Agents and methods for inhibiting human pluripotent stem cell growth

Patent metadata

Field	Value
Publication number	US-9365830-B2
Application number	US-201013992931-A
Country	US
Kind code	B2
Filing date	Dec 8, 2010
Priority date	Dec 8, 2010
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

Abstract

The present invention relates to compositions and methods for inhibiting or suppressing undifferentiated or pluripotent stem cell growth and proliferation in a differentiated or differentiating cell population or culture.

First claim

What is claimed is:

1. An in vitro composition comprising a combination of:
a) at least one human pluripotent stem cell wherein the pluripotent stem cell has the ability to differentiate into cells of all three germ layers;
b) at least one differentiating or differentiated derivative from the human pluripotent stem cell; and
c) an effective amount of a pluripotent stem cell-selective inhibitor or cytotoxic agent selected from the group consisting of: caffeic acid, ivermectin, chelerythrine chloride and mixtures thereof, wherein the effective amount inhibits pluripotent cell growth in the composition as compared to pluripotent cell growth in a composition that does not comprise the effective amount of the inhibitor or cytotoxic agent.

2. The composition of claim 1 , wherein the human pluripotent stem cell is a human ES cells or a human iPS cell.

3. The composition of claim 1 , wherein effective amount has no effect on the proliferation or viability of the differentiating or differentiated cells.

4. The composition of claim 1 , wherein the effective amount does not inhibit the differentiation or differentiation potential of the differentiating or differentiated cells in the population.

5. The composition of claim 1 , wherein effective amount is selected from the group consisting of at least about 1 μM caffeic acid, at least about 1 μM ivermectin or at least about 5 μM chelerythrine chloride.

6. The composition of claim 1 , wherein the differentiating derivative or differentiated derivative comprises at least one cell type selected from: definitive endoderm cells, PDX1-negative foregut endoderm cells, PDX1-positive foregut endoderm cells, PDX1-positive pancreatic endoderm cells, endocrine progenitor cells and endocrine precursor cells.

7. An in vitro composition comprising a combination of:
a) at least one human pluripotent stem cell wherein the pluripotent cell has the ability to differentiate into cells of all three germ layers;
b) at least one differentiating or differentiated derivative from the human pluripotent stem cell; and
c) an effective amount of ivermectin, wherein the effective amount of ivermectin inhibits pluripotent cell growth in the composition as compared to pluripotent cell growth in a composition that does not comprise the effective amount of the inhibitor or cytotoxic agent.

8. The composition of claim 7 , wherein the human pluripotent stem cell is a human ES cells or a human iPS cell.

9. The composition of claim 7 , wherein the-effective amount of ivermectin has no effect on the proliferation or viability of the differentiating or differentiated cells.

10. The composition of claim 7 , wherein the effective amount of ivermectin does not inhibit the differentiation or differentiation potential of the differentiating or differentiated cells in the population.

11. The composition of claim 7 , wherein the effective amount of ivermectin is at least about 1 μM Ivermectin.

12. The composition of claim 7 , wherein the differentiating derivative or differentiated derivative comprises at least one cell type selected from: definitive endoderm cells, PDX1-negative foregut endoderm cells, PDX1-positive foregut endoderm cells, PDX1-positive pancreatic endoderm cells, endocrine progenitor cells and endocrine precursor cells.

13. A method for inhibiting human pluripotent cell growth in a population of cells, comprising:
preparing the in vitro composition of claim 1 , thereby inhibiting human pluripotent cell growth in the population of cells.

14. The method of claim 13 , wherein the human pluripotent stem cell is a human ES cell or a human iPS cell.

15. The method of claim 13 , wherein the effective amount comprises at least about 1 μM caffeic acid, at least about 1 μM ivermectin or at least about 5 μM chelerythrine chloride.

16. The method of claim 13 , wherein the effective amount has no effect on the viability or proliferation of the differentiating or differentiated cells.

17. The method of claim 13 , wherein the effective amount does not inhibit the differentiation or differentiation potential of the differentiating or differentiated cells.

18. The method of claim 13 , wherein the at least one differentiating or differentiated derivative comprises at least one cell type selected from: definitive endoderm cells, PDX1-negative foregut endoderm cells, PDX1-positive foregut endoderm cells, PDX1-positive pancreatic endoderm cells, endocrine progenitor cells and endocrine precursor cells.

19. The method of claim 13 , further comprising confirming a reduction in the number or percentage of human pluripotent stem cells in the population of cells.

Assignees

• Schulz Thomas
• Robins Allan
• Viacyte Inc

Inventors

• Schulz Thomas
• Robins Allan

Classifications

• C12N5/0696 Primary

  Artificially induced pluripotent stem cells, e.g. iPS · CPC title

• C12N5/0606 Primary

  Pluripotent embryonic cells, e.g. embryonic stem cells [ES] (embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696) · CPC title

• G01N33/5073

  Stem cells · CPC title

• C12N2501/999

  Small molecules not provided for elsewhere · CPC title

• C12N2503/02

  Drug screening · CPC title