357 results about "Cells heart" patented technology

A method for extinguishing a cardiac arrhythmia utilizes destructive interference of the passing of the reentry wave tip of an anatomical reentry through a depolarized region created by a relatively low voltage electric field in such a way as to effectively unpin the anatomical reentry. Preferably, the relatively low voltage electric field is defined by at least one unpinning shock(s) that are lower than an expected lower limit of vulnerability as established, for example, by a defibrillation threshold test. By understanding the physics of the electric field distribution between cardiac cells, the method permits the delivery of an electric field sufficient to unpin the core of the anatomical reentry, whether the precise or estimated location of the reentry is known or unknown and without the risk of inducting ventricular fibrillation. A number of embodiments for performing the method are disclosed.

A method for extinguishing a cardiac arrhythmia utilizes destructive interference of the passing of the reentry wave tip of an anatomical reentry through a depolarized region created by a relatively low voltage electric field in such a way as to effectively unpin the anatomical reentry. Preferably, the relatively low voltage electric field is defined by at least one unpinning shock(s) that are lower than an expected lower limit of vulnerability as established, for example, by a defibrillation threshold test. By understanding the physics of the electric field distribution between cardiac cells, the method permits the delivery of an electric field sufficient to unpin the core of the anatomical reentry, whether the precise or estimated location of the reentry is known or unknown and without the risk of inducting ventricular fibrillation. A number of embodiments for performing the method are disclosed.

Disclosed are methods and systems for modulating electrical behavior of cardiac cells. Preferred methods include administering a polynucleotide or cell-based composition that can modulate cardiac contraction to desired levels, i.e., the administered composition functions as a biological pacemaker.

A method of generating cells predominantly displaying at least one characteristic associated with a cardiac phenotype is disclosed. The method comprises (a) partially dispersing a confluent cultured population of human stem cells, thereby generating a cell population including cell aggregates; (b) subjecting said cell aggregates to culturing conditions suitable for generating embryoid bodies; (c) subjecting said embryoid bodies to culturing conditions suitable for inducing cardiac lineage differentiation in at least a portion of the cells of said embryoid bodies, said culturing conditions suitable for inducing cardiac lineage differentiation including adherence of said embryoid bodies to a surface, and culture, medium supplemented with serum, thereby generating cells predominantly displaying at least one characteristic associated with a cardiac phenotype.

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.

The present invention generally relates to the field of cell growth and tissue engineering, in particular, tissue engineered compositions comprising a nanotextured substrate which is structurally configured for growth of cells in an anatomically correct adult phenotype in vitro. In particular, described herein are nanotextured substrates which are structurally configured for the anisotropic organization, maturation, and growth of in vitro-differentiated muscle cells, such as cardiomyocytes, and methods for the production and use thereof in varying sizes, nanotextures and substrate rigidities. In vitro-differentiated cardiomyocytes grown on the nanotextured substrates described herein are better-differentiated and more closely mimic adult cardiac tissue than the same cells grown on a non-textured substrate of the same composition. The nanotextured substrate / cell constructs provide a platform for screening to predict the effect of test agents or drugs on, for example, human cardiac tissue, including patient-derived tissue, or for the identification of agents that effect various cardiac functional parameters.

Methods for generating high-yield, high-purity cardiomyocyte progenitors or cardiomyocytes from pluripotent cells are described. Wnt / β-catenin signaling is first activated in pluripotent cells, e.g., by inhibition of Gsk-3 to obtain a first population of cells. Wnt / β-catenin signaling is then inhibited in the first cell population to induce cardiogenesis under fully defined, growth factor free culture conditions.

The invention belongs to the field of researching and application of biomedicine and particularly relates to human pluripotent stem cell-hereditary cardiomyopathy cardiac muscle cells and a preparation method thereof. The invention provides a human hereditary cardiomyopathy-pluripotent stem cell, which is constructed by means of TALEN or CRISPR / CAS9 genome editing technology. The human hereditary cardiomyopathy cardiac muscle cell can be combined with any scaffold materials to culture various in-vitro human hereditary cardiomyopathy cardiac muscle tissues. The human hereditary cardiomyopathy cardiac muscle cells in the invention have disease phenotypes and electrophysiology change being similar as the cardiac muscle cells of human hereditary cardiomyopathy patients. The human hereditary cardiomyopathy cardiac muscle cells are wide in sources and can be cultured in-vitro for a long time. The invention provides excellent tools and platforms for researching an effective new therapy means and researching an effective corresponding treatment medicine.

The present invention provides a method for repairing damaged myocardium. The method comprises using a combination of cellular cardiomyoplasty and electrostimulation for myogenic predifferentiation of stem cells and to synchronize the contractions of the transplanted cells with the cardiac cells. The method comprises the steps of obtaining stem or myogenic cells from a donor, culturing and electrostimulating the isolated cells in vitro, and implanting the cells into the damaged myocardium.

The present invention generally relates to methods and compositions to generate a secondary iPS (2iPS) cell to produce somatic cells of a rare differentiation cell type fate. In some embodiments, the method relates to an increase in efficiency of differentiation and production of high yields of somatic cells of a rare differentiation cell type fate produced from secondary iPS (2iPS) cells as compared to their differentiation from other pluripotent stem cell sources such as ES cells or primary iPS cells. In some embodiments, the present invention relates to compositions, methods and systems for reprogramming a first somatic cell into a primary iPS cell, where the primary iPS cell is then differentiated along a selected linage to produce a second somatic cell, which is then reprogrammed to a secondary iPS cell (2iPS) cell. The 2iPS cell has a high efficiency of differentiating into a cell of the same cell type as the second somatic cell, e.g., a somatic cells of a rare differentiation cell type fate such as but not limited to a ventricular cardiomyocyte, a pancreatic β-cell or a hepatic cell. In some embodiments, the first somatic cell is a fibroblast, or a cardiac cell, but is not limited to cardiac fibroblast cells. In some embodiments, the present invention relates to compositions, methods and systems to produce ventricular cardiomyocytes from secondary induced pluripotent stem cells (iPSC), where the iPSC are themselves generated from ventricular cardiomyocytes. The secondary iPS (2iPS) cell generated from ventricular cardiomyocytes have a higher cardiomyogenic potential and high cardiomyogenic yield as compared to primary iPSC, and are useful in drug discovery, disease modeling and cell-based therapy.

The present invention provides a method for repairing damaged myocardium. The method comprises using a combination of cellular cardiomyoplasty and electrostimulation for myogenic predifferentiation of stem cells and to synchronize the contractions of the transplanted cells with the cardiac cells. The method comprises the steps of obtaining stem or myogenic cells from a donor, culturing and electrostimulating the isolated cells in vitro, and implanting the cells into the damaged myocardium.

The invention provides a method for directionally differentiating a multipotential stem cell in vitro into a myocardial cell and provides a culture medium for establishing myocardial cell differentiation by means of induction in vitro under a three-dimensional suspension condition. The culture medium comprises a differential medium for induced differentiation of a multipotential stem cell into a precursor cell of mesoblast, a differential medium for differentiating the precursor cell of mesoblast into the myocardial cell and a long-term maintaining culture medium of the myocardial cell. The method provided by the invention is simple and reliable, low in cost, stable and efficient and high in safety. By adopting a suspension culture system, high-quality myocardial cells can be industrially produced without any subsequent screening and purifying steps, can be directly used for application demands of scientific research of heart development, cell therapy of heart diseases, transplanting due to cardiac trauma and drug screening, and has inestimable scientific, social and economical benefits.

Devices, systems and methods for monitoring excitable cells, such as cardiomyocytes, on microelectrode arrays that couple the electro-stimulation of excitable cells to induce or regulate cardiomyocyte beating and the simultaneous measurement of impedance and extracellular recording to assess changes in cardiomyocyte beating, viability, morphology or electrophysical properties in response to a plurality of treatments.

The invention discloses an inducing culture medium for inducing fibroblast to trans-differentiate into cardiac muscle cells, a method and an application of the inducing culture medium. The inducing culture medium comprises a basic culture medium and an inducing small molecular assembly which is 6TCFOW or SCFOV, wherein 6 is E61541, T is tranylcypromine, C is CHIR99021, F is forskolin, O is Dorsomorphin, W is IWR-I, S is SB431542, and V is valproic acid. The inducing culture medium can trans-differentiate the fibroblast into the cardiac muscle cells which have normal cardiac muscle cell specific molecular tags and a normal cardiac muscle function, so that a new way is provided for solving the cell source problem of the regenerative medicine.

Disclosed is a method for culturing myocardium-resident cardiac progenitor cells, comprising: embedding myocardial fragments into hydrogel; culturing the myocardial fragment into hydrogel; degrading only the hydrogel to recover cardiac progenitor cells grown out of the myocardial fragment to the hydrogel; and amplifying the cardiac progenitor cells in vitro. Also, the cardiac progenitor cells, a method for differentiating the same, and the use thereof as cell therapeutic agent for heart diseases are provided. In addition to possessing the potential to differentiate into cardiomyocytes, osteoblasts, adipocytes, chondrocytes, vascular endothelial cells, smooth muscle cells, neural cells, and skeletal muscle cells, the myocardium-resident cardiac progenitor cells can spontaneously differentiate into cardiomyocytes even in the absence of a special differentiation inducing agent. Thus, the cardiac progenitor cells can be used to produce bio-active medicines such as cell therapeutics and tissue engineering therapeutics with high industrial applicability.

A system forms a cardiac conduction block at a location in a heart of a patient without substantially ablating cardiac tissue. The system includes a delivery system coupled to a source of material that is substantially non-ablative with respect to cardiac tissue. The delivery system delivers the material to the location, and the material at the location forms a conduction block without ablating the cardiac cells there. The material may include living cells, such as for example skeletal myocytes, and / or may include a non-living matter such as biopolymers such as a fibrin glue agent, or collagen agents. An expandable member with needle assembly is used to deliver the material so as to form a non-ablative circumferential conduction block at a location where a pulmonary vein extends from an atrium.

A system forms a cardiac conduction block at a location in a heart of a patient, generally without substantially ablating cardiac tissue. The system includes a delivery system coupled to a source of material that is substantially non-ablative with respect to cardiac tissue but that substantially interrupts and thus blocks cardiac conduction. The delivery system delivers the material to the location, and the material at the location forms a conduction block without substantially ablating the cardiac cells there. The material includes a synthetic polymer, a polysaccharide (e.g. block polysaccharide, alginate, etc.), or a protein, or an analog, derivative, precursor, or agent thereof, or a combination or blend thereof. The material may include living cells. The delivery assembly may include a needle for injecting the material. An expandable member is provided with a needle assembly to deliver the material and form a non-ablative circumferential conduction block where a pulmonary vein extends from an atrium.

The present invention provides novel nucleic acid and protein sequences for methods and compositions for treating, screening, and diagnosing cardiovascular disease and methods for using these genes and gene products for prevention of cardiac cell death and prevention of cardiac tissue damage resulting from ischemic events in cardiac tissue, as well as other tissue that is subject to damage resulting from an ischemic event. The genes, gene products and agents of the invention are also useful for treating other related clinical or coronary events such as angina, myocardial infarct (MI), and stroke, for monitoring the effectiveness of their treatment, and for drug development. The genes, gene products and agents of the present invention are also provided as pharmaceutical compositions for treatment of cardiovascular disease, ischemic heart disease, myocardial infarct and related conditions. Kits are also provided for the diagnosis, treatment and prognosis of cardiac diseases and related conditions.

The invention provides methods for establishing electrical coupling between cardionyocytes and recombinant cells which have been genetically engineered to express a gap junction protein, eg., Connexin protein such as Connexin 43 (CX43) protein, n invention is based on the discovery that genetic modification of skeletal muscle cells to express a recombinant connexin, enables the genetically modified cells to establish electrocommunication with cardiac cells via gap junctions. The recombinant connexin-expressing cells can be used for repair of cardiac issue and for treatment of cardiac disease by transplantation into cardiac tissue.

An object of the present invention is to establish a cell transplantation method which can markedly improve the survival of grafted pluripotent stem cells and the efficiency of cardiomyocyte regeneration in cell therapy using pluripotent stem cells derived from heart tissue and can treat heart disease further effectively. Specifically, according to the present invention, enhancement in the survival of grafted pluripotent stem cells and significant improvement in the efficiency of cardiomyocyte regeneration are achieved by using, in combination, pluripotent stem cells derived from heart tissue and a hydrogel containing a basic fibroblast growth factor (bFGF) in cell therapy for heart disease.

A method for treating cardiac fibrosis resulting from injury of a mammalian heart is described comprising the step of contacting a therapeutically effective amount of relaxin and / or an LGR7 activating agent with cardiac cells following the injury in an amount sufficient to reduce the fibrosis. Also described are methods for protecting the heart following an ischemic event, inhibiting the proliferation of activated fibroblasts and antagonising collagen secretion or deposition in a mammalian heart.

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mesp1, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mesp1, Mesp2, Gata4, Gata6, Baf60c, SRF, Isl1, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

The present invention relates to a composition for promoting differentiation of pluripotent stem cells into cardiac muscle cells, and a method for inducing differentiation of pluripotent stem cells into cardiac muscle cells and a method for preparing cardiac muscle cells.

The present invention provides delivery systems for and methods of delivering ion channel protein genetic material to cardiac cells in areas adjacent to where an electrode is to be positioned in a patient's heart to improve or correct the signal to noise ratio of cardiac signals, such as the P-wave. More specifically, there is provided a system and method for delivering sodium ion channel proteins or nucleic acid molecules encoding sodium ion channel proteins to a site in the heart adjacent to an electrode to increase the expression of the same, thereby enhancing the cardiac signal amplitude and enabling improved sensing of cardiac signals by an implanted pacemaker.

Methods for generating high-yield, high-purity cardiomyocyte progenitors or cardiomyocytes from pluripotent cells are described. Wnt / β-catenin signaling is first activated in pluripotent cells, by, for example, inhibiting Gsk-3 to obtain a first population of cells. Wnt / β-catenin signaling is then inhibited in the first cell population to induce cardiogenesis. One or more of these steps is performed under defined, albumin-free culture conditions.

The invention relates to the method for measuring single alive myocardial cell action potential and the pulsing force by an atomic force microscope. An atomic force microscope conductive probe is used as a nanometer electrode to measure the operation potential of the single pulsing mouse myocardial cell; the probe is accurately positioned on a cell to be detected through the atomic force microscope which is independently developed and according to a force feedback system; the probe and the cell surface have two contact forms which are a constant force contact mode and a non-constant force contact mode; and the variable measurement of the action potential and the pulsing force is performed on the myocardial cell through the two modes. The measurement on the myocardial cell action potential can accurately determine the position of the myocardial cell, and realizes the fixed point measurement. The invention can obtain the high signal-noise ratio action potential signal waveform and can simultaneously measure the action potential of the myocardial cell, ie, the changing signal of the pulsing force.

The invention relates to a preparation method of a mesenchymal stem cell exosome. The preparation method comprises the following steps: culturing mesenchymal stem cells for several hours by using a serum-free conditioned culture medium, centrifuging and removing the cells, collecting a liquid supernatant crude product, then re-centrifuging, filtering, and removing the residual cells as well as cell debris to prepare liquid supernatant containing an exosome; preparing the exosome by stepwise centrifugation of polyethylene glycol adopted by the liquid supernatant containing the exosomes. Exosome-expressed specific proteins CD63 prepared by the preparation method provided by the invention can effectively improve the mitochondria damage of the myocardial cells, prevent the cell apoptosis and improve the functions of the myocardial cells and are used for preparing a drug for treating myocardial ischemia reperfusion injury.