Genetically altered mammalian embryonic stem cells, their living progeny, and their therapeutic application for improving cardiac function after myocardial infarction
First Claim
1. A method for improving cardiac function in a mammal after a myocardial infarct, said method comprising the steps of:
- maintaining a plurality of undifferentiated, genetically altered mammalian embryonic stem cells in vitro in a culture medium containing at least one selected from the group consisting of leukemia inhibitory factor and fibroblast feeder cells;
said undifferentiated, genetically altered mammalian embryonic stem cells comprising;
a mammalian embryonic stem cell which (i) remains uncommitted and undifferentiated while passed in vitro, (ii) is implantable in vivo at a chosen anatomic site as an uncommitted cell, and (iii) engrafts in situ after implantation in a mammal at a local anatomic site, and, (iv) contains a vector comprising a DNA sequence operably linked to a promoter, wherein the DNA sequence encodes an angiogenic factor which is expressed in situ;
subsequently culturing said undifferentiated, genetically altered mammalian embryonic stem cells for a predetermined time in a culture media in the absence of leukemia inhibitory factor and fibroblast feeder cells to yield a cellular inoculum comprising mammalian cells in which differentiation has been initiated;
introducing said cellular inoculum to at least a portion of the previously infarcted area of the heart tissue; and
allowing said introduced cellular inoculum to engraft in situ as viable cells situated within the previously infarcted area of the heart tissue, wherein the engraftment results in improved cardiac function in said mammal.
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Abstract
The present invention provides genetically altered mammalian embryonic stem cells, their living descendent progeny having an altered genomic DNA, and therapeutic methods using these cells for improving cardiac function in a living subject after myocardial infarction. The genetically altered embryonic stem and progenitor cells may be maintained in-vitro as a stable cell line; and transplanted as active, mitotic cells to an infarcted area of the myocardial using any surgical procedure. After transplantation at a chosen anatomic site within the heart of the subject, these genetically altered cells will differentiate in-site, cause a regeneration of myocardocytes, and will effect a marked improvement in cardiac function for the subject.
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Citations
5 Claims
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1. A method for improving cardiac function in a mammal after a myocardial infarct, said method comprising the steps of:
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maintaining a plurality of undifferentiated, genetically altered mammalian embryonic stem cells in vitro in a culture medium containing at least one selected from the group consisting of leukemia inhibitory factor and fibroblast feeder cells;
said undifferentiated, genetically altered mammalian embryonic stem cells comprising;
a mammalian embryonic stem cell which (i) remains uncommitted and undifferentiated while passed in vitro, (ii) is implantable in vivo at a chosen anatomic site as an uncommitted cell, and (iii) engrafts in situ after implantation in a mammal at a local anatomic site, and, (iv) contains a vector comprising a DNA sequence operably linked to a promoter, wherein the DNA sequence encodes an angiogenic factor which is expressed in situ;
subsequently culturing said undifferentiated, genetically altered mammalian embryonic stem cells for a predetermined time in a culture media in the absence of leukemia inhibitory factor and fibroblast feeder cells to yield a cellular inoculum comprising mammalian cells in which differentiation has been initiated;
introducing said cellular inoculum to at least a portion of the previously infarcted area of the heart tissue; and
allowing said introduced cellular inoculum to engraft in situ as viable cells situated within the previously infarcted area of the heart tissue, wherein the engraftment results in improved cardiac function in said mammal. - View Dependent Claims (3, 4, 5)
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2. A method for improving cardiac function in a mammal after a myocardial infarct, said method comprising the steps of:
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obtaining a plurality of progeny cells of undifferentiated, genetically altered mammalian embryonic stem cells, maintaining said undifferentiated, genetically altered progeny cells in vitro in a culture medium containing at least one selected from the group consisting of leukemia inhibitory factor and fibroblast feeder cells, said undifferentiated, genetically altered progeny cells comprising;
progeny cells of mammalian embryonic stem cells which (i) remain undifferentiated while passed in vitro, (ii) are implantable in vivo at a chosen anatomic site as viable cells, (iii) engraft in situ after implantation in a mammal at a local anatomic site, and, (iv) contain a vector comprising a DNA sequence operably linked to a promoter, wherein the DNA sequence encodes an angiogenic factor, which is expressed in situ;
subsequently culturing said undifferentiated, genetically altered progeny cells for a predetermined time in a culture media in the absence of leukemia inhibitory factor and fibroblast feeder cells to yield a cellular inoculum comprising mammalian cells in which differentiation has been initiated;
introducing said cellular inoculum to at least a portion of the previously infarcted area of the heart tissue; and
allowing said introduced cellular inoculum to engraft in situ as viable cells situated within the previously infarcted area of the heart tissue, wherein the engraftment results in improved cardiac function in said mammal.
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Specification