Immunomodulatory properties of multipotent adult progenitor cells and uses thereof

• US 9,808,485 B2
• Filed: 01/06/2012
• Issued: 11/07/2017
• Est. Priority Date: 08/05/1999
• Status: Expired due to Term

• Current Assignee: ABT Holding Company (Athersys, Inc.)
• Original Assignee: Athersys, Inc., Oregon Health & Science University
• Inventors: Maziarz, Richard, Kovacsovics, Magdalena, Streeter, Philip, Deans, Robert, Van't Hof, Wouter
• Primary Examiner(s): Kim, Taeyoon
• Application Number:
  US13/345,036
• Publication Number:
  US 20120135043A1
• Time in Patent Office: 2,132 Days
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• 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 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• 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 7/06 Antianaemics
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

Isolated cells are described that are not embryonic stem cells, not embryonic germ cells, and not germ cells. The cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal lineages. The cells do not provoke a harmful immune response. The cells can modulate immune responses. As an example, the cells can suppress an immune response in a host engendered by allogeneic cells, tissues, and organs. Methods are described for using the cells, by themselves or adjunctively, to treat subjects. For instance, the cells can be used adjunctively for immunosuppression in transplant therapy. Methods for obtaining the cells and compositions for using them also are described.

Claims

1. A method of treatment of diabetes in a subject, comprising:

administering to a subject in need of treatment for diabetes—

by an effective route and in an effective amount to treat diabetes, cells that;

are not embryonic stem cells, embryonic germ cells, or germ cells;

can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages;

express telomerase;

are allogeneic or xenogeneic to the subject;

do not provoke a deleterious immune response in the subject; and

are effective to treat diabetes in the subject,—

wherein the cells are administered adjunctively to one or more other treatments, without also administering an immunosuppressive treatment adjunctively to treatment with the cells wherein the cells have not been genetically engineered to improve their immunomodulatory properties.

2. A method according to claim 1, wherein said cells can differentiate into at least one cell type of each of the endodermal, ectodermal, and mesodermal embryonic lineages.

3. A method according to claim 1, wherein said cells are positive for oct-3/4.

4. A method according to claim 1, wherein said cells have undergone at least 10 to 40 cell doublings in culture prior to their administration to the subject.

5. A method according to claim 1, wherein said cells are allogeneic to the subject.

6. A method according to claim 1, wherein said cells are administered to the subject adjunctively to another treatment that is administered before, at the same time as, or after said cells are administered.

7. A method according to claim 1, wherein said cells are mammalian cells.

8. A method according to claim 7, wherein said cells are human cells.

9. A method according to claim 7, wherein said cells are derived from cells isolated from placental tissue, umbilical cord tissue, umbilical cord blood, bone marrow, blood, spleen tissue, thymus tissue, spinal cord tissue, or liver tissue.

10. A method according to claim 1, wherein the subject is a mammal.

11. A method according to claim 10, wherein the subject is human.

12. A method according to claim 11, wherein said cells are administered to the subject in one or more doses comprising 10⁴ to 10⁸ of said cells per kilogram of the subject'"'"'s mass.

13. A method according to claim 1, wherein the diabetes is Type I diabetes mellitus.

14. A method according to claim 13, wherein said cells can differentiate into at least one cell type of each of the endodermal, ectodermal, and mesodermal embryonic lineages.

15. A method according to claim 13, wherein said cells are positive for oct-3/4.

16. A method according to claim 13, wherein said cells have undergone at least 10 to 40 cell doublings in culture prior to their administration to the subject.

17. A method according to claim 13, wherein said cells are allogeneic to the subject.

18. A method according to claim 13, wherein said cells are mammalian cells.

19. A method according to claim 13, wherein said cells are human cells.

20. A method according to claim 13, wherein said cells are derived from cells isolated from placental tissue, umbilical cord tissue, umbilical cord blood, bone marrow, blood, spleen tissue, thymus tissue, spinal cord tissue, or liver tissue.

21. A method according to claim 13, wherein the subject is a mammal.

22. A method according to claim 13, wherein the subject is human.

23. A method according to claim 13, wherein said cells are administered to the subject in one or more doses comprising 10⁴ to 10⁸ of said cells per kilogram of the subject'"'"'s mass.

24. A method according to claim 13, wherein the diabetes is Type I diabetes mellitus.

25. A method according to claim 1, wherein the cells are derived from bone marrow.

26. A method according to claim 25, wherein the cells are derived from human bone marrow.

27. A method according to claim 13, wherein the cells are derived from bone marrow.

28. A method according to claim 27, wherein the cells are derived from human bone marrow.