188 results about "Cell subpopulations" patented technology

The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism a toxin which causes killing of the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon / intron boundaries of pre-mRNA molecules using an exon tagging method. The PTMs of the invention can also be designed to result in the production of chimeric RNA encoding for peptide affinity purification tags which can be used to purify and identify proteins expressed in a specific cell type.

The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time: quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

The present invention provides an approach for the simultaneous determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of potentiators of cellular activation allows for characterization of such pathways and cell populations.

Markers useful for the identification, characterization and, optionally, the enrichment or isolation of tumorigenic cells or cell subpopulations are disclosed.

Markers useful for the identification, characterization and, optionally, the enrichment or isolation of tumorigenic cells or cell subpopulations are disclosed.

Disclosed are cells, methods of modulating cells, and therapeutic uses of the cells for the immune modulation of mammals in need thereof. Immune modulation including alteration of cytokine profile, cytotoxic activity, antibody production and inflammatory states is achieved through the administration of various cell types that have been unmanipulated or manipulated in order to endow specific biological activity. Cellular subsets and administration of the subsets in combination with various agents are also provided. One embodiment teaches the previously unknown finding that adipose tissue derived mononuclear cells contain T cells with immune regulatory properties that alone or synergistically with various stem cells induce immune modulation upon administration. Another embodiment is the finding that stimulation of stem cell activation results in stem cell secondary activation of immune modulatory cells, one type which is T regulatory cells (Tregs). One specific embodiment involves extraction of a heterogenous stem cell pool, which contains T regulatory cells, treatment in culture of the population with agents known to stimulate stem cell activation, then subsequent extraction and administration of the purified Tregs. Other embodiments include expansion of Tregs in the presence of antigen in order to generate anti-specific Tregs.

Markers useful for the identification, characterization and, optionally, the enrichment or isolation of tumorigenic cells or cell subpopulations are disclosed.

This invention comprises a novel approach to the assessment of antigen-specific T cells that quantitates and characterizes these cells with unprecedented clarity, and importantly, because it is performed in whole blood, is amenable to routine use in the clinical immunology laboratory. The methodology offers an improved flow cytometric intracellular cytokine assay in whole blood that can simultaneously measure multiple T cell subsets expressing multiple cytokines from a single whole blood culture. Evaluation of whole blood antigen specific cytokine responses has the important advantage of assessing T cell activation in the presence of ALL types of MHC autologous antigen presenting cells present in the native sample. It also has the advantage of enabling a culture system (whole blood) which can reflect effects of systemic environments (i.e. drug augmentation or suppression) on T cell responses to specific stimuli including antigen, by either culturing in the presence of such drug or analyzing the blood of a human or animal receiving such drug.

Markers useful for the identification, characterization and, optionally, the enrichment or isolation of tumorigenic cells or cell subpopulations are disclosed.

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders. Additionally, methods are provided for the diagnostic evaluation and prognosis of TH cell subpopulation-related disorders, for the identification of subjects exhibiting a predisposition to such conditions, for monitoring patients undergoing clinical evaluation for the treatment of such disorders, and for monitoring the efficacy of compounds used in clinical trials.

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders. Additionally, methods are provided for the diagnostic evaluation and prognosis of TH cell subpopulation-related disorders, for the identification of subjects exhibiting a predisposition to such conditions, for monitoring patients undergoing clinical evaluation for the treatment of such disorders, and for monitoring the efficacy of compounds used in clinical trials.

The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell population.

The invention provides the appraisal and selective method for the antineoplastic drug based on the cell micrograph information, which uses a sort of selection and appraisal hardware system to appraisal and select the antineoplastic drug by different fluorescence dye marking and measuring the multicellular parameter change in cell. The hardware system is made up of the high precision electric hydrous platform, the fluorescence vision system, the image collecting and processing system and working station. The diacetoxyl fluoresceine dyeing measures the active cell number; the double dyeing method of Hoechst33342 and iodized pyridine appraise the drug inducing the cell die; the three dyeing method of FDA, Hoechst33342 and PI analyzes the die mode induced by drug. The invention can measure at least two kinds of single cell or cell subgroup which expresses different drone cell organ. The method is in reason and can be used in study of drug action mechanism and selecting the high hedonic drug and toxicity analyzing, which can be used in selecting drug and appraising the drug toxicity.

The invention discloses a flow cytometry device for a no-flow type cytometry box and a flow cytometry method for the no-flow type cytometry box. The device adopts a unique kurt microporous direct coaxial illumination method, so that the necessary expensive flow cytometry box and the complex liquid focusing in the existing mainstream flow cytometry can be thoroughly abandoned, the structure can be simplified, the cost can be reduced, the interaction time between the cell and the excited laser can be prolonged by tens of times, the sensitivity of the apparatus can be improved by orders of magnitude, the backward scattering light which is most sensitive to the structures and the components in the cells can be firstly and successfully applied to the actual commercial flow cytometry due to the unique structure, and the identifying capability of the apparatus to the different cell subsets can be improved. A multi-wavelength excited laser combiner and a multi-wavelength fluorescent detection system of a new device all adopt a single dispersing element, so that the loss of the apparatus can be reduced to the lowest level, and the overlap of the wavelengths can be reduced. Compared with the flow type cytometry which is universally used in the world, the flow cytometry device is obvious in cost performance and market advantage.

A method of determining cell cycle phase data for cells comprising at least one luminescent reporter capable of emitting radiation, the at least one luminescent reporter comprising a first luminescent reporter which is capable of being indicative of at least one cell cycle phase, said method comprising: storing classification information for classifying individual cells into different cell cycle phases using an automated classification process; receiving image data created by detecting radiation emitted by said at least one luminescent reporter; analyzing said image data to identify object areas in the image data which correspond to individual cells; analyzing said image data, on the basis of said identified object areas, to determine, for a selected cell, one or more measurements including a measurement of a parameter relating to at least a cytoplasmic component of the cell; and applying said classification information to said measurements to classify the selected cell into a selected one of a plurality of sub-populations of cells, each sub-population having cells in a different cell cycle phase.

The present invention relates to a distinct B cell subset, B10 cells, that regulate T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-10). The invention also relates to the use of B10 cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of B10 cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of B10 cells, or inhibition of their IL-10 production can be used to upregulate immunodeficient conditions, ameliorate infectious diseases and / or to treat tumors / cancer. Diagnostic applications are also encompassed.

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders. Additionally, methods are provided for the diagnostic evaluation and prognosis of TH cell subpopulation-related disorders, for the identification of subjects exhibiting a predisposition to such conditions, for monitoring patients undergoing clinical evaluation for the treatment of such disorders, and for monitoring the efficacy of compounds used in clinical trials.

In accordance with one aspect of the present invention, methods have been developed for identifying compositions which support the culture of defined cell populations. In accordance with another aspect of the present invention, methods have been developed for identifying compositions which promote differentiation of defined cell populations. In accordance with yet another aspect of the present invention, methods have been developed for identifying compositions which induce apoptosis of defined cell populations. In accordance with still another aspect of the present invention, methods have been developed for identifying compositions which promote cell senescence of defined cell populations. In accordance with still another aspect of the present invention, methods have been developed for identifying media which modulate the retardation of cell growth of defined cell subpopulation(s). In accordance with further aspects of the present invention, there are provided novel compositions identified by invention methods. Also provided are various uses of the novel compositions identified by invention methods, and novel cell populations produced employing same. In accordance with still another aspect of the present invention, methods have been developed for identifying compositions which support the culture of aberrant cell populations. In accordance with yet another aspect of the present invention, methods have been developed for identifying compositions which promote differentiation of aberrant cell populations. In accordance with still another aspect of the present invention, methods have been developed for identifying compositions which induce apoptosis of aberrant cell populations.

Provided herein are methods that enable parallel evaluation of multiple functional nucleic acids in individual cells or subpopulations of cells, in the context of incubation with other types of single cells. The key insight is concurrent measurement of polynucleic acids derived from small populations of at least two different cell types, such that function in one cell type is linked to the clonal identity of another cell. These methods simultaneously process thousands, millions, or more single cells or small populations of cells. The method integrates molecular, algorithmic, and engineering approaches. This invention has broad and useful application in a number of biological and medical fields, including immunology and drug discovery.

The invention discloses T cell subsets in lung cancer and feature genes thereof. A single-cell transcriptome analysis technology is adopted, and by analyzing a single-cell gene expression profile of infiltrating T cells in the lung cancer tissue, the T cell subsets capable of reflecting body tumor immune states of patients with the lung cancer are separated and characterized, namely the exhaustedCD 8+ T cells or regulatory T cells capable of expressing genes including TNFRSF9, TNFRSF18 and LAYN are separated and characterized. Through research, relations between lung cancer prognosis and thenew feature genes which include TNFRSF9, TNFRSF18 and LAYN and are expressed by the cell subsets are further determined. Therefore, the T cell subsets in lung cancer and the feature genes thereof canbe used for diagnosis and monitoring of lung cancer prognosis and serve as new targets for lung cancer immunotherapy.

The invention provides for detecting target subpopulations of cells that have high proliferative and renewal properties in animals, including circulating tumor cells, cancer stem cells, hematopoietic stem cells and endothelial progenitor cells. The invention utilizes a defined substrate and media of known property to enrich target cell subpopulations which can be used for future genetic, proteomic and morphological analyses. The method can use image-capture and analysis software to characterize cells based on physical properties, such as size, morphology and kinetic properties.

The present invention relates generally to kits that provide reagent mixes and instructions for the use thereof, in performing high-throughput assay methods that determine the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells. The present invention further relates to kits that provide reagent mixes and instructions for high-throughput assays methods for screening compounds that may modulate the proliferative status of a target cell population. The kits of the present invention and methods therein described may be used for determining the proliferative status of any isolated cell line or type. The kits and methods of the present invention address the need for rapid assays that determine the proliferative status of isolated hematopoietic stem and progenitor cells and of subpopulations of differentiated cells thereof.

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders, and also for the treatment of mast cell-related processes and disorders, ischemic disorders and injuries, including ischemic renal disorders and injuries. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders. Additionally, methods are provided for the diagnostic evaluation and prognosis of TH cell subpopulation-related disorders, for the identification of subjects exhibiting a predisposition to such conditions, for monitoring patients undergoing clinical evaluation for the treatment of such disorders, and for monitoring the efficacy of compounds used in clinical trials. Methods are also provided for the treatment of symptoms associated with mast cell-related processes or disorders and ischemic disorders and injuries using the genes, gene products and antibodies of the invention.

The described invention provides a method for in vitro immunoactivation of mononuclear cells by contact with one or more populations of engineered leukocyte stimulator cells genetically engineered to express a core of 3 essential immunomodulator peptides, and optionally additional R immunomodulator peptides, and use of a cell product comprising the expanded and activated mononuclear cell population comprising one or more subpopulations of cytotoxic serial killer cells for passive immunization of a cancer patient not currently under the influence of an immunosuppressive regimen.

The invention provides a cell subset annotation method based on single cell transcriptome sequencing. The cell subset annotation method comprises the following steps: 1) 10x barcode UMI identification; 2) genome comparison; 3) gene expression profile comparison; 4) low-quality cell filtering and data homogenization; 5) cell population clustering; 6) marker gene extraction; 7) cell subset annotation. The invention belongs to the technical field of biological information analysis, and provides a cell subset annotation method based on single-cell transcriptome sequencing, which solves the problem of single-cell subset annotation, so that single-cell sequencing data can support cell annotation according to a gene expression profile and / or a cell Marker gene after conventional analysis. Therefore, organic combination of different annotation methods is realized, and the distribution condition and related information of cell types are obtained.

The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism a toxin which causes killing of the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon / intron boundaries of pre-mRNA molecules using an exon tagging method. The PTMs of the invention can also be designed to result in the production of chimeric RNA encoding for peptide affinity purification tags which can be used to purify and identify proteins expressed in a specific cell type.

The described invention provides pharmaceutical compositions for treating an infarct area injury and methods of treating or repairing the infarct area injury in a revascularized subject in the aftermath of an acute myocardial infarction resulting from a natural disease process by administering to the subject parenterally through a catheter a sterile pharmaceutical composition containing a therapeutically effective amount of a nonexpanded sterile isolated chemotactic hematopoietic stem cell product as a first therapeutic agent and optionally a therapeutically effective amount of at least one compatible second therapeutic agent. The infarct area-improving amount of the sterile isolated chemotactic hematopoietic stem cell product comprises an enriched population of isolated autologous CD34+ cells containing a subpopulation of potent cells expressing CXCR-4 and having CXCR-4-mediated chemotactic activity such that the enriched population of isolated autologous CD34+ hematopoietic stem cells provides at least 0.5×106 potent CD34+ cells expressing CXCR-4 and having CXCR-4 mediated chemotactic activity.

The present invention relates to pharmaceutical compositions comprising a chemotactic hematopoietic stem cell product comprising an enriched population of CD34+ cells containing a subpopulation of CD34+ / CXCR-4+ cells having CXCR-4-mediated chemotactic activity, methods of preparing these compositions and use of these compositions to treat or repair vascular injury, including infarcted myocardium.