Abstract: A method of delivering an oligonucleotide or a plasmid expressing an oligonucleotide into a target cell comprises introducing an oligonucleotide into a donor cell, particularly a stem cell, and contacting the target cell with the donor cell under conditions permitting the donor cell to form a gap junction with the target cell, whereby the oligonucleotide or a product of the oligonucleotide is delivered into the target cell from the donor cell.

Abstract: The present invention provides methods and compositions relating to the production of stem cells, derived from dedifferentiated fibroblasts, and the use of such stem cells for treatment of a variety of different disorders and conditions. The invention is based on the surprising discovery that a population of stem cells, capable of differentiating into a variety of different cell types, can be generated by culturing fibroblasts under selective culture conditions.

Abstract: The present invention relates to methods and compositions for stimulating the proliferation of cardiomyocytes for enhancement of cardiac repair. The invention is based on the discovery that upon contact with stem cells, or conditioned media derived from said stem cells, terminally differentiated cardiomyocytes can be stimulated to enter the cell cycle. Additionally, scaffolds capable of attracting stem cells to the area of implantation have been shown to induce cardiomyocyte proliferation. The present invention further relates to the discovery that the Wnt-5A ligand, which binds to the frizzled receptor (fz), functions to stimulate cardiomyocyte proliferation. The methods and compositions of the invention may be used in the treatment of cardiac disorders including, but not limited to, myocardial dysfunction or infarction.

Abstract: A method of delivering an oligonucleotide or a plasmid expressing an oligonucleotide into a target cell comprises introducing an oligonucleotide into a donor cell, particularly a stem cell, and contacting the target cell with the donor cell under conditions permitting the donor cell to form a gap junction with the target cell, whereby the oligonucleotide or a product of the oligonucleotide is delivered into the target cell from the donor cell.

Abstract: This invention provides a composition for delivery of a gene to a syncytial structure comprising stem cells incorporated with the gene. This invention also provides a composition for ion channel transfer which comprises stem cells incorporated with a compound in an amount sufficient to create ion channels. This invention also provides for a method of expressing a functional gene product in a syncytial structure comprising administering a composition, comprising stem cells that have been incorporated with a gene, to the syncytial structure. This invention further provides a method of expressing a functional ion channel in a syncytial structure comprising administering a composition, comprising stem cells that have been incorporated with a compound in an amount sufficient to create ion channels, to the syncytial structure. This invention also provides a composition for delivery of small molecules comprising stem cells incorporated with the small molecules or genes encoding the small molecules.

Abstract: The present invention provides compositions and methods of treatment for atrial fibrillation and ventricular tachycardia. The compositions are useful for modifying the conducting properties of heart tissues in which impulses are generating and/or are useful for altering refractoriness without prolonging repolarization.

Abstract: The present invention provides methods and compositions relating to the labeling of target cells with quantum dots (QDs). Specifically, a delivery system is disclosed based on the use of negatively charged QDs for delivery of a tracking fluorescent signal into the cytosol of target cells via a passive endocytosis-mediated delivery process. In a specific embodiment of the invention the target cell is a stem cell, preferably a mesenchymal stem cell (MSC). Such labeled MSCs provide a means for tracking the distribution and fate of MSCs that have been administered to a subject to promote cardiac repair. The invention is based on the discovery that MSCs can be tracked in vitro for up to at least 6 weeks. Additionally, QDs delivered in vivo can be tracked for up to at least 8 weeks, thereby permitting for the first time, the complete 3-D reconstruction of the locations of all MSCs following administration into a host.

Abstract: A device and method for analyzing cells includes a housing with a chamber, a barrier supported by a frame disposed within the chamber, and a plate arranged at a bottom surface of the housing interior of the chamber. The plate is adapted to receive and sustain cells and the barrier separates the plate into at least two contiguous separate areas. In some embodiments, a thin rubber strip is arranged at the bottom edge of the barrier, which facilitates control of the area in which each cell type is grown, the size of the gap between the cells, and helps prevents over growth of the two cell types on to each other.

Abstract: This invention provides methods for determining the ability of a gene construct to alter the rhythm and contractility of a syncytial cell. Furthermore, this invention provides methods for constructing a gene construct capable of altering the rhythm or contractility of a syncytial cell. Finally, this invention provides a method for constructing a gene construct capable of coupling to a syncytial cell.

Abstract: The present invention provides methods and compositions relating to the use of late passage mesenchymal stem cells (MSCs) for treatment of cardiac rhythm disorders. The late passage MSCs of the invention may be used to provide biological pacemaker activity and/or provide a bypass bridge in the heart of a subject afflicted with a cardiac rhythm disorder. The biological pacemaker activity and/or bypass bridge may be provided to the subject either alone or in tandem with an electronic pacemaker.

Abstract: The present invention provides methods and compositions relating to the use of late passage mesenchymal stem cells (MSCs) for treatment of cardiac disorders. Such late passage MSCs may be administered to the myocardium of a subject for induction of native cardiomyoctye proliferation and repair of cardiac tissue. Additionally, the late passage MSCs may be genetically engineered to express a gene encoding a physiologically active protein of interest and/or may be incorporated with small molecules for delivery to adjacent target cells through gap junctions. The late passage MSCs of the invention may be used to provide biological pacemaker activity and/or provide a bypass bridge in the heart of a subject afflicted with a cardiac rhythm disorder. The biological pacemaker activity and/or bypass bridge may be provided to the subject either alone or in tandem with an electronic pacemaker.

Abstract: The present invention provides methods and compositions relating to the labeling of target cells with nanometer scale fluorescent semiconductors referred to as quantum dots (QDs). Specifically, a delivery system is disclosed based on the use of negatively charged QDs for delivery of a tracking fluorescent signal into the cytosol of target cells via a passive endocytosis-mediated delivery process. In a specific embodiment of the invention the target cell is a stem cell, preferably a mesenchymal stem cell (MSC). Such labeled MSCs provide a means for tracking the distribution and fate of MSCs that have been genetically engineered to express, for example, a hyperpolarization-activated cyclic nucleotide-gated (“HCN”) channel and administered to a subject to create a biological pacemaker. The invention is based on the discovery that MSCs can be tracked in vitro for up to at least 6 weeks.

Abstract: This invention provides pacemaker systems comprising (1) an electronic pacemaker, and (2) a biological pacemaker, wherein the biological pacemaker comprises a cell that functionally expresses a chimeric hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channel at a level effective to induce pacemaker current in the cell. The invention also provides related biological pacemakers, atrioventricular bridges, methods of making same, and methods of treating a subject afflicted with a cardiac rhythm disorder.

Abstract: A method of creating an atrioventricular bypass tract for a heart comprises growing mesenchymal stem cells into a strip with two ends, attaching one end of the strip onto the atrium of the heart, and attaching the other end of the strip to the ventricle of the heart, to create a tract connecting the atrium to the ventricle to provide a path for electrical signals generated by the sinus node to propagate across the tract and excite the ventricle.

Abstract: This invention provides for a chamber and system designed for use in assaying drug effects on heart rate. The chamber consists of a series of wells. Cardiac myocytes disaggregated from neonatal animals are plated onto the bottom of each well and grown under standard tissue culture conditions. When drugs are to be assayed, the cells in each well are loaded with a calcium sensitive dye and the beating rate in each is monitored with a photodiode. A drug is added in graded concentrations to each well, and equilibrated and effects on rate are observed. This construct permits use of a cell based bioassay for the study of drugs or agents that may alter cardiac rate. This invention can be used in high throughput screening of drugs to evaluate/predict their effects on cardiac rate and rhythm.

Abstract: The invention provides a method of treating a heart to remodel gap junctions, obtain gap junctional remodeling and/or alteration or effective refractory period comprising contacting linked multiple electrode pairs to an epicardial surface of a heart, and connecting the electrode pairs to a pacemaker to apply periodic electrical signals to the epicardial surface through the electrode pairs, the signals being applied for a sufficient time and having characteristics sufficient to remodel gap junctions, obtain gap junctional remodeling and/or alteration of effective refractory period in the heart. The invention also provides a device comprising a strip of electrode material having mounted thereon linked multiple electrode pairs arranged in two columns.

Abstract: This invention provides for a method of inducing a current in the heart in a subject which comprises contacting a cell of the heart of a subject with a compound in a sufficient amount to induce a current in the cell of the heart of a subject. This invention also provides a method of treating a cardiac condition in a subject which comprises contacting a cell of the heart of the subject with a compound in an amount sufficient to increase the current expression of the cell, thereby treating the cardiac condition in the subject.

Abstract: This invention provides for a chamber and system designed for use in assaying drug effects on heart rate. The chamber consists of a series of wells, each 3 mm by 3 mm in inner diameter. Cardiac myocytes disaggregated from neonatal animals are plated onto the bottom of each well and grown under standard tissue culture conditions. The chamber holds from 24-96 such wells. When drugs are to be assayed, the cells in each well are loaded with a calcium sensitive dye and the beating rate in each is monitored with a photodiode. Drug is added in graded concentrations to each well, and equilibrated and effects on rate are observed. This construct permits use of a cell based bioassay for the study of drugs or agents that may alter cardiac rate. This invention can be used in high throughput screening of drugs to evaluate/predict their effects on cardiac rate and rhythm. Further provided for by this invention is a vector which comprises a compound which encodes an ion channel.

Abstract: This invention provides a composition for delivery of a gene to a syncytial structure comprising stem cells incorporated with the gene. This invention also provides a composition for ion channel transfer which comprises stem cells incorporated with a compound in an amount sufficient to create ion channels. This invention also provides for a method of expressing a functional gene product in a syncytial structure comprising administering a composition, comprising stem cells that have been incorporated with a gene, to the syncytial structure. This invention further provides a method of expressing a functional ion channel in a syncytial structure comprising administering a composition, comprising stem cells that have been incorporated with a compound in an amount sufficient to create ion channels, to the syncytial structure. This invention also provides a composition for delivery of small molecules comprising stem cells incorporated with the small molecules or genes encoding the small molecules.

Abstract: This invention provides for a chamber and system designed for use in assaying drug effects on heart rate. The chamber consists of a series of wells, each 3 mm by 3 mm in inner diameter. Cardiac myocytes disaggregated from neonatal animals are plated onto the bottom of each well and grown under standard tissue culture conditions. The chamber holds from 24-96 such wells. When drugs are to be assayed, the cells in each well are loaded with a calcium sensitive dye and the beating rate in each is monitored with a photodiode. Drug is added in graded concentrations to each well, and equilibrated and effects on rate are observed. This construct permits use of a cell based bioassay for the study of drugs or agents that may alter cardiac rate. This invention can be used in high throughput screening of drugs to evaluate/predict their effects on cardiac rate and rhythm. Further provided for by this invention is a A vector which comprises a compound which encode an ion channel.