Angiogenesis using placental stem cells

• US 9,254,302 B2
• Filed: 04/06/2011
• Issued: 02/09/2016
• Est. Priority Date: 04/07/2010
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Abbot, Stewart, Edinger, James W., Francki, Aleksandar, Hariri, Robert J., Jankovic, Vladimir, Kaplunovsky, Aleksandr, Labazzo, Kristen, Law, Eric, Padliya, Neerav D., Paredes, Jennifer, Wang, Jia-Lun
• Primary Examiner(s): Ton, Thaian N
• Application Number:
  US13/081,415
• Publication Number:
  US 20110250182A1
• Time in Patent Office: 1,770 Days
• US Class Current: 1/1
• 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 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• 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: A61P 9/12 Antihypertensives
• 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 of treating individuals having diseases or disorders of the circulatory system, using placental cells, e.g., the placental stem cells and placental multipotent cells (PDACs) described herein, and populations of such placental cells. The invention also provides methods of angiogenesis using such cells or populations of cells comprising such cells.

Claims

1. A method of treating an individual having peripheral arterial disease, critical limb ischemia, diabetic ulcer, or peripheral vascular disease,

comprising:

administering to the individual a population of isolated placental cells, wherein said placental cells (i) adhere to tissue culture plastic;

(ii) are CD10+, CD34−

, CD105+, and CD200+ as determined by flow cytometry, and (iii) promote the proliferation of endothelial cells;

promote the formation of sprouts or tube-like structures in a population of endothelial cells;

or promote the migration of endothelial cells;

wherein said administration of cells is in an amount and for a time sufficient for detectable improvement of one or more symptoms of peripheral arterial disease, critical limb ischemia, diabetic ulcer, or peripheral vascular disease.

2. The method of claim 1, wherein said individual has peripheral vascular disease.

3. The method of claim 2, wherein said symptom of peripheral vascular disease is cold, tingling feet that turn red upon dangling;

pain;

or weakness and tiredness in the legs.

4. The method of claim 2, wherein said placental cells have been passaged at least one time prior to administration to said individual.

5. The method claim of claim 1, wherein said individual has critical limb ischemia.

6. The method of claim 5, wherein said symptom of critical limb ischemia is ischemic rest pain;

severe pain in the legs and feet while the individual is not moving;

non-healing sores on the feet or legs;

pain or numbness in the feet;

shiny, smooth, dry skin of the legs or feet;

thickening of the toenails;

absent or diminished pulse in the legs or feet;

open sores;

skin infections or ulcers that do not heal;

or dry gangrene of the legs or feet.

7. The method of claim 5, wherein said placental cells have been passaged at least one time prior to administration to said individual.

8. The method of claim 1, wherein said individual has peripheral arterial disease.

9. The method of claim 1, wherein said placental cells are administered intravenously, intra-arterially, intramuscularly, intradermally, subcutaneously, or locally.

10. The method of claim 1, comprising administration of about 1×

10⁵, 5×

10⁵, 1×

10⁶, 5×

10⁶, 1×

10⁷, 5×

10⁷, 1×

10⁸, 5×

10⁸, 1×

10⁹, 5×

10⁹, or 1×

10¹⁰ placental cells.

11. The method of claim 1, wherein said individual has a diabetic ulcer.

12. The method of claim 1, wherein said placental cells have been passaged at least one time prior to administration to said individual.

13. The method of claim 11, wherein said placental cells have been passaged at least one time prior to administration to said individual.

14. A method of treating an individual having a disruption of blood flow in or around a limb, wherein said disruption of blood flow in or around a limb is caused by peripheral arterial disease, critical limb ischemia, or peripheral vascular disease, comprising:

administering to the individual a therapeutically effective amount of placental cells, wherein said placental cells (i) adhere to tissue culture plastic;

(ii) are CD10+, CD34−

, CD105+, and CD200+ as determined by flow cytometry, and (iii) promote the proliferation of endothelial cells;

promote the formation of sprouts or tube-like structures in a population of endothelial cells;

or promote the migration of endothelial cells;

wherein said administration of cells results in improvement of blood flow in or around the limb.

15. The method of claim 14, wherein said disruption of blood flow in or around a limb is peripheral vascular disease.

16. The method of claim 14, wherein said disruption of blood flow in or around a limb is critical limb ischemia.

17. The method of claim 14, wherein said disruption of blood flow in or around a limb is peripheral arterial disease.

18. The method of claim 14, wherein said placental cells are administered intravenously, intra-arterially, intramuscularly, intradermally, subcutaneously, or locally.

19. The method of claim 14, comprising administration of about 1×

10⁵, 5×

10⁵, 1×

10⁶, 5×

10⁶, 1×

10⁷, 5×

10⁷, 1×

10⁸, 5×

10⁸, 1×

10⁹, 5×

10⁹, or 1×

10¹⁰ placental cells.

20. The method of claim 14 wherein said placental cells have been passaged at least one time prior to administration to said individual.