Compositions and methods for treating progressive myocardial injury due to a vascular insufficiency
First Claim
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1. A method of treating a progressive myocardial injury that is an adverse consequence of a vascular insufficiency affecting coronary circulation of a subject, comprising(a) first, acquiring from the subject, under sterile conditions, a population of mononuclear cells comprising CD34+cells;
- (b) second, sterilely enriching the population of mononuclear cells for CD34+cells, so that at least 70% of the cells comprising CD34+cells;
(c) third, at least 24 hours after step (a), passing a first portion of the enriched population produced in step (b) through a catheter and confirming that(i) at least some of the cells passed through said catheter have CXCR-4-mediated chemotactic activity and move in response to SDF-1 in vitro;
(ii) at least some of the cells passed through said catheter can form hematopoietic colonies in vitro; and
(iii) at least 70% of the cells passed through said catheter are viable;
(d) fourth, formulating for parenteral delivery through a catheter a sterile pharmaceutical composition comprising;
(i) a second portion of the enriched population produced in step (b), which contains at least 0.5×
106 potent CD34+/CXCR-4+cells that have CXCR-4mediated chemotactic activity and that move in response to SDF-1; and
(ii) a stabilizing amount of serum of at least 10% relative to the volume of the sterile pharmaceutical composition, wherein the stabilizing amount is effective to retain the CXCR-4-mediated chemotactic activity and hematopoietic-colony-forming activity of the CD34+/CXCR-4+cells in the second portion of (d)(i);
(e) fifth, administering the sterile pharmaceutical composition to the subject parenterally on a first infusion date; and
(f) sixth, repeating steps (b)-(d), in order, and optionally step (a), at a plurality of infusion dates to treat ongoing vascular insufficiency affecting coronary circulation,thereby improving myocardial perfusion and preserving existing myocardiocytes and their function during the subject'"'"'s lifetime.
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Abstract
The described invention provides methods and regimens for treating adverse consequences of a persistent and progressive myocardial injury-due to a vascular insufficiency that occurs early or late in a subject in need thereof, and progressive myocardial injury-preventing compositions that contain a chemotactic hematopoietic stem cell product, and, optionally, an additional active agent.
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Citations
33 Claims
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1. A method of treating a progressive myocardial injury that is an adverse consequence of a vascular insufficiency affecting coronary circulation of a subject, comprising
(a) first, acquiring from the subject, under sterile conditions, a population of mononuclear cells comprising CD34+cells; -
(b) second, sterilely enriching the population of mononuclear cells for CD34+cells, so that at least 70% of the cells comprising CD34+cells; (c) third, at least 24 hours after step (a), passing a first portion of the enriched population produced in step (b) through a catheter and confirming that (i) at least some of the cells passed through said catheter have CXCR-4-mediated chemotactic activity and move in response to SDF-1 in vitro; (ii) at least some of the cells passed through said catheter can form hematopoietic colonies in vitro; and (iii) at least 70% of the cells passed through said catheter are viable; (d) fourth, formulating for parenteral delivery through a catheter a sterile pharmaceutical composition comprising; (i) a second portion of the enriched population produced in step (b), which contains at least 0.5×
106 potent CD34+/CXCR-4+cells that have CXCR-4mediated chemotactic activity and that move in response to SDF-1; and(ii) a stabilizing amount of serum of at least 10% relative to the volume of the sterile pharmaceutical composition, wherein the stabilizing amount is effective to retain the CXCR-4-mediated chemotactic activity and hematopoietic-colony-forming activity of the CD34+/CXCR-4+cells in the second portion of (d)(i); (e) fifth, administering the sterile pharmaceutical composition to the subject parenterally on a first infusion date; and (f) sixth, repeating steps (b)-(d), in order, and optionally step (a), at a plurality of infusion dates to treat ongoing vascular insufficiency affecting coronary circulation, thereby improving myocardial perfusion and preserving existing myocardiocytes and their function during the subject'"'"'s lifetime. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
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Specification