摘要:
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.
摘要:
A method for treating a subject afflicted with a cardiac disorder, in vivo, comprising (i) producing a solution comprising media conditioned from the culture of cells, in vitro, and (ii) administering the solution of step (i) to the subject, thereby treating the cardiac disorder in the subject. Methods for determining whether an agent stimulates or inhibits myocyte proliferation.
摘要:
A method for treating a subject afflicted with a cardiac disorder, in vivo, comprises (i) inducing differentiation of a progenitor cell, in vitro, to a cardiogenic cell; and (ii) administering a therapeutically effective amount of the cardiogenic cell of step (i) to the subject, thereby treating the cardiac disorder in the subject. This invention further provides related articles of manufacture and methods.
摘要:
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.
摘要:
This invention provides a chimeric hyperpolarization-activated, cyclic nucleotide-gated (HCN) polypeptide comprising portions of more than one type of HCN channel. The invention also provides methods of treating a subject afflicted with a cardiac rhythm disorder comprising expression of the chimeric HCN polypeptide in a selected region of the heart so as to induce a pacemaker current in the heart and thereby treat the subject.
摘要:
This invention provides a bypass bridge comprising a tract of gap junction-coupled cells having a first end and a second end, both ends capable of being attached to two selected sites in a heart so as to allow the conduction of a pacemaker and/or electrical signal/current across the tract between the two sites, wherein the cells functionally express a sodium channel. The invention also provides related methods of making the bypass bridge, methods of implanting same in a heart, and methods of treating a disorder associated with an impaired conduction in a subject's heart.
摘要:
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.
摘要:
The invention provides a method for determining the effects of an agent on repolarization of cells in vitro, comprising stimulating the cells with an energy source and under conditions sufficient and for a time sufficient to depolarize the cells, measuring the QT interval of the electrical signals output by the cells in response to the stimulating step, contacting the cells with an agent, re-stimulating the cells with the same energy source and under the same conditions as the first stimulating step and for a time sufficient to depolarize the cells, measuring the QT interval of the electrical signals output by the cells in response to the second stimulating step, and comparing the results of the measuring taken after the first and second stimulating steps to determine whether the agent affects repolarization of cells. The present invention also provides a method for determining the effects of an agent on conduction of cells in vitro.
摘要:
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.
摘要:
A method of increasing the velocity of AV conduction in a mammal that may be in heart block or at risk of heart block by causing, in an AV node and/or His bundle having less than normal conduction speed, the expression of a sodium channel or gap junction protein, such as the SkM-1 channel, Cx43 or Cx32, so as to increase the velocity of conduction by the AV node.