Compositions and methods of vascular injury repair
Inventors
Pecora, Andrew L. • Preti, Robert A.
Assignees
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Publication Number
US-8709403-B2
Publication Date
2014-04-29
Expiration Date
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 CD34+/CXCR-4+ cells having CXCR-4-mediated chemotactic activity, methods of preparing these compositions and use of these compositions to treat or repair vascular injury, including infarcted myocardium.
Core Innovation
The patent describes a sterile pharmaceutical composition for parenteral administration through a catheter. The composition includes a therapeutic amount of a sterile chemotactic hematopoietic stem cell product comprising a nonexpanded population of mononuclear cells enriched for CD34+ cells and containing a subpopulation of potent CD34+/CXCR-4+ cells that move in response to SDF-1, VEGF or both and have CXCR-4-mediated chemotactic activity.
The composition further includes a stabilizing amount of serum constituting about 0.1% to about 70% (v/v). The serum retains the CXCR-4-mediated chemotactic activity and hematopoietic colony forming activity of the CD34+/CXCR-4+ subpopulation that moves in response to SDF-1, VEGF or both, and the therapeutic amount comprises at least 0.5 × 10^6 potent SDF-1 mobile CD34+/CXCR-4+ cells effective to repair a vascular injury caused by vascular insufficiency in a subject in need thereof.
The composition is characterized by properties for at least 24 hours following acquisition of the mononuclear cells when tested in vitro after passage through the catheter. The composition has at least 70% CD34+ cells, at least 1% retention of chemotactic activity by the potent CD34+/CXCR-4+ subpopulation, at least 70% viable cells, and the CD34+ cells are able to form hematopoietic colonies in vitro.
Claims Coverage
The claims cover 3 inventive features centered on a sterile catheter-administered composition that preserves CXCR-4-mediated chemotactic function and hematopoietic colony forming activity of a nonexpanded, CD34+-enriched mononuclear cell product containing a potent CD34+/CXCR-4+ subpopulation.
Sterile catheter-administered chemotactic hematopoietic stem cell product enriched for potent CD34+/CXCR-4+ cells
A sterile pharmaceutical composition for parenteral administration through a catheter, comprising a therapeutic amount of a sterile chemotactic hematopoietic stem cell product that is a nonexpanded population of mononuclear cells enriched for CD34+ cells and containing a subpopulation of potent CD34+/CXCR-4+ cells that move in response to SDF-1 and/or VEGF and have CXCR-4-mediated chemotactic activity.
Serum stabilizing amount to retain CXCR-4 mediated chemotactic activity and hematopoietic colony forming activity
The composition includes a stabilizing amount of serum constituting about 0.1% to about 70% (v/v), effective to retain the CXCR-4 mediated chemotactic activity and hematopoietic colony forming activity of the CD34+/CXCR-4+ subpopulation that move in response to SDF-1, VEGF or both.
Post-catheter passage characterization for at least 24 hours with retained function
The composition is characterized by properties for at least 24 hours following acquisition of the mononuclear cells when tested in vitro after passage through the catheter, including at least 70% CD34+ cells, at least 1% retention of CXCR-4-mediated chemotactic activity by the potent CD34+/CXCR-4+ subpopulation, at least 70% viable cells, and the ability of CD34+ cells to form hematopoietic colonies in vitro.
Overall claim coverage centers on a sterile catheter-administered composition that preserves CXCR-4-mediated chemotactic function and hematopoietic colony forming activity of a nonexpanded, CD34+-enriched mononuclear cell product containing a potent CD34+/CXCR-4+ subpopulation.
Stated Advantages
Retains CXCR-4-mediated chemotactic activity after passage through the catheter for at least 24 hours.
Retains hematopoietic colony forming activity of the CD34+/CXCR-4+ subpopulation after catheter passage.
Has defined post-catheter preservation characteristics for at least 24 hours, including CD34+ enrichment, chemotactic activity retention, viability, and hematopoietic colony formation in vitro.
Repairs a vascular injury caused by vascular insufficiency.
Documented Applications
Repair of a vascular injury caused by vascular insufficiency in a subject in need thereof.
Intravascular infusion through a catheter, including administration to an infarct related artery (IRA) in connection with a balloon catheter and a four-way stopcock system.
Vascular insufficiency related to coronary artery occlusion and ischemia-related conditions.
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