Infarct area perfusion-improving compositions and methods of vascular injury repair
Inventors
Pecora, Andrew • Preti, Robert
Assignees
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Publication Number
US-9034316-B2
Publication Date
2015-05-19
Expiration Date
Abstract
The described invention provides pharmaceutical compositions for treating an infarct area injury and methods of treating or repairing the infarct area injury in a revascularized subject in the aftermath of an acute myocardial infarction resulting from a natural disease process by administering to the subject parenterally through a catheter a sterile pharmaceutical composition containing a therapeutically effective amount of a nonexpanded sterile isolated chemotactic hematopoietic stem cell product as a first therapeutic agent and optionally a therapeutically effective amount of at least one compatible second therapeutic agent. The infarct area-improving amount of the sterile isolated chemotactic hematopoietic stem cell product comprises an enriched population of isolated autologous CD34+ cells containing a subpopulation of potent cells expressing CXCR-4 and having CXCR-4-mediated chemotactic activity such that the enriched population of isolated autologous CD34+ hematopoietic stem cells provides at least 0.5×106 potent CD34+ cells expressing CXCR-4 and having CXCR-4 mediated chemotactic activity.
Core Innovation
A method is provided for treating adverse ventricular remodeling due to an infarct area injury resulting from acute myocardial infarction. The method acquires from a subject that has suffered an acute myocardial infarction an isolated population of autologous mononuclear cells comprising CD34+ cells, and the isolated population is sterilely enriched for CD34+ cells without expanding cell number in vitro so that at least 70% of the cells comprise CD34+ cells.
At least 24 hours after acquiring the isolated autologous mononuclear cells, a first portion of the enriched population is passed through a catheter, with in vitro confirmation that at least some of the passed cells have CXCR-4-mediated chemotactic activity and move in response to SDF-1, that at least 70% of the cells passed through the catheter are viable, and that at least some of the passed cells can form hematopoietic colonies in vitro.
A sterile pharmaceutical composition is then formulated for parenteral delivery through the catheter. The composition comprises a therapeutic amount of a sterile isolated chemotactic hematopoietic stem cell product that includes a second portion of the enriched population comprising at least 0.5×10^6 potent CD34+/CXCR-4+ cells expressing CXCR-4 and having CXCR-4 mediated chemotactic activity that move in response to SDF-1, and includes a stabilizing amount of serum effective to retain the CXCR-4 mediated chemotactic activity and hematopoietic colony forming activity of the CD34+/CXCR-4+ subpopulation that moves in response to SDF-1.
The sterile pharmaceutical composition is administered parenterally through the catheter at one or more infusion dates to treat adverse ventricular remodeling. The therapeutic amount is stated to reduce cardiomyocyte cell death by improving perfusion, to reduce cardiomyocyte apoptosis, and to preserve existing cardiomyocytes and cardiomyocyte function in the infarct area.
Claims Coverage
The patent includes one independent claim directed to a catheter-based, sterile pharmaceutical composition and parenteral administration method for adverse ventricular remodeling after acute myocardial infarction. The claim centers on sterile enrichment without in vitro expansion, catheter passage with in vitro confirmation of CXCR-4/SDF-1 chemotaxis, viability, and colony-forming capability, and formulation with a stabilizing serum and an effective chemotactic CD34+/CXCR-4+ subpopulation.
Sterile enrichment of autologous mononuclear CD34+ cells without in vitro expansion
Sterilely enriching an isolated population of autologous mononuclear cells for CD34+ cells without expanding cell number in vitro, so that at least 70% of the cells comprise CD34+ cells.
Catheter passage with in vitro confirmation of CXCR-4-mediated chemotaxis, viability, and colony formation
Passing a first portion of the enriched population through a catheter at least 24 hours after enrichment, and confirming in vitro CXCR-4-mediated chemotactic activity in response to SDF-1, at least 70% viability, and the ability to form hematopoietic colonies.
Sterile pharmaceutical composition with potent chemotactic CD34+/CXCR-4+ subpopulation
Formulating for parenteral delivery through the catheter a sterile pharmaceutical composition comprising a therapeutic amount of a sterile isolated chemotactic hematopoietic stem cell product that includes at least 0.5×10^6 potent CD34+ cells expressing CXCR-4 with CXCR-4 mediated chemotactic activity and movement in response to SDF-1.
Stabilizing serum retaining CXCR-4 chemotaxis and hematopoietic colony forming activity
Including a stabilizing amount of serum effective to retain CXCR-4 mediated chemotactic activity and hematopoietic colony forming activity of the CD34+/CXCR-4+ subpopulation that responds to SDF-1.
Optional compatible therapeutic agent
Including at least one compatible therapeutic agent selected from diuretic, anti-arrhythmic agent, anti-anginal agent, cytokine, tyrosine kinase receptor agonist, vasoactive agent, anticoagulant agent, fibrinolytic agent, hypercholesterolemic agent, or a combination thereof.
Parenteral catheter administration to treat adverse ventricular remodeling
Administering the sterile pharmaceutical composition parenterally through the catheter to treat adverse ventricular remodeling at one or more infusion dates.
Overall, the claim combines sterile enrichment, catheter passage with in vitro verification of CXCR-4-mediated SDF-1 chemotaxis and cell quality, formulation of a sterile chemotactic CD34+/CXCR-4+ product with stabilizing serum, and parenteral catheter administration to treat adverse ventricular remodeling.
Stated Advantages
Reduce cardiomyocyte cell death by improving perfusion in the infarct area.
Reduce cardiomyocyte apoptosis.
Preserve existing cardiomyocytes and cardiomyocyte function in the infarct area.
Documented Applications
Treating adverse ventricular remodeling due to infarct area injury resulting from acute myocardial infarction in a revascularized acute myocardial infarction subject, using catheter-based parenteral administration at one or more infusion dates.
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