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Assignees
Member
Icahn School of Medicine at Mount SinaiThe Icahn School of Medicine at Mount Sinai, located in New York City, is an international leader in biomedical education, research, and patient care. As the academic partner of the Mount Sinai Health System, the school is renowned for its innovative education, groundbreaking research, and commitment to health equity. With over 7,000 faculty, 1,200 students, and 2,500 residents and fellows, the institution fosters a culture of bold thinking, multidisciplinary teamwork, and a willingness to challenge conventional wisdom. Its mission is to radically advance the art and science of medical care through collaborative learning, scholarly inquiry, and a deep respect for diversity, preparing the next generation of healthcare leaders to revolutionize medicine and biomedical science.
The Icahn School of Medicine at Mount Sinai, located in New York City, is an international leader in biomedical education, research, and patient care. As the academic partner of the Mount Sinai Health System, the school is renowned for its innovative education, groundbreaking research, and commitment to health equity. With over 7,000 faculty, 1,200 students, and 2,500 residents and fellows, the institution fosters a culture of bold thinking, multidisciplinary teamwork, and a willingness to challenge conventional wisdom. Its mission is to radically advance the art and science of medical care through collaborative learning, scholarly inquiry, and a deep respect for diversity, preparing the next generation of healthcare leaders to revolutionize medicine and biomedical science.
Publication Number
US-11963983-B2
Publication Date
2024-04-23
Expiration Date
2032-11-07
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.
Core Innovation
The invention provides a novel method to isolate and expand cardiac progenitor or stem cells from placenta, yielding a population enriched in multipotent functional progenitor or stem cells. These cardiac progenitor or stem cells maintain self-renewal in vitro and can differentiate into cardiomyocytes, endothelial cells, and smooth muscle cells after transplantation into ischemic hearts, facilitating cardiac repair and regeneration.
The disclosed compositions comprise cells derived from placenta that express markers including Cdx2, Cd9, Eomes, CD34, CD31, and c-kit, with particular emphasis on cells expressing Cdx2 and Cd9. The compositions, administered with pharmaceutically acceptable carriers, increase cardiomyocyte formation, proliferation, cell cycle activation, mitotic index, myofilament density, and borderzone wall thickness, thus enhancing cardiac regeneration and function.
The invention addresses the problem posed by myocardial infarction, which causes ventricular dysfunction, remodeling, and heart failure due to myocardial tissue death and scarring. Existing cardiac progenitor populations are insufficient for restoring cardiac function, and embryonic stem cells pose ethical and safety concerns. This invention provides an alternative cell source, placenta-derived progenitor/stem cells marked by Cdx2, capable of homing selectively to injured myocardium, differentiating into diverse cardiac lineages, and restoring cardiac function in vivo and in vitro.
Claims Coverage
The patent claims focus on a method for restoring cardiac function using a composition of placenta-derived cells characterized by Cdx2 expression and related features. There are twelve inventive features extracted from the independent claims.
Method of restoring cardiac function using placenta-derived Cdx2-expressing cells
Introducing an effective amount of a composition comprising a population of placenta-derived cells into the heart of a subject in need thereof with at least about 75% of cells expressing caudal type homeobox 2 (Cdx2).
Use of progenitor or stem cells
The placenta-derived cells used in the method are progenitor cells or stem cells.
Expression of additional stem cell markers
The cells express one or more of cluster of differentiation (Cd9), Eomesodermin (Eomes), CD34, CD31, and c-kit.
Functional cardiac improvements achieved by the composition
The composition increases cardiomyocyte formation, proliferation, cell cycle activation, mitotic index, myofilament density, borderzone wall thickness, or any combination thereof.
Fetal origin of Cdx2-expressing cells
The Cdx2-expressing cells are fetal stem cells.
Purity of Cdx2-expressing cells
The Cdx2-expressing cells are isolated cells.
Treatment of subjects with cardiac conditions or risks
The subject is diagnosed with, or at risk for, myocardial infarction, chronic coronary ischemia, arteriosclerosis, congestive heart failure, dilated cardiomyopathy, restenosis, coronary artery disease, heart failure, arrhythmia, angina, atherosclerosis, hypertension, or myocardial hypertrophy.
Modes of delivering composition by implantation
Introducing or contacting the composition comprises implanting the composition into cardiac tissue of the subject.
Modes of delivering composition by injection
Introducing or contacting the composition comprises injecting the composition into the subject.
Target cardiac tissue for implantation
The cardiac tissue includes myocardium, endocardium, epicardium, connective tissue in the heart, and nervous tissue in the heart.
Dosage range—higher cell counts
The amount of composition comprises from about 1×108 to about 1×102 cells.
Dosage range—lower cell counts
The amount of introduced composition comprises from about 1×106 to about 1×105 cells.
The claims cover a method of cardiac repair using isolated placenta-derived cell populations enriched in Cdx2-expressing progenitor or stem cells, which express markers including Cd9, Eomes, CD34, CD31, and c-kit. The method encompasses administering an effective amount of these cells to subjects diagnosed with or at risk for various cardiac conditions, employing implantation or injection modes, in dosages ranging from about 1×102 to 1×108 cells, achieving improvements in cardiomyocyte regeneration and cardiac function.
Stated Advantages
Isolation of cells from placenta provides an ethical and readily available source avoiding issues with embryonic stem cells.
Fetal cells selectively home to injured maternal hearts and differentiate into diverse cardiac lineages, including functional beating cardiomyocytes.
The method increases cardiomyocyte formation, proliferation, cell cycle activation, mitotic index, myofilament density, and tissue thickness, enhancing cardiac repair.
Use of Cdx2-positive cells offers a new therapeutic cell type for cardiovascular regenerative therapy capable of cardiac differentiation.
Documented Applications
Treatment and prevention of myocardial infarction, chronic coronary ischemia, arteriosclerosis, congestive heart failure, dilated cardiomyopathy, restenosis, coronary artery disease, heart failure, arrhythmia, angina, atherosclerosis, hypertension, or myocardial hypertrophy.
Use of a mouse model for assessing the role of fetal cells in treatment of cardiac injury post-myocardial infarction.
Implantation or injection delivery of placenta-derived progenitor or stem cell compositions for cardiac repair and regeneration in subjects diagnosed with, or at risk for, cardiac disease.
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