328 results about "Bone marrow cell" patented technology

The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO   (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position −1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of −1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.

Methods of establishing hematopoietic chimerism useful to correct hematological diseases and promote acceptance of organ transplants include administering busulfan, costimulation blockade, and readily attainable numbers of T-cell depleted bone marrow cells.

The invention is directed toward a sterile cartilage defect implant material comprising milled lyophilized allograft cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers with allogenic chondrocytes or bone marrow cells in an amount exceeding the natural occurrence of same in hyaline cartilage and adding a cell growth additive.

Bone marrow stromal cells (BMSC) differentiate into neuron-like phenotypes in vitro and in vivo, engrafted into normal or denervated rat striatum. The BMSC did not remain localized to the site of the graft, but migrated throughout the brain and integrated into specific brain regions in various architectonic patterns. The most orderly integration of BMSC was in the laminar distribution of cerebellar Purkinje cells, where the BMSC-derived cells took on the Purkinje phenotype. The BMSC exhibited site-dependent differentiation and expressed several neuronal markers including neuron-specific nuclear protein, tyrosine hydroxylase and calbindin. BMSC can be used to target specific brain nuclei in strategies of neural repair and gene therapy.

An automatic method for analyzing nucleated bone marrow cells comprising partitioning one sample of bone marrow fluid with two samples, one sample being treated with a first lysing agent and a first staining solution and the other sample being treated with a second lysing agent and a second staining solution; and measuring each samples in a flow cytometer using a scattered light and fluoresence which enables to classify and count leukocytes, erythroid cells and lipid particles, as well as mature myeloid cells, lymphoid cells and immature myeloid cells, and to calculate the number of myeloid cells as well as the ratio of myeloid cells and erythroid cells.

Methods and apparatuses for the separation a predetermined cellular component from a bodily fluid or tissue by centrifugation are provided. More specifically, this invention provides a method for the separation and isolation of one or more components, such as stem cells, buffy coat, bone marrow cells, erythrocytes, leukocytes, thrombocytes, serum, fluorescently labeled cells, and magnetically labeled cells, from whole blood, bone marrow, buffy coat, fat tissue, muscle tissue, and nerve tissue by centrifugation, wherein the components are isolated while the centrifuge is rotating.

Provided are novel vectors and viral vectors capable of expressing exogenous gene or exogenous nucleic acid sequences in a target cell of interest, such as T cells, bone marrow cells, epithelial cells, liver cells and the like. The nucleic acid components of the vectors may include one or more native promoter / enhancer regions having modified sequence segments, one or more non-native promoter / enhancer or non-native promoter's gene or gene segment, and a native viral vector terminator or processing signal or segment thereof. The viral vectors comprise a virus or viral portion having on the surfaces or envelopes adsorption components, one for a packaging cell line and the other for delivery to a target cell. Other viral vectors provided by this invention have two components on their surfaces or envelopes, one of which is native to the virus and the other being non-native and capable of adsorbing to the target cell while being incapable of adsorbing to a native cell for the viral vector. Packaging cell lines for propagating the vectors and viral vectors are also provided, as are novel processes for propagating any of the disclosed vectors or viral vectors.

The present inventors used a model of intrasplenically induced liver metastasis to determine whether or not NF-κB activation in the liver is involved in the onset of metastatic tumors. When IKKβ was deleted from both liver cells and hematopoietically-derived cells, the onset of tumors was reduced remarkably. Tumor cells activated neighboring bone marrow cells (Kupffer cells) and produced mitogens such as interleukin (IL)-6, and this promoted angiogenesis and growth of tumors. The mitogen production depended on NF-κB in hematopoietically-derived Kupffer cells. Furthermore, treatment with an anti-IL-6 receptor antibody decreased the degree of metastatic tumor development. That is, the present inventors showed that tumor metastasis depends on inflammation, and proinflammatory intervention that targets Kupffer cells is useful for chemical prevention of metastatic tumors. Furthermore, it was shown that inhibition of the IKKβ / NF-κB signal transduction pathway, in particular IL-6 inhibition, can be utilized for anti-metastasis agents.

The present inventors discovered that brain-localizing cells exist in the progenitor cell fraction of bone marrow cells. They also elucidated various characteristics of the brain-localizing cells. When these cells are infused into the bloodstream, they circulate in the blood and directly translocate into the cerebral parenchyma from the bloodstream. Furthermore, the present inventors succeeded in developing methods for efficiently preparing brain-localizing cells from bone marrow or bone marrow cells. These methods can be applied to less-invasive regenerative medicines targeting the brain and using autologous cells.

The present invention relates to therapeutic compositions for treating cancer or preventing the growth of cancer cells, e.g., tumor growth, in a subject. The present invention also relates to methods for treating cancer, e.g., inhibiting tumor growth, in a subject who has become resistant to treatment, by administering to a subject an effective amount of a proteasome inhibitor and an effective amount of a therapeutic agent, e.g., a chemotherapeutic agent. The present invention further relates to methods for purging bone marrow, i.e., removing cancer cells from bone marrow, by exposing the bone marrow cells to a proteasome inhibitor and a therapeutic agent, e.g., a chemotherapeutic agent.

A microfracture awl includes an articulating portion that enables the microfracture awl to strike a subchondral bone plate at a precise desired angle to prevent scuffing or undue scraping of the targeted subchondral bone plate. The articulating portion of the microfracture awl is received through a guide sleeve. A proximal end of the articulating portion is rigid and connects to a base. The articulating portion is placed through a guide sleeve and the base resides in a handle attached to the sleeve. The guide sleeve has a curved distal end. The practitioner strikes the rigid base of the microfracture awl and thereby transmits a force to the articulating portion of the awl however, the force is not transmitted to the guide sleeve or handle. Accordingly, the articulating portion of the awl may smoothly travel through the guide sleeve at the angle defined by the curved distal end of the guide sleeve, thereby angularly positioning the tip of the awl with the targeted bone plate. The articulating portion includes a plurality of articulating members configured in a series of ball and socket configurations. A method includes selection of a guide sleeve with the desired curvature and impacting the awl a number of times at the targeted area to produce a desired effect with respect to the release of bone marrow cells to induce growth of fibrocartilage tissue.

The present invention refers to conjugates of erythropoietin with poly(ethylene glycol) comprising an erythropoietin glycoprotein having an N-terminal α-amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have the sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; said glycoprotein being covalently linked to one poly(ethylene glycol) group of the formula—CO—(CH2)x—(OCH2CH2)m—ORwherein the —CO of the poly(ethylene glycol) group forms an amide bond with said N-terminal α-amino group; and wherein R is lower alkyl; x is 2 or 3; and m is from about 450 to about 1350.

The invention provides biologically active erythropoietin (EPO) conjugate compositions wherein EPO is covalently conjugated to a non-antigenic hydrophilic polymer covalently linked to an organic molecule that increases the circulating serum half-life of the composition. The invention thus relates to EPO derivatives described by the formula EPO-(X-Y)N where EPO is erythropoietin or its pharmaceutical acceptable derivatives having biological properties of causing bone marrow cells to increase production of reticulocytes and red blood cells, X is PEG or other water soluble polymers, Y is an organic molecule that increases the circulating half-life of the construct more than the PEG alone and N is an integer from 1 to 15. Other molecules may be included between EPO and X and between X and Y to provide the proper functionality for coupling or valency.

The present invention relates to non-lethal methods of conditioning a recipient for bone marrow transplantation. In particular, it relates to the use of nonlethal doses of total body irradiation, total lymphoid irradiation, cell type-specific or cell marker-specific antibodies, especially antibodies directed to bone marrow stromal cell markers, NK cells, or the CD8 cell marker, cytotoxic drugs, or a combination thereof. The methods of the invention have a wide range of applications, including, but not limited to, the conditioning of an individual for hematopoietic reconstitution by bone marrow transplantation for the treatment of hematologic malignancies, hematologic disorders, autoimmunity, infectious diseases such as acquired immunodeficiency syndrome, and the engraftment of bone marrow cells to induce tolerance for solid organ, tissue and cellular transplantation.

Methods and compositions using E-selectin antagonists are provided for the treatment and prevention of diseases and disorders treatable by inhibiting binding of E-selectin to an E-selectin ligand. Described herein are E-selectin antagonists including, for example, glycomimetic compounds, antibodies, aptamers and peptides that are useful in methods for treatment of cancers, and treatment and prevention of metastasis, inhibiting infiltration of the cancer cells into bone marrow, reducing or inhibiting adhesion of the cancer cells to endothelial cells including cells in bone marrow, and inhibiting thrombus formation.

CD8+ / TCR− bone marrow cells facilitate engraftment of hemapoietic stem cells (HSQ in allogeneic recipients without causing graft versus host disease. The present invention identifies the main subpopulation (55-65%) of CD8+ / TCR− facilitating cells (FQ as plasmacytoid precursor dendritic cells (p-preDC). The present invention notably demonstrates that FC and p-preDC share many phenotypic, morphological, functional features, including IFN-α production, activation and survival after stimulation, and expansion and maturation after FIO-Ligand (FL) treatment. FL mobilized FC, the majority of which express a pre-DC phenotype, facilitate HSC engraftment. Although p-preDC significantly enhance HSC engraftment, they do so with less efficiency than FC. The present invention for the first time defines a direct functional role for p-preDC in HSC engraftment and will have a significant impact on strategies to design effective facilitating cell-based therapies for transplantation.

This invention is directed to an erythropoietin mutein having in vivo biological activity for causing bone marrow cells to increase production of reticulocytes and red blood cells, in that the mutein is N-glycosylated at Asn38 and Asn83 but not N-glycosylated at Asn24. Such muteins have improved pharmaceutical properties.

The invention discloses a method for detecting leukocytes in bone marrow slices based on regional recommendation convolution, which comprises the following steps: performing preprocessing, leukocyte frame selection and leukocyte category labeling, and increasing the number of data sets as a training data set; constructing a regional recommendation convolutional neural network model, taking a ResNet 50 network and an FPN network as a feature extraction network, connecting the output of the FPN network to an RPN network, and allowing the RPN to output a recommendation region to a Faster-RCNN network, and allowing the Faster-RCNN network to output the leukocyte region, and taking the leukocyte category and the category probability corresponding to the leukocyte region as prediction results; training the constructed regional recommendation convolutional neural network model, adjusting parameters until convergence, and obtaining a trained regional recommendation convolutional neural networkmodel; And taking the image of the bone marrow cell slice as input, and outputting a prediction result by the trained regional recommendation convolutional neural network model. The detection methodprovided by the invention is high in leukocyte detection accuracy and precision, and the indexes of the algorithm are measured by the accuracy rate and can reach more than 90%.

The invention discloses an AML (Acute Myelocytic Leukemia) cell segmentation method based on Meanshift cluster and morphological operations. The algorithm is to cluster a bone marrow cell and a cell nucleus from two aspects of spatial distance and color distance, and is combined with a series of morphological operations and the modified watershed conversion technology, so as to solve the accurate segmentation problem of the adherent bone marrow cell and bone marrow cell nucleus. The algorithm is high in stability, and good in robustness for segmenting the adherent bone marrow cells with different AML types under different illumination conditions.

The invention provides a bone marrow cell classification method and classification device based on depth learning, wherein the method comprises the following steps: marking a cell position and a classification tag of bone marrow cells in an image of a bone marrow cell sample; extracting a preset size image block sample with a single classification tag from a bone marrow cell sample image; The convolution neural network of bone marrow cell classification task is constructed, and then the training set composed of image block samples is used to train, and the bone marrow cell classification modelis obtained. The bone marrow cells to be tested image is cut into a plurality of test image blocks with preset size, and the plurality of test image blocks are traversed and input into the bone marrow cells classification model, the bone marrow cells edges in the plurality of test image blocks are detected, and the classification labels corresponding to the bone marrow cells and the classification confidence probabilities are output.

The invention provides a method for obtaining a hemopoietic stem cell by using a three-dimensional induction system. A three-dimensional cell culture medium or cell culture bracket, such as a three-dimensional cell culture system made of the materials such as hydrogel, seaweed and the like is utilized, and / or combined with matrix cells such as bone marrow cell, mouse bone marrow cell lines OP9, OP9DL1 and the like, and / or combined with a plurality of factors including mesoderm induction factors, hematopoietic growth factor and the like to induce multipotent stem cells to differentiate into hemopoietic stem cells. A new method for obtaining the hemopoietic stem cells is built. The system for efficiently inducing the multipotent stem cells to differentiate into the hemopoietic stem cells by using a three-dimensional induction system and / or combining with matrix cells such as bone marrow cell and the like and / or a plurality of factors is built for the first time. Theoretical basis and a technology platform are provided for obtaining clinically available hemopoietic stem cells, and a new method and a new concept are developed for application of hematopoietic cells derived from multipotent stem cells in the fields such as disease mechanism exploration, drug screening and the like.

Methods are provided to manipulate phagocytosis of cells, including hematopoietic cells, e.g. circulating hematopoietic cells, bone marrow cells, etc.; and solid tumor cells. In some embodiments of the invention the circulating cells are hematopoietic stem cells, or hematopoietic progenitor cells, particularly in a transplantation context, where protection from phagocytosis is desirable. In other embodiments the circulating cells are leukemia cells, particularly acute myeloid leukemia (AML), where increased phagocytosis is desirable.

The present invention relates to pharmaceutical compositions for use in inducing proliferation of the hematopoietic system, in particular, of bone marrow cells, comprising a pharmaceutically acceptable carrier, excipient or diluent and, as an active ingredient, an effective amount of an adenosine A1 receptor agonist. The pharmaceutical composition of the present invention may be used to induce proliferation of bone marrow cells, in a variety of clinical situations where such proliferation is therapeutically beneficial.The active ingredient within the pharmaceutical composition of the invention may be a compound of general formula (I) as described herein or any other compound or substance which specifically binds to and / or activates the A1 adenosine receptor and acts as an agonist to the receptor's natural ligand.

A system and method for the percutaneous, autologous transplantation of mesenchymal stem cells and progenitor helper cells (PHC) from bone marrow to degenerated intervertebral discs or joints. This method is designed to be used by operating room staff in a clinical setting to isolate a mesenchymal stem cell population and PHC during the same surgical procedure as transplantation. The method can be used as a two step procedure where cells are harvested, then isolated, then reimplanted at a later time. In addition, experimental techniques are described to determine which bone marrow cells should be removed via negative selection to generate a PHC population most likely to regenerate certain tissue types in-vitro as well as which combination of fibrinogen and hyaluronic acid and which degree of gel maceration provides the best matrix for in-vitro and in-vivo regeneration of joints and intervertebral discs.

Intravenous administration of bone marrow cells collected from rat bone marrow to a rat cerebral infarction model was found to be effective in treating cerebral infarction. Human and murine bone marrow stem cells showed similar effects. Mesenchymal cells such as bone marrow cells, cord blood cells, or peripheral blood cells can be used as agents for in vivo administration against cranial nerve diseases.

The present invention relates to non-lethal methods of conditioning a recipient for bone marrow transplantation. In particular, it relates to the use of nonlethal doses of total body irradiation, total lymphoid irradiation, cell type-specific or cell marker-specific antibodies, especially antibodies directed to bone marrow stromal cell markers or the CD8 cell marker, cytotoxic drugs, or a combination thereof. The methods of the invention have a wide range of applications, including, but not limited to, the conditioning of an individual for hematopoietic reconstitution by bone marrow transplantation for the treatment of hematologic malignancies, hematologic disorders, autoimmunity, infectious diseases such as acquired immunodeficiency syndrome, and the engraftment of bone marrow cells to induce tolerance for solid organ, tissue and cellular transplantation.

The invention discloses an automatic classification method for bone marrow cells. The method comprises the following steps: (1), carrying out saturation-based pre-detection of bone marrow cells; (2),carrying out bone marrow cell detection based on sparse representation; (3), carrying out morphology-based multi-angle bone marrow cell segmentation; (4), carrying out deep-learning-based bone marrowcell classification. According to the invention, an accurate bone marrow cell detection position, an accurate classification image, and an accurate classification result are obtained; no manual participation is needed during the whole process; the full-automatic bone marrow cell detection, segmentation and classification are realized truly; and follow-up medical treatment like acute leukemia diagnosis can be carried out conveniently.

A facility module is provided for producing and storing a cell therapy product comprising: a Cell Therapy (CT) module one including separately prefabricated units having specific functions and separate entrances and exits so as to minimize contamination, and being capable of producing the cell therapy product, and a Banking of Cell and Tissue (BC) module Two including prefabricated units having specific functions and separate entrances and exits so as to minimize contamination, and being capable of appropriately storing hematopoietic stem cells, bone marrow cells and other cells for a prolonged period. It enables easy and low cost production of the cell therapy product, with sufficient quality to be transplanted into patients, within a short period, and permits clinical application to patients expeditiously. The present invention enables convenient installation and use of such a facility module anywhere adequate space is available, by providing the facility in a prefabricated module composed of specialized units according to function.