Use of Stem Cells to Reduce Leukocyte Extravasation

• US 20110020293A1
• Filed: 07/21/2010
• Published: 01/27/2011
• Est. Priority Date: 07/21/2009
• Status: Active Application

• Current Assignee: ABT Holding Company (Athersys, Inc.)
• Original Assignee: ABT Holding Company (Athersys, Inc.)
• Inventors: Van't Hof, Wouter, Woda, Juliana Megan
• Application Number:
  US12/840,722
• Publication Number:
  US 20110020293A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/42 Respiratory system, e.g. lungs, bronchi or lung cells
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2502/28 Vascular endothelial cells
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/5073 Stem cells
• CPC Class Codes: G01N 33/56966 Animal cells

Abstract

The invention is generally directed to reducing inflammation by means of cells that secrete factors that reduce leukocyte extravasation. Specifically, the invention is directed to methods using cells that secrete factors that downregulate the expression of cellular adhesion molecules in vascular endothelial cells. Downregulating expression of cellular adhesion molecules reduces leukocyte adhesion to the endothelial cells such that extravasation is reduced. The end result is a reduction of inflammation. The cells are non-embryonic non-germ cells that have pluripotent characteristics. These may include expression of pluripotential markers and broad differentiation potential.

Claims

1. A method of obtaining cells with a desired potency for one or more of the following:

(1) reduce leukocyte extravasation, (2) reduce leukocyte adhesion to vascular endothelium or to isolated endothelial cells, (3) reduce cytokine-mediated activation of endothelial cells, (4) reduce expression of one or more cell adhesion molecules on an endothelial cell, said method comprising assessing cells for and selecting cells with a desired potency for one or more of the effects of (1)-(4) above, the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.

2. A method to treat inflammation in a subject, the method comprising administering the selected cells of claim 1 to the subject in a therapeutically effective amount and for a time sufficient to achieve a therapeutic result.

3. A method to construct a cell bank, the method comprising expanding and storing the selected cells of claim 1 for future administration to a subject.

4. A method for drug discovery, the method comprising contacting the selected cells of claim 1 with an agent to assess the effect of the agent on the ability of the cells to effect any of events (1)-(4).

6. The method of claim 1 wherein the cytokine is selected from the group consisting of TNF-α

and IL-1.

7. The method of claim 1 wherein cytokine-mediated activation produces an increase in expression of one or more of E-selectin, P-selectin, VCAM-1, ICAM, and VCAM-2 in the endothelial cell.

8. The method of claim 1 wherein the cell adhesion molecule, the expression of which is reduced in the endothelial cell, is one or more of E-selectin, P-selectin, VCAM-1, ICAM, and VCAM-2.

5. A composition comprising cells assessed and selected for the desired potency to achieve one or more of the following:

1) reduce leukocyte extravasation, (2) reduce leukocyte adhesion to vascular endothelium or to isolated endothelial cells, (3) reduce cytokine-mediated activation of endothelial cells, (4) reduce expression of one or more cell adhesion molecules on an endothelial cell; and

the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.

9. A method to increase the potency of a cell to effect one of more of the following:

1) reduce leukocyte extravasation, (2) reduce leukocyte adhesion to vascular endothelium or to isolated endothelial cells, (3) reduce cytokine-mediated activation of endothelial cells, (4) reduce expression of one or more cell adhesion molecules on an endothelial cell;

the method comprising contacting cells with IFN-γ

, IL-1β

, and TNF-α

to produce cells that achieve one or more of effects (1)-(4);

the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.