Modulation of splenocytes in cell therapy

• US 9,937,208 B2
• Filed: 06/01/2011
• Issued: 04/10/2018
• Est. Priority Date: 05/12/2010
• Status: Active Grant

• Current Assignee: ABT Holding Company (Athersys, Inc.), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: ABT Holding Company (Athersys, Inc.)
• Inventors: Mays, Robert W.
• Primary Examiner(s): Belyavskyi, Michail A
• Application Number:
  US13/150,491
• Publication Number:
  US 20110293642A1
• Time in Patent Office: 2,505 Days
• Field of Search: None
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem 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 37/04 Immunostimulants
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696
• CPC Class Codes: G01N 2333/5406 IL-4
• CPC Class Codes: G01N 2333/5412 IL-6
• CPC Class Codes: G01N 2333/5428 IL-10
• CPC Class Codes: G01N 2333/545 IL-1
• CPC Class Codes: G01N 2333/70514 CD4
• CPC Class Codes: G01N 2333/70517 CD8
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2800/24 Immunology or allergic disorders SLE G01N2800/104
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/5047 Cells of the immune system
• CPC Class Codes: G01N 33/505 involving T-cells
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that have one or more of the following effects in an injured subject: interact with splenocytes, preserve splenic mass, increase proliferation of CD4⁺ and CD8⁺ T-cells, increase IL-4 and IL-10, decrease IL-6 and IL-1β, and increase M2:M1 macrophage ratio at the site of injury. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to have these effects. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired potency for achieving these effects.

Claims

1. A method for obtaining cells that have the ability to (1) preserve splenic mass in an injury, (2) increase splenocyte proliferation in the spleen, (3) increase T-regulatory cells;

(4) increase one or more of IL-10 and IL-4, or (5) decrease IL-2 and IL-1β

, the method comprising assaying cells for said ability by performing one or more of;

(1) an assay of splenic mass in an injury, (2) an assay of splenocyte proliferation in the spleen, (3) an assay of T-regulatory cells (4) an assay of IL-10 and IL-4, and (5) an assay of IL-2 and IL-1β

, wherein said cells that are assayed are 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 the endodermal, ectodermal, and mesodermal germ layers.

2. The method of claim 1 wherein the cells express telomerase.

3. The method of claim 1 wherein the cells express oct4.

4. The method of claim 1 wherein the cells express oct4 and telomerase.

5. The method of claim 1 wherein the cells can differentiate into cell types of at least two of the endodermal, ectodermal, and mesodermal germ layers.

6. The method of claim 1 wherein the cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers.

7. The method of claim 1 wherein the cells express oct4 and telomerase and can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.

8. The method of claim 1 wherein the cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers and express telomerase and oct4.

9. The method of claim 1 wherein the cells are human.

10. The method of claim 1 wherein the cells are derived from bone marrow.