Methods of using adipose-derived regenerative cells in the treatment of peripheral vascular disease and related disorders

• US 9,480,718 B2
• Filed: 08/16/2012
• Issued: 11/01/2016
• Est. Priority Date: 12/07/2001
• Status: Expired due to Term

• Current Assignee: Lorem Vascular Pte. Ltd.
• Original Assignee: Cytori Therapeutics Incorporated
• Inventors: Fraser, John K., Hedrick, Marc H., Daniels, Eric
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US13/587,700
• Publication Number:
  US 20120315257A1
• Time in Patent Office: 1,538 Days
• Field of Search: None
• US Class Current: 1/1
• 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 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2430/00 Materials or treatment for tissue regeneration
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices artificial blood vessels A61L27/507
• 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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 2506/1384 from adipose-derived stem cells [ADSC], from adipose stromal stem cells
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells

Abstract

Cells present in adipose tissue are used to treat patients, including patients with PVD and related diseases or disorders. Methods of treating patients include processing adipose tissue to deliver a concentrated amount of stem cells obtained from the adipose tissue to a patient. The methods may be practiced in a closed system so that the stem cells are not exposed to an external environment prior to being administered to a patient. Accordingly, in a preferred method, cells present in adipose tissue are placed directly into a recipient along with such additives necessary to promote, engender or support a therapeutic benefit.

Claims

1. A method for treating peripheral vascular disease (PVD) in a subject, comprising:

identifying a subject with PVD;

obtaining a unit of adipose tissue from said subject;

processing said adipose tissue by separating adipose-derived cells comprising stem and progenitor cells from mature adipocytes and connective tissue, and washing, separating, and concentrating said adipose-derived cells from adipose tissue to obtain a concentrated population of cells comprising adipose-derived stem and endothelial progenitor cells, wherein at least 0.1% of the adipose-derived cells are adipose-derived stem cells; and

providing to the subject an amount of said concentrated population of adipose-derived cells that is sufficient to restore blood flow to an ischemic region, wherein said concentrated population of adipose-derived cells is not grown in culture.

2. The method of claim 1, further comprising providing an additive to said concentrated population of adipose-derived cells.

3. The method of claim 1, wherein said subject is human.

4. The method of claim 1, wherein said subject suffers from a defect or disorder of a blood vessel.

5. The method of claim 1, wherein said subject suffers from Peripheral Artery Disease (PAD).

6. The method of claim 1, wherein said subject suffers from at least one disease or disorder selected from the group consisting of arteriosclerosis, traumatic injury of vessels and inflammatory arteritides.

7. The method of claim 1, wherein said subject suffers from a defect or disorder of extracoronary tissue of the subject.

8. The method of claim 1, wherein said concentrated population of adipose-derived cells is provided to said subject in multiple doses.

9. The method of claim 1, further comprising providing one or more angiogenic factors to said subject or to said concentrated population of adipose-derived cells.

10. The method of claim 1, further comprising providing one or more immunosuppressive drugs to said subject or to said concentrated population of adipose-derived cells.

11. The method of claim 1, wherein said concentrated population of adipose-derived cells is provided to said subject via at least one of an intravenous, intra-muscular or subcutaneous administration route.

12. The method of claim 1, wherein the concentrated population of adipose-derived cells is provided to the subject'"'"'s vasculature.

13. The method of claim 1, wherein the concentrated population of adipose-derived cells is provided on a scaffold.

14. The method of claim 13, wherein the scaffold is resorbable in vivo.

15. The method of claim 1, wherein said adipose tissue is processed in a system configured to maintain a closed, sterile, fluid/tissue pathway, wherein said system comprises a collection chamber connected to a processing chamber.

16. The method of claim 1, wherein said processed in a system configured to maintain a closed, sterile, fluid/tissue pathway, wherein said system comprises a filter and a centrifuge.

17. The method of claim 1, wherein said processing comprises digesting said adipose tissue to create a digestate and removing mature adipocytes from said digestate.

18. The method of claim 1, further comprising measuring blood flow by a method selected from the group consisting of:

duplex ultrasonography, angiography, and magnetic resonance angiography.

19. The method of claim 1, further comprising assessing a clinical outcome selected from the group consisting of:

improved blood flow, reduction in claudication, healing of ischemic ulceration, increased oxygen content of tissue, and improvement in ankle-brachial index (ABI), or any combination thereof.

20. The method of claim 1, wherein said adipose tissue is processed in a system configured to maintain a closed, sterile, fluid/tissue pathway, wherein said system comprises:

a tissue collection chamber that is configured to receive unprocessed adipose tissue that is removed from a subject, wherein said tissue collection chamber is defined by a closed system;

a first filter that is disposed within said tissue collection chamber, wherein said first filter is configured to retain a first component of said unprocessed adipose tissue and pass a second component of said unprocessed adipose tissue, such that said first filter substantially separates said first component from said second component, and wherein said first component comprises a cell population that comprises adipose-derived stem cells and endothelial progenitor cells, and said second component comprises lipid, mature adipocytes, and saline;

a processing chamber, which is configured to receive said first component comprising said cell population that comprises adipose-derived stem cells and endothelial progenitor cells from said tissue collection chamber, wherein said processing chamber is within said closed system;

a conduit configured to allow passage of said first component comprising said cell population comprising adipose-derived stem cells and endothelial progenitor cells from said tissue collection chamber to said processing chamber while maintaining a closed system;

a cell concentrator disposed within said processing chamber, which is configured to facilitate the concentration of said first component comprising said cell population that comprises adipose-derived stem cells and endothelial progenitor cells so as to obtain a concentrated population of adipose-derived cells, wherein said cell concentrator comprises a centrifugation device or a filter; and

an outlet configured to allow the aseptic removal of said concentrated population of adipose-derived cells.

21. The method of claim 1, wherein said concentrated population of adipose-derived cells is cryopreserved.