51 results about "Heart cells" patented technology

The invention discloses a donor heart preservation method based on a crystal cardioplegic solution (CC solution) and a UW solution and application of the donor heart preservation method, and belongs to the field of biomedical engineering. The method comprises the following steps: (a) preparing CC liquid; (b) perfusing CC liquid through the aorta at the pressure of 150mmHg for 3-5 minutes to cause cardiac arrest; (c) taking out the heart, and performing secondary perfusion with 2000ml of 4 DEG C UW solution for 8-12 minutes; and (d) immersing the heart into a UW solution for cold preservation, wherein the cold ischemia time is less than or equal to 8 hours. In combination with a CC liquid perfusion step, the protection effect of the cold preservation liquid is remarkably improved by reducing the metabolic rate of cardiac cells; through double perfusion of CC liquid and UW liquid, optimization of metabolic balance and effective inhibition of inflammatory response are realized in the cold storage process of the heart; the invention has the functions of prolonging cold ischemia time and keeping heart cells, and provides a new technical means for long-time cold preservation.

The invention provides universally acceptable “off-the-shelf” hypoimmunogenic pluripotent cells and differentiated cardiac, endothelial, neuronal, islet, or retinal pigment cells thereof. Such hypoimmune cells are used to treat patients in need thereof. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis.

The present disclosure provides recombinant adeno-associated virus (rAAV) virions with an engineered capsid protein identified using a high-throughput sequencing screen or rational design. In particular, the disclosure provides AAV5 virions and capsid proteins with increased transduction efficiency in cardiac cells, increased cell-type selectivity, and / or other desirable properties.

A heart organoid of at least 60% cardiac cells irrespective of optional additional cells of a vascular system of the organoid, or including at least 50% cardiac cells; wherein the cardiac cells surround an inner cavity, wherein the cardiac cells are selected from the group of cardiomyocytes, endocardial cells and epicardial cells, and wherein the heart organoid includes cardiomyocytes or endocardial cells that directly face the inner cavity, a method for the generation of such a tissue model and uses thereof.

This disclosure relates generally to methods of screening and preparing cardiac cell therapies for potency (e.g., cardiac cell function).

Aspects of the disclosure relate to compositions and methods for delivering a transgene (e.g., a transgene encoding one or more gene products) to a target cell. The disclosure is based, in part, on adeno-associated virus (AAV) capsid protein variants characterized by tropisms for certain cell types (e.g., neurons, lung cells muscle cells, bone cells, heart cells, etc.). In some embodiments, recombinant AAVs (rAAVs) comprising the capsid protein variants described herein exhibit enhanced lung tropism when compared to rAAVs having certain wild-type AAV capsid proteins (e.g., AAV5). Methods of delivering an rAAV comprising the AAV capsid protein variants are also described by the disclosure.

The present disclosure describes ultrasound-based methods for facilitating the selective transduction of cardiac cells with therapeutic AAV vectors in vivo.

In certain embodiments, provided herein are compositions, kits, methods and uses that are useful for preventing or treating a subject suffering from one or more diseases, conditions or disorders associated with chemotherapy such as anthracycline treatment. In some embodiments, provided is a method of treating or preventing a disease, condition or disorder resulting from or exacerbated by chemotherapy treatment in a subject, comprising the step of: administering an effective amount of GDF15 to the subject prior to the chemotherapy. Other example embodiments are described herein. In certain embodiments, the provided novel compositions, kits, methods and uses are highly effective in reducing cardiac cytotoxicity, cheaper, and safer for use.

A computational system and method for digital modeling of biochemical reactions within cardiac cells are disclosed. The system comprises processors and a computer-readable storage device with instructions to maintain biological data related to cardiac cell reactions and receive user selections via a user interface to configure a simulation. The user can select a cardiac cell class, and functions to load cellular components, generate enzyme activity, load specific enzymes, and perform enzymatic reactions. The system performs in silico experiments, predicts new biological data, and compiles this into configuration data. An enzyme activity model is generated and simulated under various conditions, including user-defined enzymatic dysregulation, to replicate and study cardiac physiology and pathology. The results, such as changes in energy metabolism parameters like glucose consumption and ATP usage, are outputted. The system provides a detailed and interactive platform for research and education in cardiac electrophysiology and disease.

The invention discloses a preparation method and application of mesoderm-sourced heart mesenchymal stem cells, mesoderm-sourced CMSC is induced by hPSC, the differentiation path of the mesoderm-sourced CMSC is strictly limited through a specific induction culture solution, and the mesoderm-sourced CMSC is obtained after the mesoderm-sourced CMSC is subjected to the stages of mesoderm progenitor cells, cardiac progenitor cells and epicardial progenitor cells in sequence, and the mesoderm-sourced CMSC is clear in source and low in heterogeneity. The cardiac micro-tissue formed by assembling the cardiac muscle cells, the endothelial cells and the CMSC from the hPSC shows remarkable advantages in the aspects of cardiac micro-tissue polymerization capability and cardiac muscle cell maturation promotion, and related functions and repeatability of the model are improved; the requirements of a large-scale heart micro-tissue detection platform can be met; a new seed cell source is provided for cell therapy of cardiovascular diseases; a novel and high-quality cell source is provided for heart disease modeling and clinical transformation, especially for constructing heart micro-tissues, supporting heart cell transplantation, cell therapy of cardiovascular diseases and the like.

The utility model discloses a micro-fluidic chip culture box for nerve and heart co-culture, and relates to the technical field of cell co-culture. Comprising a box body and a box cover, a nutrient solution supply system, a liquid medicine supply system, a micro-fluidic chip and a waste liquid recovery system are arranged in the box body, a heart cell culture area and a nerve cell culture area are arranged on the micro-fluidic chip, and the heart cell culture area is connected with the nerve cell culture area through a controllable micro-channel; the nutrient solution supply system is used for providing nutrient solution for the heart cell culture area and the nerve cell culture area, the liquid medicine supply system is used for providing liquid medicine for the heart cell culture area and the nerve cell culture area, and the waste liquid recovery system is used for collecting waste liquid of the heart cell culture area and the nerve cell culture area. According to the utility model, the interaction between the heart and nerve cells in the body can be more accurately simulated, and the research efficiency and quality of heart disease models and nerve disease models are improved; the method can also be used for high-throughput drug screening, and accelerates the development process of new drugs.

The disclosure generally relates to methods, cells, and compositions for preparing cardiac extracellular matrix. In particular, provided herein are methods for preparing a cardiac extracellular matrix using SUSD2 High fibroblasts and SUSD2 High myofibroblasts.

The present technology provides compositions and methods for gene therapy and / or cell therapy for treatment of heart diseases. In particular, the present technology provides cardiac-specific promoters and vectors for expressing transgenes (e.g., large transgenes) in cardiac cells, for example, with the AAV system. The present technology also provides expression cassettes, recombinant AAV (rAAV) viral genomes, rAAV viruses or virions, pharmaceutical compositions, and methods of use in treatment or prevention of diseases (e.g., heart disease, such as cardiomyopathy).

Methods and systems for measuring viability and function of islet cells or stem cell-derived beta cells in an implantable device featuring setting the temperature of the cells in the implantable device to a low temperature to reduce metabolic levels of the cells and reduce oxygen requirements of the cells, and measuring oxygen consumption rates. An oxygen sensor at the inlet of the implantable device and an oxygen sensor at the outlet of the implantable device are used to calculate oxygen consumption rates of the cells, which in turn are indicative of viability. The reduction in temperature can also be used for loading cells into the implantable devices to help reduce ischemic and / or physical injury. The present invention may be used with other cell types, e.g. hepatocytes, heart cells, muscle cells, etc.

The invention provides application of a TP receptor inhibitor in preparation of a medicine for treating cardiac fibrosis, and relates to the technical field of biomedicine. According to the application, the key effect of the TP receptor in heart Gli1 + cells is defined, the TP receptor is determined as an anti-fibrosis specific drug target, and the limitation of insufficient targeting of the existing therapy is broken through. By inhibiting a TP receptor, an AMPK signal channel can be effectively activated, and then ubiquitination degradation of a fibrosis-promoting key factor Gli1 protein is promoted, so that generation and activation of myofibroblasts are inhibited from the source, and the fibrosis process is accurately intervened.

The application relates to recombinant adeno-associated virus particles comprising variant AAV capsid proteins (e.g., variant capsid proteins of serotype AAVrh74, AAVrh10, AAV8, or AAV1). Recombinant adeno-associated virus particles of the disclosure can be used to deliver exogenous nucleic acids (e.g., nucleic acids comprising genes encoding therapeutic RNAs or therapeutic proteins) to target cells, such as heart cells. In some aspects of the disclosure, the variant capsid proteins that comprise amino acid variations that alter the binding activity of recombinant adeno-associated virus particles to target cells, such as by increasing binding to heart cells and / or decreasing binding to liver cells. In some embodiments, the recombinant adeno-associated virus particles are utilized in a method of treating subject. In some embodiments, such methods are utilized in delivering exogenous nucleic acids to target cells more specifically and / or at lower doses compared to other recombinant adeno-associated particle delivery systems.

The present invention provides recombinant adeno-associated viral vectors which are enriched in the heart but have reduced enrichment in other organs, particularly the liver and CNS cells, for use in the treatment of acquired and genetic left and right heart diseases as well as other diseases associated directly or indirectly with cardiac dysfunction.

The present disclosure provides variant AAV capsid polypeptides that, when present in the capsid of an AAV vector, facilitate efficient transduction of cardiac cells, in particular human cardiac cells. Also provided are methods for preparing AAV vectors, in particular vectors that transduce cardiac cells, and in particular AAV vectors for gene therapy uses, in particular those targeting the heart or cardiac cells and tissue.

To provide cardiomyocytes and compositions, and methods for producing the same.SOLUTION: Disclosed herein are methods for generating mature cardiomyocytes, and compositions including the mature cardiomyocytes. Also disclosed herein are methods for enhancing maturation of quiescent cardiomyocytes, and compositions including the mature quiescent cardiomyocytes. There is a need for methods or protocols for the generation of mature cardiomyocytes for use in cell therapy and cell screening, among other uses. By leading cardiomyocytes to a quiescent state, maturation of the cardiomyocytes may be enhanced. Disclosed herein are methods of producing a mature cardiomyocyte from an immature cardiomyocyte. The methods comprise contacting the immature cardiomyocyte with an mTOR inhibitor.SELECTED DRAWING: None

The invention discloses a plant composition capable of efficiently activating anti-hypoxia activity of cardiac cells and a preparation method thereof.The preparation method comprises the steps that cardamine violifolia and rhodiola rosea are smashed and then mixed and pulped, water is added, pectinase, cellulase and hemicellulase are added for ultrasonic enzymolysis after high-pressure homogenization, centrifugal separation is performed, and a mixture is obtained; and after filtering, freezing and drying the supernate to obtain a mixed extract of cardamine violifolia and rhodiola rosea. According to the method, plant cell walls are crushed firstly through ultrahigh pressure extraction, functional components in cells are released, the functional components are dissolved in an extracting solution to the maximum extent under the action of enzymolysis and ultrasound, meanwhile, it can be guaranteed that chemical bonds of the functional components are not damaged, and the structural integrity and biological activity of the functional components are reserved to the maximum extent. The cardamine violifolia and the rhodiola rosea in the mixed extract have a synergistic effect, so that the taste of the product can be improved and the purpose of reducing the cost can be achieved under the condition that the use amount and the use period of the rhodiola rosea can be reduced.

The present invention relates to a pharmaceutical composition for prevention and treatment of heart failure. Specifically, the present invention relates to a gene construct comprising a polynucleotide coding for SERCA2a protein or a fragment thereof and a polynucleotide coding for CCN5 protein or a fragment thereof, and a pharmaceutical composition comprising the same construct as an effective ingredient for preventing or treating heart failure. A pharmaceutical composition for prevention and treatment of heart failure according to the present invention is used in a method for co-expression of SERCA2a protein and CCN5 protein. Designed to exert a synergistic therapeutic effect through SERCA2a protein's function of preventing the loss of cardiomyocytes and increasing the activity of cardiomyocytes and CCN5 protein's function of suppressing the fibrosis of heart cells and tissues, the pharmaceutical composition can be useful for preventing or treating heart failure, which is a complex disorder induced by various etiological factors.

The present invention discloses an application of an artificially designed novel NRG-1 in disease treatment. The present invention provides a nucleic acid molecule, an NRG1 protein variant, a vector, a vaccine, a cell, a pharmaceutical composition and a protein composition. The present invention also provides the following methods: a method for producing a protein, a method for producing a primary RNA polynucleotide. The present invention also provides the following applications: application in preparing a product for preventing, alleviating or treating cardiovascular diseases, application in preparing a product for preventing, alleviating or treating neurological diseases, application in preparing a product for maintaining the normal function of cardiac cells or tissues, and application in preparing a vaccine.

The application discloses application of SFRP3 in prevention and treatment of dilated cardiomyopathy, and belongs to the technical field of biological medicine. The application down-regulates SFRP3 expression in myocardial cells by means of gene interference, RNA interference technology, antibody or small molecule inhibitor, etc. to treat dilated cardiomyopathy, realizes the purposes of improving heart function, reducing cardiac dilatation, improving myocardial fibrosis and effectively promoting myocardial repair, and provides a more effective and low-side-effect treatment method for treatment of dilated cardiomyopathy. The treatment idea provided by the application can not only relieve symptoms of dilated cardiomyopathy, but also regulate physiological processes of heart cells at a molecular level, and provides a new idea for clinical treatment of dilated cardiomyopathy.

The present disclosure describes ultrasound-based methods for facilitating the selective transduction of cardiac cells with therapeutic AAV vectors in vivo.

The invention discloses a cardiac function preparation as well as a preparation method and application thereof, and belongs to the technical field of preparation of cardiac muscle repair stem cell preparations. Performing mixed culture on endothelial progenitor cells and a heart extracellular matrix to obtain composite cell spheres; carrying out mixed culture on the myocardial-like cell sheet and the composite cell spheres, and after the composite cell spheres are uniformly distributed on the cell sheet and are in a fusion trend, cutting the composite cell spheres into pieces to obtain cell sheet-cell sphere composite particles; and uniformly mixing the composite particles with a poloxamer P407 solution to obtain the heart function preparation. Wherein the endothelial progenitor cells are combined with the cardiac extracellular matrix for use, so that angiogenesis in cardiac tissues can be effectively promoted, cell spheres and myocardial-like cell patches are compounded and cut into pieces, and the pieces can be better adhered to myocardial infarction positions for targeted repair. Experiments prove that the cardiac function preparation can effectively promote angiogenesis of cardiac tissue and myocardial infarction tissue repair, and the problem that the repair function is limited due to the fact that the number of survival cells is insufficient after cell transplantation in a stem cell therapy is solved.

Methods and systems for cardiomyocyte maturation are generally described. In some embodiments, immature cardiomyocytes may be incubated with a three-dimensional matrix in an incubation medium and permitted to mature over a period of several weeks. In some embodiments, the three-dimensional matrix may include at least one population of microcarriers. The systems for cardiomyocyte maturation are evaluated for their scalability to meet large-scale global demand for cardiac cell therapies.

The present technology provides compositions and methods for gene therapy and / or cell therapy for treatment of heart diseases, e.g., atrial fibrillation. In particular, the present technology provides transgenes, expression cassettes, vectors, recombinant AAV (rAAV) viral genomes, rAAV viruses or virions, and pharmaceutical compositions for overexpressing synaptopodin 2 like (SYNPO2L), isoform A (SYNPO2LA) in a cardiac cell in a subject, as well as methods of using the same in the prevention or treatment atrial fibrillation.

This disclosure provides methods to modulate cardiac regeneration in a mammalian cardiac cell or progenitor, comprising contacting the mammalian cardiac cell with a DOT1L gene modulator.

The present invention provides a heart tissue model of at least 60% cardiac cells, wherein the cardiac cells surround an inner cavity, wherein the cardiac cells are selected from cardiomyocytes, endocardial cells and epicardial cells; method for the generation of such a tissue model and uses thereof.

This disclosure relates generally to methods of screening and preparing high purity cardiac cell therapies and related cell preparations.