Treatment of Diseases and Disorders Using Self-Renewing Colony Forming Cells Cultured and Expanded In Vitro

• US 20090053183A1
• Filed: 06/16/2008
• Published: 02/26/2009
• Est. Priority Date: 06/15/2007
• Status: Active Grant

• Current Assignee: Garnet Biotherapeutics Incorporated
• Original Assignee: Neuronyx, Inc. (Garnet Biotherapeutics Incorporated)
• Inventors: Ragaglia, Vanessa, Kopen, Gene, Wagner, Joseph, Heimbach, Baron, Gore, Richard S.
• Granted Patent: US 8,354,370 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 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/1722 Plasma globulins, lactoglobulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• 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 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• 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 27/02 Ophthalmic agents
• 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 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 5/0669 : Bone marrow stromal cells; Whole bone marrow isolated stem cells from bone marrow C12N5/0647, C12N5/0663

Abstract

The present invention relates to methods and uses of cells for the prevention and treatment of a wide variety of diseases and disorders and the repair and regeneration of tissues and organs using low passage and extensively passaged in vitro cultured, self-renewing, colony forming somatic cells (CF-SC). For example, adult bone marrow-derived somatic cells (ABM-SC), or compositions produced by such cells, are useful alone or in combination with other components for treating, for example, cardiovascular, neurological, integumentary, dermatological, periodontal, and immune mediated diseases, disorders, pathologies, and injuries.

Claims

1. A method of administering a therapeutically useful amount of a biological composition or compositions to an organ, tissue, or subject, comprising administering to said organ, tissue, or subject an isolated population of bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein said CF-SC do not have multipotent differentiation capacity, wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, wherein said CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β

(beta) 2-Microglobulin, and wherein said CF-SC do not express CD10, CD34, CD45, CD62L, or CD106.

5. A method of preventing tissue damage or of repairing, treating, or promoting regeneration of damaged tissue, comprising the method of claim 1.

9. A method of treating or reducing inflammation, immune, or autoimmune activity in a organ, tissue, or subject, comprising the method of claim 1.

13. The method of claim 1, wherein said CF-SC further express one or more molecules selected from the group consisting of:

a) CD29;

b) CD59;

c) CD147;

d) CD166; and

,

e) telomerase

and, wherein said CF-SC further do not express one or more molecules selected from the group consisting of;

f) CD11c;

g) CD14;

h) CD33;

i) CD62P;

j) CD80;

k) STRO-1;

l) HLA-Class-II;

m) CD178.

n) p53; and

,

o) p21.

2. A method of administering a therapeutically useful amount of a biological composition or compositions to an organ, tissue, or subject, comprising:

(a) isolating the biological composition or compositions produced by an isolated population of bone marrow-derived self-renewing colony forming somatic cells (CF-SC); and

,

(b) administering said biological composition or compositions to said organ, tissue, or subject, wherein said CF-SC do not have multipotent differentiation capacity, wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, wherein said CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β

(beta) 2-Microglobulin, and wherein said CF-SC do not express CD10, CD34, CD45, CD62L, or CD106.

6. A method of preventing tissue damage or of repairing, treating, or promoting regeneration of damaged tissue in an organ, tissue, or subject, comprising the method of claim 2.

10. A method of treating or reducing inflammation, immune, or autoimmune activity in an organ, tissue, or subject, comprising the method of claim 2.

3. A method of administering a therapeutically useful amount of a biological composition or compositions to an organ, tissue, or subject, comprising administering to said organ, tissue, or subject an isolated population of bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein said CF-SC do not have multipotent differentiation capacity, wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, and wherein said CF-SC are obtained from bone marrow by steps comprising:

i) incubating bone marrow cells under a low oxygen condition such that said bone marrow cells when allowed to adhere to a tissue culture-treated surface produce adherent colony forming units; and

,

ii) passaging cells in said adherent colony forming units at low cell seeding densities.

7. A method of preventing tissue damage or of repairing, treating, or promoting regeneration of damaged tissue in an organ, tissue, or subject, comprising the method of claim 3.

11. A method of treating or reducing inflammation, immune, or autoimmune activity in an organ, tissue, or subject, comprising the method of claim 3.

14. The method of claim 3, wherein said low oxygen condition is about 5% oxygen.

15. The method of claim 3, wherein said low oxygen condition is selected from the group consisting of:

a) less than about 20% oxygen;

b) less than about 15% oxygen;

c) less than about 10% oxygen;

d) less than about 5% oxygen;

e) between about 1 to 10% oxygen;

f) between about 2 to 7% oxygen;

g) between about 3 to 6% oxygen;

h) between about 4 to 6% oxygen; and

,

i) between about 4 to 5% oxygen.

16. The method of claim 3, wherein said low cell seeding density is less than about 200 cells/cm².

17. The method of claim 3, wherein said low cell seeding density is less than about 100 cells/cm².

18. The method of claim 3, wherein said low cell seeding density is less than about 50 cells/cm².

19. The method of claim 3, wherein said low cell seeding density is less than about 30 cells/cm².

20. The method of claim 3, wherein said low cell seeding density is selected from the group consisting of:

a) less than about 2500 cells/cm²;

b) less than about 1000 cells/cm²; and

,

c) less than about 500 cells/cm².

4. A method of administering a therapeutically useful amount of a biological composition or compositions to an organ, tissue, or subject, comprising:

(a) isolating the biological composition or compositions produced by an isolated population of bone marrow-derived self-renewing colony forming somatic cells (CF-SC); and

,

(b) administering said biological composition or compositions to said organ, tissue, or subject, wherein said CF-SC do not have multipotent differentiation capacity, wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, and wherein said CF-SC are obtained from bone marrow by steps comprising;

i) incubating bone marrow cells under a low oxygen condition such that said bone marrow cells when allowed to adhere to a tissue culture-treated surface produce adherent colony forming units; and

,

ii) passaging cells in said adherent colony forming units at low cell seeding densities.

8. A method of preventing tissue damage or of repairing, treating, or promoting regeneration of damaged tissue in an organ, tissue, or subject, comprising the method of claim 4.

12. A method of treating or reducing inflammation, immune, or autoimmune activity in a organ, tissue, or subject, comprising the method of claim 4.

21-37. -37. (canceled)

38. A composition comprising a pharmaceutically acceptable mixture of purified naturally occurring or isolated recombinant extracellular matrix or blood plasma proteins and bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, wherein said CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β

(beta) 2-Microglobulin, and wherein said CF-SC do not express CD10, CD34, CD45, CD62L, or CD106.

39. A composition comprising a pharmaceutically acceptable mixture of purified naturally occurring or isolated recombinant extracellular matrix or blood plasma proteins and a biological composition or compositions produced by an isolated population of bone marrow-derived self-renewing colony forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, wherein said CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β

(beta) 2-Microglobulin, and wherein said CF-SC do not express CD10, CD34, CD45, CD62L, or CD106.

40. A composition comprising a pharmaceutically acceptable mixture of purified naturally occurring or isolated recombinant extracellular matrix or blood plasma proteins and bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, and wherein said CF-SC are obtained from bone marrow by steps comprising:

i) incubating bone marrow cells under a low oxygen condition such that said bone marrow cells when allowed to adhere to a tissue culture-treated surface produce adherent colony forming units; and

,

ii) passaging cells in said adherent colony forming units at low cell seeding densities.

41. A composition comprising a pharmaceutically acceptable mixture of purified naturally occurring or isolated recombinant extracellular matrix or blood plasma proteins and a biological composition or compositions produced by an isolated population of bone marrow-derived self-renewing colony forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, and wherein said CF-SC are obtained from bone marrow by steps comprising:

i) incubating bone marrow cells under a low oxygen condition such that said bone marrow cells when allowed to adhere to a tissue culture-treated surface produce adherent colony forming units; and

,

ii) passaging cells in said adherent colony forming units at low cell seeding densities.

42-69. -69. (canceled)

70. A method of inducing, enhancing, and/or maintaining the generation of new red blood cells in vitro or in vivo, wherein said induction, enhancement, or maintenance is achieved by co-cultivation of hematopoietic precursor cells with bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, wherein said CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β

(beta) 2-Microglobulin, and wherein said CF-SC do not express CD10, CD34, CD45, CD62L, or CD106.

71. A method of inducing, enhancing, and/or maintaining the generation of new red blood cells in vitro or in vivo, wherein said induction, enhancement, or maintenance is achieved by co-cultivation of hematopoietic precursor cells with a biological composition or compositions produced by bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, wherein said CF-SC express CD13, CD44, CD49c, CD90, HLA Class-1 and β

(beta) 2-Microglobulin, and wherein said CF-SC do not express CD10, CD34, CD45, CD62L, or CD106.

72. (canceled)

73. A method of inducing, enhancing, and/or maintaining the generation of new red blood cells in vitro or in vivo, wherein said induction, enhancement, or maintenance is achieved by co-cultivation of hematopoietic precursor cells with bone marrow-derived self-renewing colony-forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, and wherein said CF-SC are obtained from bone marrow by steps comprising:

i) incubating bone marrow cells under a low oxygen condition such that said bone marrow cells when allowed to adhere to a tissue culture-treated surface produce adherent colony forming units; and

,

ii) passaging cells in said adherent colony forming units at low cell seeding densities.

74. A method of inducing, enhancing, and/or maintaining the generation of new red blood cells in vitro or in vivo, wherein said induction, enhancement, or maintenance is achieved by co-cultivation of hematopoietic precursor cells with a biological composition or compositions produced by an isolated population of bone marrow-derived self-renewing colony forming somatic cells (CF-SC), wherein said CF-SC have a normal karyotype, wherein said CF-SC are non-immortalized, and wherein said CF-SC are obtained from bone marrow by steps comprising:

i) incubating bone marrow cells under a low oxygen condition such that said bone marrow cells when allowed to adhere to a tissue culture-treated surface produce adherent colony forming units; and

,

ii) passaging cells in said adherent colony forming units at low cell seeding densities.

75-94. -94. (canceled)