Compostition for reprogramming cells

• US 10,584,316 B2
• Filed: 05/10/2018
• Issued: 03/10/2020
• Est. Priority Date: 12/13/2008
• Status: Active Grant

• Current Assignee: Babak Esmaeli-Azad
• Original Assignee: Babak Esmaeli-Azad
• Inventors: Esmaeli-Azad, Babak
• Primary Examiner(s): Noble, Marcia S
• Application Number:
  US15/976,796
• Publication Number:
  US 20180258405A1
• Time in Patent Office: 670 Days
• CPC Class Codes: C12N 2501/02 Compounds of the arachidonic acid pathway, e.g. prostaglandins, leukotrienes
• CPC Class Codes: C12N 2501/065 Modulators of histone acetylation
• CPC Class Codes: C12N 2501/415 Wnt; Frizzeled
• CPC Class Codes: C12N 2503/00 Use of cells in diagnostics
• CPC Class Codes: C12N 2506/1307 from adult fibroblasts
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2539/00 Supports and/or coatings for cell culture characterised by properties
• CPC Class Codes: C12N 5/0696 Artificially induced pluripotent stem cells, e.g. iPS
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 33/5073 Stem cells

Abstract

Described here are three-dimensional microenvironment niches prepared from biomaterial compositions that support growth and self renewal of stem cells. The invention also provides methods for inducing pluripotency in a somatic cell using chemical compounds, as well as methods for screening for compounds that can induce pluripotency in a somatic cell.

Claims

1. A composition for reprogramming at least one somatic cell to a pluripotent stem cell, the composition comprising:

a polymer hydrogel that further comprises a polyether cross linker;

valproic acid; and

at least one reprogramming agent, wherein the at least one reprogramming agent is a signal transduction pathway modulator.

2. The composition of claim 1, wherein the polyether cross linker is polyethylene glycol diacrylate.

3. A composition is for reprogramming at least one somatic cell to a pluripotent stem cell, the composition comprising:

a polymer hydrogel;

valproic acid; and

at least one reprogramming agent, wherein the at least one reprogramming agent is thiol-modified hyaluronan.

4. A composition for reprogramming at least one somatic cell to a pluripotent stem cell, the composition comprising:

a polymer hydrogel;

valproic acid; and

at least one reprogramming agent, wherein the at least one reprogramming agent is chosen from the group consisting of 6-bromoindirubin-3′

-oxime (BIO);

indirubin-5-nitro-3′

-oxime (INO);

2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-napthyridine;

1-4(-Methylphenyl)-2-(4,5,6,7-tetrahydro-2-imino-3(2H)-benzothiazolyl) ethanone HBr (Pifithrin-α

);

prostaglandin J2; and

prostaglandin E2.

5. A composition for reprogramming cells, the composition comprising:

a polymer hydrogel;

valproic acid; and

at least one signal transduction pathway modulator chosen from the group consisting of Wnt, Hedgehog, cyclooxygenase, p53, NF-κ

B, PKC, PGE-2 and combinations thereof.

6. The composition of claim 5, wherein the composition is capable of reprogramming at least one somatic cell to pluripotency resulting in at least one pluripotent cell.

7. The composition of claim 6, wherein the at least one pluripotent cell is a somatic stem cell.

8. The composition of claim 5, further comprising at least one growth factor.

9. The composition of claim 8, wherein the at least one growth factor is selected from the group consisting of epidermal growth factor;

fibroblast growth factor;

Noggin;

BDNF;

NGF;

Insulin;

IGF-1;

IGF-2; and

PDGF.

10. The composition of claim 5, wherein at least one signal transduction pathway further comprises at least one component selected from the group consisting of 6-bromoindirubin-3′

-oxime (BIO);

indirubin-5-nitro-3′

-oxime (INO);

2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-napthyridine;

1-4(-Methylphenyl)-2-(4,5,6,7-tetrahydro-2-imino-3(2H)-benzothiazolyl) ethanone HBr (Pifithrin-α

);

prostaglandin J2; and

prostaglandin E2.