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Compositions comprising vascular and myocyte progenitor cells and methods of their use

a technology of myocyte progenitor cells and vascular progenitor cells, which is applied in the field of compositions of cardiac progenitor cells or cardiac stem cells, can solve the problems of severely impaired extent and regulation of myocardial perfusion, defective coronary vasculature, etc., and achieves the restoration of structural and functional integrity of damaged myocardium, increasing contractile function, and increasing blood flow to damaged myocardium

Inactive Publication Date: 2009-06-11
NEW YORK MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]The present invention also encompasses a method for restoring structural and functional integrity to damaged myocardium in a subject in need thereof. In one embodiment, the method comprises obtaining myocardial tissue from the subject; extracting vascular progenitor cells from said myocardial tissue; expanding said vascular progenitor cells in culture; and administering said vascular progenitor cells to the damaged myocardium, wherein the vascular progenitor cells differentiate into endothelial cells and smooth muscles cells forming functional coronary vessels, thereby increasing blood flow to the damaged myocardium. In another embodiment, the method further comprises extracting myocyte progenitor cells from said myocardial tissue, expanding said myocyte progenitor cells in culture; and administering said myocyte progenitor cells to the damaged myocardium, wherein the myocyte progenitor cells differentiate into cardiomyocytes forming functional myocardium, thereby increasing contractile function. The myocyte progenitor cells may be administered simultaneously with the vascular progenitor cells or after a particular time interval.
[0009]The present invention also provides a method for treating or preventing hypertensive cardiomyopathy in a subject in need thereof comprising administering a pharmaceutical composition comprising vascular progenitor cells and myocyte progenitor cells to the subject's heart, wherein the vascular progenitor cells and myocyte progenitor cells engraft in said subject's heart, thereby repopulating diminished progenitor cell niches or forming new progenitor cell niches. In one embodiment, the vascular progenitor cells and myocyte progenitor cells are autologous. In another embodiment, the probability of the subject having heart failure is reduced following administration of the pharmaceutical composition.
[0010]The present invention includes a method for treating or preventing heart failure in a subject in need thereof. In one embodiment, the method comprises obtaining myocardial tissue from the subject; extracting vascular progenitor cells from said myocardial tissue; expanding said vascular progenitor cells in culture; and administering said vascular progenitor cells to the subject's heart, wherein the vascular progenitor cells differentiate into endothelial cells and smooth muscles cells forming functional coronary vessels, thereby increasing cardiac function. In another embodiment, the method further comprises extracting myocyte progenitor cells from said myocardial tissue, expanding said myocyte progenitor cells in culture; and administering said myocyte progenitor cells to the damaged myocardium, wherein the myocyte progenitor cells differentiate into cardiomyocytes forming functional myocardium, thereby increasing cardiac function.

Problems solved by technology

In addition to the loss in muscle mass, the coronary vasculature remains defective and the extent and regulation of myocardial perfusion are severely impaired (271-281).

Method used

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  • Compositions comprising vascular and myocyte progenitor cells and methods of their use
  • Compositions comprising vascular and myocyte progenitor cells and methods of their use
  • Compositions comprising vascular and myocyte progenitor cells and methods of their use

Examples

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example 1

Identification of VPCs and Vascular Niches in the Mouse Heart

[0096]The objective of the experiments outlined in this example is to identify and characterize vascular niches containing vascular progenitor cells within the vasculature of murine hearts. Homozygous c-kit-EGFP mice at 4 months are used for this study (182). They were generated through microinjection of FVB / NJ 0.5 dpc zygotes with clone 2 of the c-kit-EGFP construct. Founder animals were genotyped by PCR and backcrossed to stabilize the transgene. High expressing lines were characterized by PCR and immunohistochemistry for colocalization of endogenous c-kit and EGFP; testes, heart and bone marrow were examined. Although EGFP is under the control of the c-kit promoter, mice do not develop a dilated myopathy. Cardiac function and anatomy were measured in a group of 28 male homozygous mice at 6-11 months of age. No significant differences between wild-type and c-kit-EGFP mice were observed in left ventricular (LV) anatomy or...

example 2

Restoration of Vascular and Myocyte Niches may Reverse Heart Failure

[0118]Heart failure may be a stem cell disease. The alteration in coronary perfusion and muscle contractile behavior of the decompensated heart may result from depletion of functional VPCs and MPCs which become unable to form a number of vascular cells and cardiomyocytes required to counteract the abnormal hemodynamic load. Although multiple variables including defects in hormonal regulation, calcium metabolism, contractile regulatory proteins, and complex signal transduction pathways with upregulation or downregulation of a variety of gene products have been recognized, the initial triggering event of heart failure remains obscure (157, 236, 237).

[0119]Pressure loading induces concentric ventricular hypertrophy, in which wall thickness increases without chamber enlargement (148, 238-240). In its compensated form, mural thickening is the result of an increase in myocyte diameter and / or myocyte number in the absence ...

example 3

Identification and Characterization of VPCs and MPCs in Dogs

[0134]There are several aims of this Example: (a) To demonstrate that the normal canine heart contains a population of lineage negative c-kit-positive flk1-positive cells, i.e., VPCs, which are located in the intima, media and adventitia of the coronary vasculature including the capillary network; (b) To demonstrate that VPCs are located in vascular niches present in the various segments of the dog coronary circulation; (c) To demonstrate that VPCs can be isolated and expanded from adult dog epicardial coronary arteries and small samples of atrial and ventricular myocardium; (d) To demonstrate that VPCs possess the properties of stem cells and differentiate into ECs and SMCs and only to a limited extent into myocytes; (e) To demonstrate that the canine heart contains a population of lineage negative c-kit-positive flk1-negative cells, i.e., MPCs, which are located in myocardial niches; (f) To demonstrate that MPCs can be is...

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Abstract

The invention provides compositions of adult cardiac vascular progenitor cells (VPCs) and adult cardiac myocyte progenitor cells (MPCs) useful for the treatment of various cardiac conditions. The invention also encompasses methods of generating a biological bypass, repairing damaged myocardium, and treating or preventing hypertensive cardiomyopathy and heart failure with the compositions of the invention. Methods of isolating the cardiac progenitor cells are also disclosed.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 60 / 991,515, filed Nov. 30, 2007, which is herein incorporated by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates generally to the field of cardiology, and more particularly relates to compositions of cardiac progenitor cells or cardiac stem cells and methods of using the compositions for repairing damaged myocardium and / or generating a biological coronary bypass.BACKGROUND OF THE INVENTION[0003]Acute and chronic post-infarction ischemic heart failure in humans is characterized by myocardial regeneration which is limited to the myocyte compartment of the surviving myocardium (259-270). Additionally, small areas of spontaneous myocardial regeneration which invade the infarct shortly after the ischemic event have been identified (267). In addition to the loss in muscle mass, the coronary vasculature remains defective and the extent and...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/34A61P9/00A61K35/12
CPCC12N5/0692A61K35/12A61P9/00A61P9/10
Inventor ANVERSA, PIEROLERI, ANNAROSAKAJSTURA, JAN
Owner NEW YORK MEDICAL COLLEGE
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