IMMUNOPHENOTYPE AND IMMUNOGENICITY OF HUMAN ADIPOSE DERIVED CELLS

• US 20110158959A1
• Filed: 11/29/2010
• Published: 06/30/2011
• Est. Priority Date: 07/15/2005
• Status: Abandoned Application

• Current Assignee: Cognate BioServices, Inc., Louisiana State University Agricultural & Mechanical College (Louisiana State University System)
• Original Assignee: Artecel Inc.
• Inventors: Mitchell, James B. II, McIntosh, Kevin R., Gimble, Jeffrey M.
• Application Number:
  US12/955,639
• Publication Number:
  US 20110158959A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

The present invention encompasses methods and compositions for generating an isolated adipose tissue-derived stromal cell exhibiting a low level of immunogenicity. The present invention encompasses methods and compositions for reducing an immune response associated with transplantation by administering the recipient with an amount of adipose tissue-derived stromal cells effective to reduce or inhibit host rejection and/or host versus graft disease.

Claims

1. An isolated adipose tissue-derived adult stromal (ADAS) cell exhibiting a non-immunogenic characteristic, wherein said cell has been passaged up to at least the second passage, further wherein said cell expresses a stem cell associated characteristic selected from the group consisting of human multidrug transporter (ABCG2) and aldehyde dehydrogenase (ALDH).

2. The cell of claim 1, wherein said cell has been passaged up to at least the sixteenth passage.

3. The cell of claim 1, wherein exogenous genetic material has been introduced into said cell.

4. The cell of claim 1, wherein said cell is derived from a human.

5. The cell of claim 1, wherein said cell is allogeneic to a recipient thereof.

6. The cell of claim 1, wherein said cell is xenogeneic to a recipient thereof.

7. A method of treating a transplant recipient to reduce in said recipient an immune response of effector cells against an alloantigen, the method comprising:

administering to a transplant recipient, an isolated adipose tissue-derived adult stromal (ADAS) cell exhibiting a non-immunogenic characteristic, wherein said ADAS cell has been passaged up to at least the second passage, further wherein said ADAS cell expresses a stem cell associated characteristic selected from the group consisting of human multidrug transporter (ABCG2) and aldehyde dehydrogenase (ALDH), in an amount effective to reduce an immune response of effector cells against an alloantigen, whereby in the transplant recipient said effector cells have a reduced immune response against said alloantigen.

8. The method of claim 7, wherein said effector cell is a T cell.

11. The method of claim 8, wherein said T cell is present in the transplant.

12. The method of claim 7, wherein said effector cell is a T cell activated prior to administration of said ADAS cell to a recipient, and further wherein said immune response is the reactivation of said T cell from the donor.

16. The method of claim 7, further comprising administering to said recipient an immunosuppressive agent.

9-10. -10. (canceled)

13-15. -15. (canceled)

17-23. -23. (canceled)

24. A method of reducing an immune response by an effector cell against an alloantigen, the method comprising:

contacting an effector cell with an isolated adipose tissue-derived adult stromal (ADAS) cell exhibiting a non-immunogenic characteristic, wherein said ADAS cell has been passaged up to at least the second passage, further wherein said cell ADAS expresses a stem cell associated characteristic selected from the group consisting of human multidrug transporter (ABCG2) and aldehyde dehydrogenase (ALDH), in an amount effective to reduce an immune response by said effector cell against said alloantigen.

25. The method of claim 24 wherein said effector cell is a T cell.

26. A method of isolating an adipose tissue-derived stromal (ADAS) cell from a population of cells derived from adipose tissue, the method comprising:

providing an antibody specific for ABCG2;

contacting said population of adipose-derived cells with said antibody under conditions suitable for formation of an antibody-adipose tissue-derived stromal cell complex; and

substantially separating said antibody-adipose tissue-derived stromal cell complex from said population of adipose-derived cells;

thereby isolating said adipose tissue-derived stromal cell.

27. The method of claim 26, wherein said antibody is conjugated to a physical support.

28. The method of claim 27, wherein said physical support is selected from the group consisting of a microbead, a magnetic bead, a panning surface, a dense particle for density centrifugation, an adsorption column and an adsorption membrane.

30. The method of claim 26, wherein said antibody-adipose tissue-derived stromal cell complex is substantially separated from said population of adipose-derived cells using a method selected from the group consisting of fluorescence activated cell sorting (FACS) and magnetic activated cell sorting (MACS).

29. (canceled)

31. A method of enriching adipose tissue-derived stromal cells from a population of adipose-derived cells, said method comprising:

providing an antibody specific for ABCG2;

contacting said population of adipose-derived cells with said antibody under conditions suitable for formation of an antibody-adipose tissue-derived stromal cell complex; and

substantially separating said antibody-adipose tissue-derived stromal cell complex from said population of adipose-derived cells;

thereby isolating said adipose tissue-derived stromal cell.

32. The method of claim 31, wherein said antibody is conjugated to a physical support.

33-35. -35. (canceled)

36. A method of identifying an adipose tissue-derived stromal (ADAS) cell positive for ALDH from a population of cells derived from adipose tissue, the method comprising:

providing a cleavable substrate specific for ALDH to said population of cells, wherein said substrate when so present in an ALDH+ cell is cleaved, further wherein said cleaved substrate emits a fluorescence thereby identifying an ALDH+ ADAS cell.