Compositions and Methods of Vascular Injury Repair

• US 20090226402A1
• Filed: 03/10/2009
• Published: 09/10/2009
• Est. Priority Date: 11/07/2005
• Status: Active Grant

• Current Assignee: Caladrius Biosciences, Inc. (Lisata Therapeutics, Inc.)
• Original Assignee: Amorcyte, LLC (Lisata Therapeutics, Inc.)
• Inventors: Pecora, Andrew, Preti, Robert
• Granted Patent: US 8,088,370 B2
• Time in Patent Office: Days
• US Class Current: 424/93.700
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

The present invention relates to pharmaceutical compositions comprising a chemotactic hematopoietic stem cell product comprising an enriched population of CD34+ cells containing a subpopulation of cells having chemotactic activity, methods of preparing these compositions and use of these compositions to treat or repair vascular injury, including infarcted myocardium.

Claims

1. A pharmaceutical composition for repairing a vascular injury in a subject,

wherein the vascular injury is an acute myocardial infarction resulting from a natural disease process and the subject is a revascularized subject,

the pharmaceutical composition comprising:

(a) a therapeutically effective amount of a sterile isolated chemotactic hematopoietic stem cell product,

the chemotactic hematopoietic stem cell product comprising an enriched population of isolated CD34+ cells acquired from the subject and containing a subpopulation of potent cells having CXCR-4-mediated chemotactic activity; and

(b) a stabilizing amount of serum, wherein the stabilizing amount of serum is greater than 20% (v/v),

wherein the composition is administered to the subject parenterally through a catheter;

and wherein the subpopulation of potent cells having CXCR-4-mediated chemotactic activity when passed through the catheter remains potent, is at least 70% pure, at least about 70% viable, is able to form hematopoietic colonies in vitro for at least about 24 hours following acquisition from the subject of a preparation comprising the enriched population of isolated CD34+ cells.

2. The pharmaceutical composition according to claim 1, wherein the preparation comprising the enriched population of isolated CD34+ cells is purified from cellular components of a bone marrow aspirate acquired from the subject.

7. The composition according to claim 1, wherein the therapeutically effective amount of the chemotactic hematopoietic stem cell product comprises a minimum number of isolated CD34+ hematopoietic stem cells containing a subpopulation of at least 0.5×

10⁶ potent CD34+ cells having CXCR-4 mediated chemotactic activity.

9. The composition according to claim 1, wherein the enriched population of CD34+ cells is capable of forming hematopoietic colonies in vitro for at least 48 hours following acquisition and wherein at least 2% of the chemotactic activity of the subpopulation of potent cells is retained by the subpopulation of potent cells for at least 48 hours following acquisition from the subject of the preparation comprising the enriched population of isolated CD34+ cells having CXCR-4-mediated chemotactic activity.

10. The composition according to claim 1, wherein the enriched population of CD34+ cells is capable of forming hematopoietic colonies in vitro for at least 72 hours following acquisition and wherein at least 2% of the chemotactic activity of the subpopulation of potent cells is retained by the subpopulation of potent cells for at least 72 hours following acquisition from the subject of the preparation comprising the enriched population of isolated CD34+ cells having CXCR-4-mediated chemotactic activity.

13. The composition of claim 1, wherein at least 2% of the chemotactic activity of the subpopulation of potent cells is retained by the subpopulation of potent cells for at least 24 hours following acquisition from the subject of the preparation comprising the enriched population of isolated CD34+ cells having CXCR-4-mediated chemotactic activity.

20. The composition according to claim 1, wherein the composition is administered through the catheter intravascularly to an infarct-related artery.

21. The composition according to claim 1, wherein the catheter is a flow control catheter.

22. The composition according to claim 1, wherein the catheter is a balloon catheter.

23. The composition according to claim 1, wherein the catheter has an internal diameter of at least about 0.36 mm.

25. The composition according to claim 1 wherein the composition is administered through the catheter into myocardium.

27. The composition according to claim 1, wherein the pharmaceutical composition further includes at least one compatible active agent.

29. The composition according to claim 1, wherein sterility of the chemotactic hematopoietic cell product is confirmed by a method comprising the steps:

(a) centrifuging the cell product to form (i) a separated cell product comprising a pellet comprising the enriched population of isolated CD34+ cells and (ii) a supernatant;

(b) removing the supernatant of the separated cell product without disturbing the cell pellet of the separated cell product. (c) analyzing the sterility of the supernatant of the separated cell product, thereby determining the sterility of the cell pellet of the separated cell product without depleting the chemotactic hematopoietic cell product.

109. The pharmaceutical composition according to claim 1, wherein the preparation comprising the enriched population of isolated CD34+ cells is purified from peripheral blood acquired from the subject.

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