TREATMENT OF STROKE USING ISOLATED PLACENTAL CELLS

• US 20100047351A1
• Filed: 08/20/2009
• Published: 02/25/2010
• Est. Priority Date: 08/20/2008
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Ajai, Pal, ZEITLIN, Andy
• Granted Patent: US 8,828,376 B2
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• 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 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 5/0605 : Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly

Abstract

Provided herein are methods for the treatment of stroke comprising administering to a stroke victim placental stem cells, populations of cells comprising placental stem cells, and/or compositions comprising placental stem cells.

Claims

1. A method of treating an individual having a disruption in the flow of blood in or around the brain, comprising administering to said individual an effective amount of isolated human adherent placental cells that are:

CD10⁺,CD34⁻

, and CD105⁺;

CD200⁺ and HLA-G⁺;

CD73⁺, CD105⁺, and CD200⁺;

CD200⁺ and OCT-4⁺;

CD73⁺, CD105⁺ and HLA-G⁺;

CD73⁺ and CD105⁺ and facilitate the formation of one or more embryoid-like bodies in a population of placental cells comprising said stem cell when said population is cultured under conditions that allow the formation of an embryoid-like body;

or

OCT-4⁺ and facilitate the formation of one or more embryoid-like bodies in a population of placental cells comprising the stem cell when said population is cultured under conditions that allow formation of embryoid-like bodies;

or any combination thereof.

2. The method of claim 1, wherein said CD10⁺, CD34⁻

, CD105⁺ cells are additionally CD200⁺.

3. The method of claim 2, wherein said CD10⁺, CD34⁻

, CD105⁺, CD200⁺ cells are additionally CD45⁻

or CD90⁺.

4. The method of claim 3, wherein said CD10⁺, CD34⁻

, CD105⁺, CD200⁺ cells are additionally CD45⁻

and CD90⁺.

5. The method of claim 1, wherein said therapeutically effective amount is a number of said cells that results in elimination of, a detectable improvement in, lessening of the severity of, or slowing of the progression of one or more symptoms of disruption in the flow of blood in or around the brain exhibited by said individual.

6. The method of claim 5, wherein said symptom is hemiplegia or hemiparesis.

7. The method of claim 5, wherein said symptom is muscle weakness of the face;

numbness;

reduction in sensation;

altered smell, taste, hearing, or vision;

loss of smell, taste, hearing, or vision;

drooping of an eyelid (ptosis);

detectable weakness of an ocular muscle;

decreased gag reflex;

decreased ability to swallow;

decreased pupil reactivity to light;

decreased sensation of the face;

decreased balance;

nystagmus;

altered breathing rate;

altered heart rate;

weakness in sternocleidomastoid muscle with decreased ability or inability to turn the head to one side;

weakness in the tongue;

aphasia (inability to speak or understand language);

apraxia (altered voluntary movements);

a visual field defect;

a memory deficit;

hemineglect or hemispatial neglect (deficit in attention to the space on the side of the visual field opposite the lesion);

disorganized thinking;

confusion;

development of hypersexual gestures;

anosognosia (persistent denial of the existence of a deficit);

difficulty walking;

altered movement coordination;

vertigo;

disequilibrium;

loss of consciousness;

headache;

or vomiting, wherein said symptom is caused by disruption in the flow of blood in or around the brain.

8. The method of claim 1, wherein said isolated human adherent placental cells are CD10⁺, CD34⁻

, CD105⁺, CD200⁺.

9. The method of claim 8, wherein said isolated human adherent placental cells are additionally CD45⁻

and CD90⁺.

10. The method of claim 1, wherein said isolated human adherent placental cells are CD200⁺ and HLA-G⁺.

11. The method of claim 10, wherein said CD200⁺, HLA-G⁺ cells are additionally CD34⁻

, CD38⁻

, CD45⁻

, CD73⁺ and CD105⁺.

12. The method of claim 1, wherein said isolated human adherent placental cells are CD73⁺, CD105⁺ and HLA-G⁺.

13. The method of claim 11, wherein said CD73⁺, CD105⁺ and HLA-G⁺ cells are additionally CD34⁻

, CD45⁻

, OCT-4⁺ and CD200⁺.

14. The method of claim 1, wherein said CD73⁺, CD105⁺, and CD200⁺ cells are additionally CD34⁻

, CD38⁻

, CD45⁻

, and HLA-G⁺.

15. The method of claim 1, wherein said CD200⁺, OCT-4⁺ cells are additionally CD34⁻

, CD38⁻

, CD45⁻

, CD73⁺, CD105⁺ and HLA-G⁺.

16. The method of claim 1, wherein said CD73⁺ and CD105⁺ cells are additionally OCT-4⁺, CD34⁻

, CD38⁻

and CD45⁻

.

17. The method of claim 1, wherein said OCT-4⁺ cells are additionally CD73⁺, CD105⁺, CD200⁺, CD34⁻

, CD38⁻

, and CD45⁻

.

18. The method of claim 1, wherein said isolated human adherent placental cells are contained within a population of cells, at least 80% of which are isolated human adherent placental cells.

19. The method of claim 1, wherein said isolated human adherent placental cells are contained within a population of cells, at least 90% of which are said isolated human adherent placental cells.

21. The method of claim 1, wherein said disruption of the flow of blood is stroke.

22. The method of claim 21, wherein said stroke is ischemic stroke.

23. The method of claim 21, wherein said stroke is hemorrhagic stroke.

24. The method of claim 1, wherein said disruption is a hematoma.

25. The method of claim 24, wherein said hematoma is a dural hematoma, a subdural hematoma, or a subarachnoid hematoma.

26. The method of claim 1, wherein said disruption is vasospasm.

27. The method of claim 1, wherein said isolated placental cells are administered by bolus injection.

28. The method of claim 1, wherein said isolated placental cells are administered by intravenous infusion.

29. The method of claim 1, wherein said isolated placental cells are administered intracranially.

30. The method of claim 29, wherein said isolated placental cells are administered within an area of ischemia.

31. The method of claim 29, wherein said isolated placental cells are administered to an area peripheral to an ischemia.

32. The method of claim 1, wherein said isolated placental cells are administered intraperitoneally, intramuscularly, intradermally or intraocularly.

33. The method of claim 1, wherein said isolated adherent placental cells are administered by surgical implantation of a composition comprising said isolated human adherent placental cells.

34. The method of claim 33, wherein said composition is a matrix or scaffold.

35. The method of claim 34, wherein said matrix or scaffold is a hydrogel.

36. The method of claim 34, wherein said matrix or scaffold is a decellularized tissue.

37. The method of claim 34, wherein said matrix or scaffold is a synthetic biodegradable composition.

38. The method of claim 1, wherein said isolated placental cells are administered once to said individual.

39. The method of claim 1, wherein said isolated placental cells are administered to said individual a plurality of times.

40. The method of claim 1, wherein said administering comprises administering between about 1×

10⁴ and 1×

10⁵ isolated placental cells per kilogram of said individual.

41. The method of claim 1, wherein said administering comprises administering between about 1×

10⁵ and 1×

10⁶ isolated placental cells per kilogram of said individual.

42. The method of claim 1, wherein said administering comprises administering between about 1×

10⁶ and 1×

10⁷ isolated placental cells per kilogram of said individual.

43. The method of claim 1, wherein said administering comprises administering between about 1×

10⁷ and 1×

10⁸ isolated placental cells per kilogram of said individual.

44. The method of claim 1, wherein said administering comprises administering between about 5×

10⁷ and 3×

10⁹ isolated placental cells intravenously.

45. The method of claim 44, wherein said administering comprises administering about 9×

10⁸ isolated placental cells.

46. The method of claim 44, wherein said administering comprises administering about 1.8×

10⁹ isolated placental cells.

47. The method of claim 1, wherein said administering comprises administering between about 5×

10⁷ and 1×

10⁸ isolated placental cells intracranially.

48. The method of claim 47, wherein said administering comprises administering about 9×

10⁷ isolated placental cells.

49. The method of claim 1, comprising administering a second therapeutic agent to said individual.

50. The method of claim 49, wherein said second therapeutic agent is a neuroprotective agent.

51. The method of claim 50, wherein said second therapeutic agent is NXY-059 (disulfonyl derivative of phenylbutylnitrone).

52. The method of claim 49, wherein said second therapeutic agent is a thrombolytic agent.

53. The method of claim 52, wherein said thrombolytic agent is tissue plasminogen activator (tPA).

54. The method of claim 1, wherein said isolated placental cells are administered to said individual within 48 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual.

55. The method of claim 1, wherein said isolated placental cells are administered to said individual within 24 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual.

56. The method of claim 1, wherein said isolated placental cells are administered to said individual within 12 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual.

57. The method of claim 1, wherein said isolated placental cells are administered to said individual within 3 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual.

58. The method of claim 1, wherein said isolated placental cells were cryopreserved prior to said administering.

59. The method of claim 1, wherein said isolated human adherent placental cells are obtained from a placental stem cell bank.

20. A method of treating an individual having a disruption in the flow of blood in or around the brain, comprising administering to said individual an effective amount of isolated human adherent placental cells, wherein said cells express one or more genes at a detectably higher level than a bone marrow-derived mesenchymal stem cell,

wherein said one or more genes are one or more of ACTG2, ADARB1, AMIGO2, ARTS-1, B4GALT6, BCHE, C11orf9, CD200, COL4A1, COL4A2, CPA4, DMD, DSC3, DSG2, ELOVL2, F2RL1, FLJ10781, GATA6, GPR126, GPRC5B, ICAM1, IER3, IGFBP7, IL1A, IL6, IL18, KRT18, KRT8, LIPG, LRAP, MATN2, MEST, NFE2L3, NUAK1, PCDH7, PDLIM3, PKP2, RTN1, SERPINB9, ST3GAL6, ST6GALNAC5, SLC12A8, TCF21, TGFB2, VTN, and ZC3H12A, and

wherein said bone marrow-derived stem cell has undergone a number of passages in culture that is equivalent to the number of passages said placental stem cell has undergone.

60. The method of claim 20, wherein said isolated human adherent placental cells express said one or more genes when cultured for about 3 to about 35 population doublings in a medium comprising 60% DMEM-LG and 40% MCDB-201;

2% fetal calf serum;

1×

insulin-transferrin-selenium (ITS);

1×

linoleic acid-bovine serum albumin (LA-BSA);

10<sup>−

9</sup> M dexamethasone;

10<sup>−

4</sup> M ascorbic acid 2-phosphate;

epidermal growth factor 10 ng/mL; and

platelet-derived growth factor (PDGF-BB) 10 ng/mL.

61. The method of claim 20 wherein said isolated human adherent placental cells express said one or more genes when cultured for from about 3 to about 35 population doublings in a medium comprising 60% DMEM-LG (Gibco) and 40% MCDB-201 (Sigma);

2% fetal calf serum (Hyclone Labs.);

1×

insulin-transferrin-selenium (ITS);

1×

linoleic acid-bovine serum albumin (LA-BSA);

10<sup>−

9</sup> M dexamethasone (Sigma);

10<sup>−

4</sup> M ascorbic acid 2-phosphate (Sigma);

epidermal growth factor 10 ng/mL (R&

D Systems); and

platelet-derived growth factor (PDGF-BB) 10 ng/mL (R&

D Systems).