Methods of cardiac repair

Abstract

Provided herein is a new method to isolate and expand cardiac progenitor / stem cells from a placenta, which produces a cell population enriched in multipotent functional progenitor / stem cells. Cardiac progenitor / stem cells isolated by this method maintain their self-renewal character in vitro and differentiate into normal cells in myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells, after transplantation into ischemic hearts. Also provided in this application are substantially pure populations of multipotent cardiac progenitor / stem cells, and their use to treat and prevent diseases and injuries, including those resulting from myocardial infarction. A model for assessing the potential of cardiac stem cells for treatment of myocardial infarction is also provided.

Description

CROSS-REFERENCE[0001]This application is a Continuation of U.S. application Ser. No. 13 / 671,396, filed Nov. 7, 2012, which claims the benefit of U.S. Provisional Application No. 61 / 556,700, filed Nov. 7, 2011, which application is incorporated herein by reference in its entirety.STATEMENT OF FEDERAL FUNDING[0002]Embodiments of the present application were made, in part, with U.S. government support under NHLBI (R01-HL 088255) awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Heart failure is the leading cause of hospitalization in the US and heart disease remains the number one killer in the industrialized world. Each year over 1.1 million Americans have a myocardial infarction (“MI”), typically caused by a heart attack, with median survival after onset only 1.7 years in men and 3.2 years in women. Typically, 225,000 people suffering MI die before reaching the hospital.[0004]Myocardial infarctions result...

AI Technical Summary

Benefits of technology

[0008]Provided herein is a composition comprising a population of cells and a pharmaceutically acceptable carrier for increasing cardiomyocyte formation, increase cardiomyocyte proliferation, increase cardiomyocyte cell cycle activation, increase mitotic index of cardiomyocytes, increase myofilament density, increase borderzone wall thickness, or a combination thereof, wherein said cells express one or more markers identified in Table 2 or in FIG. 5C. In one embodiment, the cells are derived from placenta. In another embodiment, the cells are progenitor cells or stem cells. In another embodiment, the cells express Cdx2, Cd9, Eomes, CD34, CD31, c-kit, or a combination thereof. In another embodiment, the cells express Cdx2 and Cd9.

[0018]In various embodiments, the cell population increases cardiomyocyte formation, increases cardiomyocyte proliferation, increases cardiomyocyte cell cycle activation, increases mitotic index of cardiomyocytes, increases myofilament density, increases borderzone wall thickness, or a combination thereof.

[0020]In one embodiment, the composition increases cardiomyocyte formation, increase cardiomyocyte proliferation, increase cardiomyocyte cell cycle activation, increase mitotic index of cardiomyocytes, increase myofilament density, increase borderzone wall thickness, or a combination thereof, when administered to a subject.

[0022]Provided herein is a composition including a population of Cdx2 cells and a pharmaceutically acceptable carrier for the preparation of a medicament to increase cardiomyocyte formation, increase cardiomyocyte proliferation, increase cardiomyocyte cell cycle activation, increase mitotic index of cardiomyocytes, increase myofilament density, increase borderzone wall thickness, or a combination thereof. In one embodiment, the cells are derived from placenta. In another embodiment, the cells are progenitor cells or stem cells. In another embodiment, the cells express Cdx2, and further express Cd9, Eomes, CD34, CD31, c-kit or a combination thereof. In another embodiment, the cells express Cdx2 and Cd9.

[0025]In one embodiment, the composition increases cardiomyocyte formation, increases cardiomyocyte proliferation, increases cardiomyocyte cell cycle activation, increases mitotic index of cardiomyocytes, increases myofilament density, increases borderzone wall thickness, or a combination thereof, when administered to a subject.

[0027]A composition including a population of Cdx2 cells and a pharmaceutically acceptable carrier to increase cardiomyocyte formation, increase cardiomyocyte proliferation, increase cardiomyocyte cell cycle activation, increase mitotic index of cardiomyocytes, increase myofilament density, increase borderzone wall thickness, or a combination thereof. In one embodiment, the cells are derived from placenta. In another embodiment, the cells are progenitor cells or stem cells. In another embodiment, the cells express Cdx2, and further express Cd9, Eomes, CD34, CD31, c-kit, or a combination thereof. In another embodiment, the cells express Cdx2 and Cd9.

Problems solved by technology

Myocardial infarctions result in an immediate depression in ventricular function and the infarctions may expand, thereby causing ventricular remodeling.

In many patients, progressive myocardial infarct expansion and ventricular remodeling leads to deterioration of ventricular function and heart failure.

Within seconds of a myocardial infarction, the under-perfused myocardial cells no longer contract, leading to abnormal wall motion, high wall stresses within and surrounding the infarct, and depressed ventricular function.

These high stresses eventually kill or severely depress function in the still viable myocardial cells.

The consequences of MI may be often severe and disabling.

Images