RAPID INFUSION OF AUTOLOGOUS BONE MARROW DERIVED STEM CELLS

• US 20140286870A1
• Filed: 06/05/2014
• Published: 09/25/2014
• Est. Priority Date: 01/12/2013
• Status: Active Grant

• Current Assignee: The Thermogenesis Corporation (Cesca Therapeutics Incorporated)
• Original Assignee: Cesca Therapeutics Incorporated
• Inventors: Harris, Kenneth, Sethi, Dalip, Ponemone, Venkatesh, Cohan, Gary R.
• Granted Patent: US 9,402,867 B2
• Time in Patent Office: Days
• US Class Current: 424/9.2
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• 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 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 38/55 Protease inhibitors
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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

Abstract

The present invention relates to a method and composition for the aspiration, processing, testing and infusion of bone marrow derived stem cells, as an adjuvant treatment in cardiovascular disorders. More specifically, the invention provides for the methods and compositions for the aspiration, analysis, processing, infusate preparation and infusion of bone-marrow derived stem cells, particularly in a rapid point-of-care environment, wherein a centrifugal fractionation and optically monitored separation of the bone marrow yield desired cellular product in the desired concentration and viscosity.

Claims

1. (canceled)

2. A method of ameliorating ischemia or a condition associated with ischemia in a subject comprising:

identifying a subject having an ischemia or a condition associated with ischemia;

providing to said subject a composition comprising;

(a) a first cell population that comprises bone marrow stem cells and/or stem cell progenitor cells,

(b) an anticoagulant, and

(c) an aqueous buffer and/or an autologous serum and/or an autologous plasma fraction,

wherein the composition has a viscosity of not more than 5.0 centipoise (cP) measured at 37°

C.; and

determining an improvement in ischemia or said condition associated with ischemia, such as by measuring or observing in said subject an increased blood flow, an improvement in left ventricle ejection fraction, an improvement in cardiac output, a reduction in cardiac scar formation, an improvement in cardiac remodeling, an increase in angiogenesis, an increase in vascularity, an improvement in neural scar formation, or an increase in amputation-free survival rate.

3. The method of claim 2, wherein the composition is provided to said subject not more than 2 hours, not more than 90 minutes or not more than 60 minutes after said first cell population that comprises bone marrow stem cells is obtained.

4. The method of claim 2, wherein the blood flow at an ischemic tissue of said subject is blocked for 1-3 minutes or 2 minutes.

5. The method of claim 2, wherein said blood flow is blocked by an inflatable balloon, wherein said balloon is inflated to block at least 80% of blood flow distal to said balloon.

6. The method of claim 2, wherein said composition is provided to said subject at a rate of no more than 2.5 mL per minute.

7. The method of claim 2, wherein said composition provided to said subject is not subjected to a maximum shear of more than 9101/second.

8. The method of claim 2, wherein said composition is provided to said subject through a catheter having a lumen size of approximately 0.36 mm.

9. The method of claim 2, wherein said composition is provided to said subject at a dose of 5 mL per dose.

10. The method of claim 2, wherein said composition is provided under a set of parameter conditions not exceeding those of Parameter Set 1, Parameter Set 2, Parameter Set 3, Parameter Set 4, Parameter Set 5 or Parameter Set 6 of Table 2.

11. The method of claim 2, wherein said composition is provided as a single dose.

12. The method of claim 2, wherein said composition is provided as at least two doses.

13. The method of claim 2, wherein said composition is provided as four doses of 5 mL each.

14. The method of claim 2, wherein said composition is provided as a single dose per day on each of multiple days.

15. The method of claim 2, wherein said composition is provided as at least two dose per day on each of multiple days.

16. The method of claim 2, wherein providing to said subject a composition is followed by a resting period of not more than 1 minute, not more than 2 minutes, not more than 3 minutes, not more than 4 minutes, or not more than 5 minutes following each dose provided.

17. The method of claim 16, wherein a last resting period is followed by a 3 mL dose of a chaser solution to evacuate any remaining cells at a rate not exceeding 2.5 mL per minute.

18. The method of claim 2, wherein said composition is provided intravascularly, intramuscularly, intra-arterially or intra-coronarily.

19. The method of claim 2, wherein the ischemia is cardiac ischemia.

20. The method of claim 2, wherein the improvement in ischemia is determined by measuring or observing in said subject an increased blood flow, an improvement in left ventricle ejection fraction, an improvement in cardiac output, a reduction in cardiac scar formation, an improvement in cardiac remodeling, an increase in angiogenesis, an increase in vascularity, an improvement in neural scar formation, or an increase in amputation-free survival rate.

21. The method of claim 19, wherein the improvement of cardiac ischemia is determined by measuring or observing in said subject an improvement in left ventricle ejection fraction, an improvement in cardiac output, a reduction in cardiac scar formation, or an improvement in cardiac remodeling.