Method of providing readily available cellular material derived from peripheral blood, and a composition thereof

• US 20060193839A1
• Filed: 02/27/2006
• Published: 08/31/2006
• Est. Priority Date: 02/28/2005
• Status: Abandoned Application

• Current Assignee: Regenetech, Inc.
• Original Assignee: Regenetech, Inc.
• Inventors: Rudd, Donnie
• Application Number:
  US11/363,702
• Publication Number:
  US 20060193839A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 33/34 Copper; Compounds thereof
• 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 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2501/125 : Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/22 : Colony stimulating factors (G-CSF, GM-CSF)
• CPC Class Codes: C12N 5/0647 : Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention is directed to the TVEMF-expansion of mammalian peripheral blood stem cells, preferably CD34+/CD38− cells, to compositions resulting from the TVEMF-expanded cells, and to a method of treating disease or repairing tissue with the compositions.

Claims

1. Peripheral blood stem cells from a mammal,

wherein said peripheral blood stem cells are in a number per volume that is at least 7 times greater than naturally-occurring peripheral blood;

and

wherein the peripheral blood stem cells have a three-dimensional geometry and cell-to-cell support and cell-to-cell geometry that is essentially the same as stem cells of naturally-occurring peripheral blood.

2. A composition comprising the peripheral blood stem cells of claim 1 and an acceptable carrier.

3. A composition of claim 2, wherein said acceptable carrier is at least one of the group consisting of plasma, blood, albumin, cell culture medium, buffer and cryopreservative;

and

wherein said composition optionally further comprises at least one of a growth factor, a copper chelating agent, and a hormone.

4. The composition of claim 3, wherein said growth factor if present is G-CSF and wherein said copper chelating agent if present is D-penicillamine.

5. The composition of claim 2, wherein said composition is at a temperature sufficient to cryogenically preserve the peripheral blood stem cells.

6. The composition according to claim 2, wherein a cryopreservative is present in an amount sufficient for cryopreservation of said cells, and wherein said composition is at a temperature of from about −

120°

C. to about −

196°

C.

7. The composition according to claim 6, wherein said temperature is from about −

130°

C. to about −

150°

C.

8. The composition according to claim 2, further comprising a pharmaceutically acceptable carrier.

9. The composition according to claim 3, wherein said composition comprises a total amount of a cryopreservative selected from the group consisting of 20 to 40% dimethyl sulfoxide solution in 60 to 80% amino acid-glucose solution;

15 to 25% hydroxyethyl starch solution;

4 to 6% glycerol, 3 to 5% glucose and 6 to 10% dextran T10;

15 to 25% polyethylene glycol; and

75 to 85% amino acid-glucose solution.

10. The composition of claim 2, wherein said composition is free of toxic material.

42. A method of repairing tissue of a mammal comprising the step of administering to the mammal a therapeutically effective amount of a composition comprising the peripheral blood stem cells of claim 1 and a pharmaceutically acceptable carrier.

48. A method of treating a disease of a mammal comprising the step of administering to the mammal a therapeutically effective amount of a composition comprising the peripheral blood stem cells of claim 1 and a pharmaceutically acceptable carrier.

11. Peripheral blood stem cells from a mammal, wherein said peripheral blood stem cells are TVEMF-expanded.

12. The TVEMF-expanded peripheral blood stem cells of claim 11, wherein the number of TVEMF-expanded peripheral blood stem cells per volume is at least 2 times greater than the number of stem cells per volume of the peripheral blood from which the TVEMF-expanded peripheral blood stem cells are derived.

13. The TVEMF-expanded peripheral blood stem cells of claim 12, wherein the number of TVEMF-expanded peripheral blood stem cells per volume is at least 7 times greater.

14. A composition comprising the peripheral blood stem cells of claim 13 and an acceptable carrier.

15. A composition comprising the TVEMF-expanded peripheral blood stem cells of claim 13 wherein said acceptable carrier is at least one of the group consisting of plasma, blood, albumin, cell culture medium, buffer and cryopreservative;

and wherein said composition optionally further comprises at least one of a growth factor, a copper chelating agent, and a hormone.

16. The composition of claim 15, wherein said growth factor if present is G-CSF and wherein said copper chelating agent if present is D-penicillamine.

17. The composition according to claim 14, wherein said composition further comprises a total amount of cryopreservative selected from the group consisting of 20 to 40% dimethyl sulfoxide solution in 60 to 80% amino acid-glucose solution;

15 to 25% hydroxyethyl starch solution;

4 to 6% glycerol, 3 to 5% glucose and 6 to 10% dextran T10;

15 to 25% polyethylene glycol; and

75 to 85% amino acid-glucose solution.

18. The composition of claim 14, wherein said composition is at a temperature sufficient to cryogenically preserve the peripheral blood stem cells.

19. The composition according to claim 14, wherein a cryopreservative is present and wherein said composition is at a temperature of from about −

120°

C. to about −

196°

C.

20. The composition according to claim 14, wherein said temperature is from about −

130°

C. to about −

150°

C.

21. The composition of claim 14, wherein said composition is free of toxic material.

43. A method of repairing tissue of a mammal comprising the step of administering to the mammal a therapeutically effective amount of a composition comprising the TVEMF-expanded peripheral blood stem cells of claim 11 and a pharmaceutically acceptable carrier.

44. The method of claim 43, wherein the tissue to be repaired is human tissue.

45. The method of claim 44, wherein the mammal is the source of the peripheral blood stem cells prior to TVEMF-expansion.

46. The method of claim 44, wherein the tissue to be repaired is at least one selected from the group consisting of liver tissue, heart tissue, hematopoietic tissue, blood vessels, skin tissue, muscle tissue, gut tissue, pancreatic tissue, central nervous system cells, bone, cartilage tissue, connective tissue, pulmonary tissue, spleen tissue and brain tissue.

47. The method of claim 43, wherein the amount of TVEMF-expanded peripheral blood stem cells to be administered to the mammal is at least 20 ml of a composition having 107 to 109 stem cells/ml.

49. A method of treating a disease of a mammal comprising the step of administering to the mammal a therapeutically effective amount of a composition comprising the TVEMF-expanded peripheral blood stem cells of claim 11 and a pharmaceutically acceptable carrier.

50. The method of claim 49, wherein the mammal is a human and wherein the mammal is the source of the peripheral blood stem cells prior to TVEMF-expansion.

51. The method of claim 50, wherein the amount of TVEMF-expanded peripheral blood stem cells to be administered to the mammal is at least 20 ml of a composition having 10⁷ to 10⁹ stem cells/ml.

52. The method of claim 50, wherein the disease is selected from at least one of the group consisting of diseases resulting from a failure or dysfunction of normal blood cell production and maturation, hyperproliferative stem cell disorders, aplastic anemia, pancytopenia, thrombocytopenia, red cell aplasia, Blackfan-Diamond syndrome due to drugs, radiation, or infection, idiopathic;

hematopoietic malignancies, acute lymphoblastic (lymphocytic) leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute malignant myelosclerosis, multiple myeloma, polycythemia vera, agnogenic myelometaplasia, Waldenstrom'"'"'s macroglobulinemia, Hodgkin'"'"'s lymphoma, non-Hodgkins'"'"'s lymphoma;

immunosuppression in patients with malignant, solid tumors, malignant melanoma, carcinoma of the stomach, ovarian carcinoma, breast carcinoma, small cell lung, carcinoma, retinoblastoma, testicular carcinoma, glioblastoma, rhabdomyosarcoma, neuroblastoma, Ewing'"'"'s sarcoma, lymphoma;

autoimmune diseases, rheumatoid arthritis, diabetes type I, chronic hepatitis, multiple sclerosis, and systemic lupus erythematosus;

genetic (congenital) disorders, anemias, familial aplastic, Fanconi'"'"'s syndrome, Bloom'"'"'s syndrome, pure red cell aplasia (PRCA), dyskeratosis congenital, Blackfan-Diamond syndrome, congenital dyserythropoietic syndromes I-IV, Chwachmann-Diamond syndrome, dihydrofolate reductase deficiencies, formamino transferase deficiency, Lesch-Nyhan syndrome, congenital spherocytosis, congenital elliptocytosis, congenital stomatocytosis, congenital Rh null disease, paroxysmal nocturnal hemoglobinuria, G6PD (glucose-6-phosphate dehydrogenase), variants 1,2,3, pyruvate kinase deficiency, congenital erythropoietin sensitivity, deficiency, sickle cell disease and trait, thalassemia alpha, beta, gamma met-hemoglobinemia, congenital disorders of immunity, severe combined immunodeficiency disease, (SCID), bare lymphocyte syndrome, ionophore-responsive combined, immunodeficiency, combined immunodeficiency with a capping abnormality, nucleoside phosphorylase deficiency, granulocyte actin deficiency, infantile agranulocytosis, Gaucher'"'"'s disease, adenosine deaminase deficiency, Kostmann'"'"'s syndrome, reticular dysgenesis, congenital leukocyte dysfunction syndromes;

osteopetrosis, myelosclerosis, acquired hemolytic anemias, acquired immunodeficiencies, infectious disorders causing primary or secondary immunodeficiencies, bacterial infections (e.g., Brucellosis, Listerosis, tuberculosis, leprosy), parasitic infections (e.g., malaria, Leishmaniasis), fungal infections, disorders involving disproportions in lymphoid cell sets and impaired immune functions due to aging phagocyte disorders, Kostmann'"'"'s agranulocytosis, chronic granulomatous disease, Chediak-Higachi syndrome, neutrophil actin deficiency, neutrophil membrane GP-180 deficiency, metabolic storage diseases, mucopolysaccharidoses, mucolipidoses, miscellaneous disorders involving immune mechanisms, Wiskott-Aldrich Syndrome, and alpha 1-antitrypsin deficiency.

22. A process for preparing a peripheral blood stem cell composition comprising the steps of:

a. placing a peripheral blood mixture in a culture chamber of a TVEMF-bioreactor; and

b. subjecting the peripheral blood mixture to a TVEMF and TVEMF-expanding the peripheral blood stem cells in the TVEMF-bioreactor to prepare the peripheral blood stem cell composition.

23. The process according to claim 22, wherein said TVEMF is about 0.05 to about 6.0 gauss.

24. The process according to claim 22, wherein said TVEMF-expanding continues until the number per volume of TVEMF-expanded peripheral blood stem cells is more than 7 times the number per volume of peripheral blood stem cells placed in the TVEMF-bioreactor.

25. The process according to claim 22, further comprising collecting peripheral blood prior to placing the peripheral blood mixture in a TVEMF-bioreactor.

26. The process of claim 25, wherein said peripheral blood is human peripheral blood.

27. The process according to claim 22, further comprising collecting thawed cryopreserved peripheral blood from a peripheral blood storage facility prior to adding the peripheral blood to the peripheral blood mixture.

28. The process of claim 22, further comprising a step of removing toxic material from the peripheral blood mixture prior to TVEMF-expansion.

29. The process of claim 22, wherein the TVEMF-bioreactor has an integral TVEMF source.

30. The process of claim 22, wherein the TVEMF-bioreactor has an adjacent TVEMF source.

31. The process of claim 22, wherein the peripheral blood mixture comprises CD34+/CD38-peripheral blood stem cells separated from other peripheral blood components.

32. The process of claim 22, wherein the peripheral blood mixture comprises a buffy coat separated from other peripheral blood components.

33. The process of claim 22, wherein the peripheral blood mixture comprises peripheral blood free of red blood cells.

34. The process of claim 22, further comprising the steps of transferring the TVEMF-expanded cells of the peripheral blood stem cell composition into a cryogenic container having a temperature, and lowering the temperature of the cryogenic container to a temperature of from −

120°

C. to −

196°

C. at a controlled rate.

35. The process of claim 34, further comprising a step of removing toxic material from the peripheral blood stem cell composition prior to lowering the temperature to a temperature of from −

120°

C. to −

196°

C. at a controlled rate.

36. The process of claim 34, further comprising, after the step of lowering the temperature, a step of maintaining the temperature of the cryogenic container to a temperature of from −

120°

C. to −

196°

C., for a period of time.

37. The process of claim 36, wherein said period of time is at least 1 year.

38. The process of claim 36, further comprising, after said lowering and maintaining of temperature, a step of increasing the temperature of the cryogenic container at a controlled rate to a temperature suitable for introducing the peripheral blood stem cell composition to a mammal.

39. The process of claim 38, wherein toxic material has been removed from said increased temperature peripheral blood stem cell composition.

40. The process of claim 34, further comprising the step of adding a cryopreservative to the TVEMF-expanded cells of the peripheral blood stem cell composition before the step of lowering the temperature.

41. A composition comprising peripheral blood stem cells and an acceptable carrier prepared by the process according to claim 22.

53. A method of researching a disease state comprising introducing a TVEMF-expanded stem cell into a test system for the disease state.

54. The method of claim 53 wherein said disease state is at least one of the group consisting of diseases resulting from a failure or dysfunction of normal blood cell production and maturation, hyperproliferative stem cell disorders, aplastic anemia, pancytopenia, thrombocytopenia, red cell aplasia, Blackfan-Diamond syndrome due to drugs, radiation, or infection, idiopathic;

hematopoietic malignancies, acute lymphoblastic (lymphocytic) leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute malignant myelosclerosis, multiple myeloma, polycythemia vera, agnogenic myelometaplasia, Waldenstrom'"'"'s macroglobulinemia, Hodgkin'"'"'s lymphoma, non-Hodgkins'"'"'s lymphoma;

immunosuppression in patients with malignant, solid tumors, malignant melanoma, carcinoma of the stomach, ovarian carcinoma, breast carcinoma, small cell lung, carcinoma, retinoblastoma, testicular carcinoma, glioblastoma, rhabdomyosarcoma, neuroblastoma, Ewing'"'"'s sarcoma, lymphoma;

autoimmune diseases, rheumatoid arthritis, diabetes type I, chronic hepatitis, multiple sclerosis, and systemic lupus erythematosus;

genetic (congenital) disorders, anemias, familial aplastic, Fanconi'"'"'s syndrome, Bloom'"'"'s syndrome, pure red cell aplasia (PRCA), dyskeratosis congenital, Blackfan-Diamond syndrome, congenital dyserythropoietic syndromes I-IV, Chwachmann-Diamond syndrome, dihydrofolate reductase deficiencies, formamino transferase deficiency, Lesch-Nyhan syndrome, congenital spherocytosis, congenital elliptocytosis, congenital stomatocytosis, congenital Rh null disease, paroxysmal nocturnal hemoglobinuria, G6PD (glucose-6-phosphate dehydrogenase), variants 1,2,3, pyruvate kinase deficiency, congenital erythropoietin sensitivity, deficiency, sickle cell disease and trait, thalassemia alpha, beta, gamma met-hemoglobinemia, congenital disorders of immunity, severe combined immunodeficiency disease, (SCID), bare lymphocyte syndrome, ionophore-responsive combined, immunodeficiency, combined immunodeficiency with a capping abnormality, nucleoside phosphorylase deficiency, granulocyte actin deficiency, infantile agranulocytosis, Gaucher'"'"'s disease, adenosine deaminase deficiency, Kostmann'"'"'s syndrome, reticular dysgenesis, congenital leukocyte dysfunction syndromes;

osteopetrosis, myelosclerosis, acquired hemolytic anemias, acquired immunodeficiencies, infectious disorders causing primary or secondary immunodeficiencies, bacterial infections (e.g., Brucellosis, Listerosis, tuberculosis, leprosy), parasitic infections (e.g., malaria, Leishmaniasis), fungal infections, disorders involving disproportions in lymphoid cell sets and impaired immune functions due to aging phagocyte disorders, Kostmann'"'"'s agranulocytosis, chronic granulomatous disease, Chediak-Higachi syndrome, neutrophil actin deficiency, neutrophil membrane GP-180 deficiency, metabolic storage diseases, mucopolysaccharidoses, mucolipidoses, miscellaneous disorders involving immune mechanisms, Wiskott-Aldrich Syndrome, and alpha 1-antitrypsin deficiency.

55. Bone marrow stem cells from a mammal, wherein said bone marrow stem cells are TVEMF-expanded.