Abstract: The invention concerns a system for modulating tissue physiology, for example, to prevent or reverse tissue damage caused by disease. The system utilizes vigilant cells that include stable vectors containing a gene switch/biosensor and a gene amplification system. The vectors allow expression of a transgene (such as a cardioprotective gene) in the vigilant cells to be regulated in response to a physiological signal, to be switched on or off, and to provide sufficient levels of the transgene product to achieve a desired result, e.g., prevention or reversal of myocardial cell damage. In addition to myocardial infarction, the vectors can be used to treat cells in a number of other disease states, including diabetes, cancer, stroke, and atherosclerosis. These approaches to stem cell-based gene therapy provide a novel strategy not only for treatment but for prevention of cell destruction.

Abstract: The invention relates to methods and compositions for selectively directing stem cells to a target tissue within a subject using a system that employs one or more vectors that contain a gene switch/biosensor, a tissue-specific promoter, a gene encoding a stem cell-attracting chemokine, and a gene amplification system. In one embodiment, a stem cell-attracting chemokine is expressed in damaged tissue using a stimulus-responsive vector system. The stimulus can be a physiological stimulus associated with cell injury, such as hypoxia or elevated glucose levels, for example. Expression of the chemokine increases the trafficking of stem cells to the damaged tissue.

Abstract: The invention relates to methods and compositions for selectively directing stem cells to a target tissue within a subject using a system that employs one or more vectors that contain a gene switch/biosensor, a tissue-specific promoter, a gene encoding a stem cell-attracting chemokine, and a gene amplification system. In one embodiment, a stem cell-attracting chemokine is expressed in damaged tissue using a stimulus-responsive vector system. The stimulus can be a physiological stimulus associated with cell injury, such as hypoxia or elevated glucose levels, for example. Expression of the chemokine increases the trafficking of stem cells to the damaged tissue.

Abstract: The present invention provides a novel method to isolate and expand pure progenitor/stem cells from a primary tissue explant, which produces a population enriched in multipotent functional progenitor/stem cells free of contaminating fibroblasts and other cell types. Cardiac progenitor/stem cells isolated by this method maintain their self-renewal and clonogenic character in vitro and differentiate into normal cells in myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells, after transplantation into ischemic hearts. The present invention also includes substantially pure populations of multipotent progenitor/stem cells, e.g., cardiac progenitor/stem cells, and their use to treat and prevent diseases and injuries, including those resulting from myocardial infarction.

Abstract: The present invention provides a novel method to isolate and expand pure progenitor/stem cells from a primary tissue explant, which produces a population enriched in multipotent functional progenitor/stem cells free of contaminating fibroblasts and other cell types. Cardiac progenitor/stem cells isolated by this method maintain their self-renewal and clonogenic character in vitro and differentiate into normal cells in myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells, after transplantation into ischemic hearts. The present invention also includes substantially pure populations of multipotent progenitor/stem cells, e.g., cardiac progenitor/stem cells, and their use to treat and prevent diseases and injuries, including those resulting from myocardial infarction.

Abstract: The present invention provides a novel method to isolate and expand pure progenitor/stem cells from a primary tissue explant, which produces a population enriched in multipotent functional progenitor/stem cells free of contaminating fibroblasts and other cell types. Cardiac progenitor/stem cells isolated by this method maintain their self-renewal and clonogenic character in vitro and differentiate into normal cells in myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells, after transplantation into ischemic hearts. The present invention also includes substantially pure populations of multipotent progenitor/stem cells, e.g., cardiac progenitor/stem cells, and their use to treat and prevent diseases and injuries, including those resulting from myocardial infarction.