Angiogenesis initation and growth

• US 20080217263A1
• Filed: 03/06/2007
• Published: 09/11/2008
• Est. Priority Date: 03/06/2007
• Status: Active Grant

• Current Assignee: Biomet Manufacturing, LLC (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Biomet Biologics, Inc. (Zimmer Biomet Holdings, Inc.)
• Inventors: Higgins, Joel C., Woodell-May, Jennifer E., Simon, Bruce
• Granted Patent: US 8,034,014 B2
• Time in Patent Office: Days
• US Class Current: 210/787
• 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 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/19 Platelets; Megacaryocytes
• 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 35/35 Fat tissue; Adipocytes; Stromal cells; Connective tissues adipose-derived stem cells A61K35/28; collagen A61K38/39
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/19 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61N 1/205 for promoting a biological process
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Abstract

Methods for promoting angiogenesis comprising administering platelet-rich plasma to a site and stimulating the site with an electromagnetic field. Platelets include platelet-rich plasma and compositions can further include stem cells such as adipose stromal cells and cells derived from bone marrow aspirate. Methods also comprise isolating platelets from a patient'"'"'s blood, forming a composition including the platelets, delivering the composition to a site in need of treatment, and electrically stimulating the site.

Claims

1. A method for promoting angiogenesis at a site on a patient, the method comprising:

obtaining blood compatible with the patient;

isolating platelet-rich plasma by density fractionation of said blood;

administering said platelet-rich plasma to the site;

stimulating the site with an electromagnetic field following administration of said platelet-rich plasma to the site; and

promoting angiogenesis at the site upon application of said electromagnetic field and said platelet-rich plasma to the site.

2. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, wherein isolating platelet-rich plasma by density fractionation comprises centifuging of said blood by:

loading said blood into a tube having a buoy;

spinning said tube so that said buoy defines an interface between platelet-rich plasma and platelet poor plasma contained within said blood; and

collecting said platelet-rich plasma.

3. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, wherein stimulating the site with a capacitively coupled electromagnetic field following the administration of said platelet-rich plasma includes generating in the tissue a time varying electromagnetic field having a peak amplitude of from about 0.1 to about 100 millivolts per centimeter, and having a frequency from about 1 kHz to about 200 kHz.

4. The method for promoting angiogenesis at the site on a patient as set forth in claim 1, wherein stimulating the site with an electromagnetic field following the administration of said platelet-rich plasma includes generating a pulsed electromagnetic field having a pulse duration from about 10 to 2000 microseconds.

5. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, wherein stimulating the site with an electromagnetic field following the application of platelet-rich plasma comprises:

placing at least two electrodes across the site on the patient; and

applying electrical energy to said electrodes so as to capacitively couple said electrodes and generate said electromagnetic field therebetween, said electromagnetic field passing through said platelet-rich plasma so as to promote angiogenesis at the site.

6. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, wherein stimulating the site with an electromagnetic field following the administration of said platelet-rich plasma comprises:

placing a stimulation coil proximate to the site; and

generating a pulsed electromagnetic field at the site by said stimulation coil, said pulsed electromagnetic field passing through said platelet-rich plasma so as to promote angiogenesis at the site.

7. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, wherein promoting angiogenesis of the site upon application of said electromagnetic field and said platelet-rich plasma comprises:

promoting the production of FGF-2 at the site upon the application of said electromagnetic field; and

upregulating the proliferation of endothelial cells at the site upon application of said electromagnetic field.

8. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, further comprising administering stem cells to the site, said stem selected from the group consisting of adipose stromal cells, stem cells derived from bone marrow aspirate, and combinations thereof.

9. The method for promoting angiogenesis at a site on a patient as set forth in claim 8, wherein administering stem cells to the site comprises:

performing lipoaspiration on the patient to obtain adipose tissue, said adipose tissue including adipose stem cells and adipocytes;

enzymatically digesting said adipose tissue; and

separating said adipose stem cells from said adipocytes in said enzymatically digested adipose tissue.

10. The method for promoting angiogenesis at a site on a patient as set forth in claim 8, wherein administering stem cells to the site comprises:

isolating bone marrow aspirate from the patient, said bone marrow aspirate including stem cells;

centrifuging said bone marrow aspirate to concentrate said stem cells;

isolating said concentrated stem cells derived from bone marrow aspirate.

11. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, wherein obtaining blood compatible with the patient comprises identifying and obtaining donor blood compatible with the patient by matching blood cell surface antigens.

12. The method for promoting angiogenesis at a site on a patient as set forth in claim 1, wherein administering platelet-rich plasma to the site further comprises administering an isolated angiogenic factor selected from the group consisting of angiogenin, angiopoietin-1, del-1 protein, acidic fibroblast growth factor (aFGF or FGF-1), basic fibroblast growth factor (bFGF or FGF-2), follistatin, granulocyte colony-stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin-8 (IL-8), leptin, midkine, placental growth factor, platelet-derived endothelial growth factor (PD-ECGF), platelet-derived growth factor (PDGF), pleiotrophin (PTN), progranulin, proliferin, transforming growth factor alpha (TGF-α

), transforming growth factor beta (TGF-β

), tumor necrosis factor alpha (TNF-α

), vascular endothelial growth factor (VEGF), vascular permeability factor (VPF), and combinations thereof.