Stem Cell Cultures

Patent metadata

Field	Value
Publication number	US-2016304833-A1
Application number	US-201615098546-A
Country	US
Kind code	A1
Filing date	Apr 14, 2016
Priority date	Dec 3, 2008
Publication date	Oct 20, 2016
Grant date	—

Abstract

The present invention relates compounds for stabilizing cells and methods of their use.

First claim

What is claimed is:

1 . A method for enhancing cell survival and proliferation, the method comprising:
(a) generating isolated cells comprising stem cells, progenitor cells, or differentiated cells therefrom; and (b) contacting the isolated cells with an amount of a compound having formula (I) sufficient to improve survival of the cells by at least 2-fold compared to the absence of the compound:

wherein,
L 2 is substituted or unsubstituted C 1 -C 10 alkylene; and
y is an integer from 0 to 3;
z is an integer from 0 to 5;
X is —N═, —CH═ or —CR 5 ═;
R 1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 , R 4 and R 5 are independently —CN, —S(O) n R 6 , —NR 7 R 8 , —C(O)R 9 , —NR 10 —C(O)R 11 , —NR—C(O)—OR 13 , —C(O)NR 14 R 15 , —NR 16 S(O) 2 R 17 , —OR 18 , —S(O) 2 N(R 19 ) 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein n is an integer from 0 to 2, wherein if z is greater than 1, two R 3 moieties are optionally joined together to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and
R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 19 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
or a racemate, diastereomer, tautomer, or a geometric isomer thereof, or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein the isolated cells are
(a) in adherent cultures; (b) in suspension cultures; (c) single dissociated cells; or (d) aggregated cells.

3 . The method of claim 1 , wherein the contacting step further comprising:
passaging the cells in cultures comprising the compound having formula (I) for at least 5, 10, 15, or 20, or more generations.

4 . The method of claim 1 or 3 , wherein the isolated cells:
(a) are homogenous;
(b) have morphology of hESCs;
(c) express pluripotency markers;
(d) maintain normal karyotype;
(e) are capable of self-renewal;
(f) are protected from cell death;
(g) are capable of forming teratomas;
(h) are capable of differentiating into three primary germ layers;
(i) are capable of lineage-specific differentiation;
(j) are capable of forming embryoid bodies after single cell dissociation; and/or
(k) have increased cell adhesion ability after single cell dissociation.

5 . The method of claim 1 , wherein the contacting step further comprising:
(a) modulating cell surface level of E-cadherins comprising (i) stabilizing E-cadherin on cell surface; and/or (ii) inhibiting endocytosis of E-cadherins; or (b) modulating integrin activity comprising (i) increasing integrin expression; and/or (ii) converting integrin into an active conformation.

Assignees

• Scripps Research Inst

Inventors

• Xu Yue
• 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

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title