventors

• Kume Shoen
• Sakano Daisuke
• Shiraki Nobuaki
• Umeda Kahoko
• Yamazoe Taiji
• Kume Kazuhiko
• Uesugi Motonari

Classifications

• C12N2501/385

  of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR] · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/221

  with compounds having an amino group, e.g. acetylcholine, acetylcarnitine · CPC title

• A61K31/475

  having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine (vincamine A61K31/4375) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title