Using undifferentiated embryonic stem cells to control the immune system

• US 7,799,324 B2
• Filed: 09/24/2004
• Issued: 09/21/2010
• Est. Priority Date: 12/07/2001
• Status: Expired due to Fees

• Current Assignee: Asterias Biotherapeutics Incorporated (Lineage Cell Therapeutics, Inc.), University of Western Ontario
• Original Assignee: Geron Corporation, University of Western Ontario
• Inventors: Majumdar, Anish Sen, Madrenas, Joaquin, Ferber, Iris A., Bhatia, Mickie
• Primary Examiner(s): Paras, Jr.; Peter
• Assistant Examiner(s): MONTANARI, DAVID A
• Application Number:
  US10/949,702
• Publication Number:
  US 20050282272A1
• Time in Patent Office: 2,188 Days
• Field of Search: 424/93.1, 435/325
• US Class Current: 424/93.21
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 41/0023 Agression treatment or altering
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 2501/125 Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/155 Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 2501/22 Colony stimulating factors (G-CSF, GM-CSF)
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/41 Hedgehog proteins; Cyclopamine (inhibitor)
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 5/0634 Cells from the blood or the immune system

Abstract

This disclosure provides a system for minimizing the alloreactivity of tissue transplants. The patient is administered with undifferentiated embryonic stem cells or early progenitor cells. This induces a state of inflammatory quiescence or immune unresponsiveness, which in turn enhances engraftment of cells derived from the same stem cell line given for purposes of regenerative medicine.

Claims

1. A method of inducing a reduced lymphocyte proliferative response to a MHC type presented on an hES cell in a subject, comprising administering to the subject a cell population comprising inactivated undifferentiated hES cells or inactivated embryoid body cells obtained therefrom, thereby obtaining a reduced lymphocyte proliferative response to said MHC type presented on said hES cells than if said cell population had not been administered.

2. The method of claim 1, wherein the cell population has been inactivated by irradiation, treatment with mitomycin c, or fixation with paraformaldehyde.

3. A method of reducing leukocyte infiltration in situ, comprising administering at or around the site of inflammation, a cell population comprising inactivated undifferentiated hES cells or inactivated embryoid body cells obtained therefrom.

4. The method of claim 3, comprising administering at or around the site of inflammation, inactivated undifferentiated hES cells.

5. The method of claim 3, comprising administering at or around the site of inflammation, inactivated embryoid body cells.

6. The method of claim 3, wherein the cell population has been inactivated by irradiation, treatment with mitomycin c, or fixation with paraformaldehyde.

7. A method for inducing a reduced lymphocyte proliferative response to a MHC type presented on an hES cell in a subject, comprising:

a) administering to the subject a first cell population comprising inactivated undifferentiated hES cells or inactivated embryoid body cells obtained therefrom; and

b) administering to the subject a second cell population differentiated from the same line of hES cells;

wherein the subject has a reduced lymphocyte proliferative response to said second cell population compared to a subject that has only been administered the cell population of b.

8. The method of claim 7, wherein the first cell population comprises inactivated undifferentiated hES cells.

9. The method of claim 7, wherein the first cell population comprises inactivated embryoid body cells.

10. The method of claim 7, wherein the first cell population has been inactivated by irradiation, treatment with mitomycin c, or fixation with paraformaldehyde.

11. The method of claim 7, wherein the second cell population is a population of hepatocytes, neurons, oligodendrocytes, cardiomyocytes, osteogenic cells, mesenchymal cells, hematopoietic cells, islet cells, or chondrocytes.