Immunomodulatory properties of multipotent adult progenitor cells and uses thereof

• US 20060263337A1
• Filed: 11/09/2005
• Published: 11/23/2006
• Est. Priority Date: 08/05/1999
• Status: Active Grant

• Current Assignee: ABT Holding Company (Athersys, Inc.), Oregon Health & Science University
• Original Assignee: ABT Holding Company (Athersys, Inc.)
• Inventors: Van't Hof, Wouter, Deans, Robert, Streeter, Philip, Maziarz, Richard, Kovacsovics, Magdalena
• Granted Patent: US 8,147,824 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• 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 adjunctive treatment of a subject, comprising:

administering to a subject at risk for or suffering from an immune dysfunction, by an effective route and in an effective amount to treat the immune dysfunction, 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;

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

are effective to treat the immune dysfunction in the subject, wherein the cells are administered adjunctively to one or more other treatments administered to the subject to treat the same thing, to treat something different, or both.

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 express telomerase.

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

5. 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.

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

7. 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.

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

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

10. A method according to claim 8, 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.

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

12. A method according to claim 9, wherein the subject is human.

13. A method according to claim 12, 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.

14. A method according to claim 12, wherein the subject will receive or has received a transplant and will be at risk for or has developed a host versus graft response or graft versus host disease, and said cells are administered adjunctively to the transplant.

15. A method according to claim 14, wherein the transplant is an organ transplant, the subject is at risk for or has developed a host versus graft response, and said cells are administered adjunctively to the transplant to treat the host versus graft response.

16. A method according to claim 14, wherein the subject is or will be treated by radiation or chemotherapy or a combination of radiation and chemotherapy, weakening the subject'"'"'s immune system, and treatment with said cells is adjunctive to the radiation, the chemotherapy, or the combination of the two.

17. A method according to claim 14, wherein said cells are administered to a subject having a compromised immune system.

18. A method according to claim 17, wherein the transplant is a bone marrow or blood transplant, the subject is at risk for or has developed graft versus host disease, and said cells are administered adjunctively to the transplant to treat the graft versus host disease.

19. A method according to claim 15, wherein the subject will be or is being treated with an immunosuppressive agent, and said treatment with said cells is adjunctive thereto.

20. A method according to claim 18 wherein the subject will be or is being treated with an immunosuppressive agent, and said treatment with said cells is adjunctive thereto.

21. A method according to claim 1, wherein the subject is at risk for or is suffering from one or more of a neoplasm, an anemia or other blood disorder, and an immune dysfunction, wherein treatment with said cells is adjunctive to a treatment thereof.

22. A method according to claim 1, wherein the subject is at risk for or is suffering from one or more of a myeloproliferative disorder, a myelodysplastic syndrome, leukemia, multiple myeloma, a lymphoma, a hemoglobinopathy, a thalassemia, a bone marrow failure syndrome, sickle cell anemia, aplastic anemia, Fanconi'"'"'s anemia, an immune hemolytic anemia, a congenital immune deficiency, or an autoimmune dysfunction, wherein treatment with said cells is adjunctive to a treatment thereof.