866 results about "Osteocyte" patented technology

The present invention relates to methods for stimulating osteoblast proliferation and methods for selecting pharmacologically active compounds useful for stimulating osteoblast proliferation.

The present invention relates to a method of producing osteocyte cell line in various stages of differentiation. Such cell line remains stable after more than 20 passages. The osteocyte has a stellate shape with dendritic processes and expresses high level of osteocalcin. More specifically, it provides a method of production for cultured osteocytes of various differentiation stages. Furthermore, it relates to osteocyte cell line, and more specifically cultured osteocyte. The invention also relates to a method for the production of monoclonal antibodies using such cultured osteocytes and further relates to hybridomas and monoclonal antibodies which recognize an osteocyte-specific antigen. Finally, the invention relates to a method of screening for modification factors and binding factors for osteocytes.

The present invention provides methods of improving the osteogenic and / or chondrogenic activity of a bone matrix, e.g., a dermineralized bone matrix (DBM), by exposing the bone matrix to one or more treatments or conditions. In preferred embodiments the bone matrix is derived from human bone. The treatment or condition may alter the structure of the bone matrix and / or cleave one or more specific proteins. Cleavage may generate peptides or protein fragments that have osteoinductive, osteogenic, or chondrogenic activity. Preferred treatments include collagenase and various other proteases. The invention further provides improved bone and cartilage matrix compositions that have been prepared according to the inventive methods and methods of treatment using the compositions. The invention further provides methods of preparing, testing, and using the improved bone matrix compositions. Ona assay comprises exposing relatively undifferentiated mesenchymal cells to a bone matrix composition and measuring expression of a marker characteristic of osteoblast or chondrocyte lineage(s). Increased expression of the marker relative to the level of the marker in cells that have been exposed to a control matrix (e.g., an inactivated or untreated matrix) indicates that the treatment or condition increased the osteogenic and / or chondrogenic activity of the bone matrix. Suitable cells include C2C12 cells. A suitable marker is alkaline phosphatase. The inventive methods increase the osteogenic and / or chondrogenic activity of human DBM when tested using this assay system.

The present invention relates to pharmacologically active compounds which are capable of binding to nuclear hormone receptors and are useful for the stimulation of osteoblast proliferation and ultimately bone growth. This invention also relates to the use of such compounds for the treatment or prevention of diseases and / or disorders associated with nuclear hormone receptor families.

The invention is directed to a method of inhibiting bone resorption. The method comprises administering to a human an amount of sclerostin inhibitor that reduces a bone resorption marker level for at least 2 weeks. The invention also provides a method of monitoring anti-sclerostin therapy comprising measuring one or more bone resorption marker levels, administering a sclerostin binding agent, then measuring the bone resorption marker levels. Also provided is a method of increasing bone mineral density; a method of ameliorating the effects of an osteoclast-related disorder; a method of treating a bone-related disorder by maintaining bone density; and a method of treating a bone-related disorder in a human suffering from or at risk of hypocalcemia or hypercalcemia, a human in which treatment with a parathyroid hormone or analog thereof is contraindicated, or a human in which treatment with a bisphosphonate is contraindicated.

Oral dosage forms of osteoclast inhibitors, such as nitrogen-containing bisphosphonates, can be used to treat or alleviate pain or related conditions.

Three-dimensional tissue-like organization of cells by high cell-seeding-density culture termed as macromass culture is described. By macromass culture, cells can be made to organize themselves into a tissue-like form without the aid of a scaffold and three-dimensional macroscopic tissue-like constructs can be made wholly from cells. Tissue-like organization and macroscopic tissue-like constructs can be generated from fibroblastic cells of mesenchymal origin (at least), which can be either differentiated cells or multipotent adult stem cells. In this work, tissue-like organization and macroscopic tissue-like constructs have been generated from dermal fibroblasts, adipose stromal cells-derived osteogenic cells, chondrocytes, and from osteoblasts. The factor causing macroscopic tissue formation is large scale culture at high cell seeding density per unit area or three-dimensional space, that is, macromass culture done on a large scale. No scaffold or extraneous matrix is used for tissue generation, the tissues are of completely cellular origin. No other agents (except high cell-seeding-density) that aid in tissue formation such as tissue-inducing chemicals, tissue-inducing growth factors, substratum with special properties, rotational culture, etc, are employed for tissue formation. These tissue-like masses have the potential for use as tissue replacements in the human body. Tissue-like organization by high cell-seeding-density macromass culture can also be generated at the microscopic level.

The present invention is directed to a non-isotopic methods for the in vitro and in vivo detection of hydroxyapatite-positive cells and structures.

The present invention relates to methods and materials for in vivo repair of cartilage or bone and cartilage defects in mammals. The invention relates to membranes carrying a composition comprising at least one stimulation molecule, which is capable of inducing signal transduction in chondroblasts / chondrocytes and / or osteoblasts / osteocytes. Furthermore the invention relates to a method for the preparation of chondroblasts / chondrocytes and / or osteoblasts / osteocytes suspensions.

The invention discloses a health product for increasing bone density and a preparation method of the health product. Chinese dwarf cherries, Chinese herbal medicine extracts refined by adopting a modern extraction technology and other raw materials having the function of increasing the bone density are scientifically compounded and are scientifically combined omnibearingly to play a synergistic effect, so as to effectively promote the calcium absorption in multiple aspects, repair and reconstruct the cartilago articularis, promote the generation of synovial fluid, promote the synthesis of collagen in cartilago articularis substrates, prevent the further degradation of cartilage, indirectly reduce the osteoclast function, inhibit the re-absorption of bones, increase the content of bone calcium and perfect the biomechanical properties of the bones, so that the product has a good function of increasing the bone density. A microwave drying technology in the preparation method can be used for further improving the integration and biological stability of the health product, and by means of the antioxidant activity of a grape seed extract in the raw materials, the strong adsorption and inclusion functions of modified dietary fibers and the antifungal propertie of the Chinese herbal medicine extracts, an efficient, safe, nutritional and stable health product having the function of increasing the bone density is prepared finally.

The invention discloses a serum-free medium for culturing placenta mesenchymal stem cells. The serum-free medium takes a DMEM (Dulbecco Modified Eagle Medium) culture solution as a basis and also contains a fibroblast growth factor receptor 2, growth hormone, insulin, transferrin, glutathione, BMP-4, L-glutamine, sodium pyruvate, non-essential amino acids and beta-mercaptoethanol. According to various serum-free media provided by the invention, growth and proliferation of the placenta mesenchymal stem cells in a serum-free medium system can be effectively promoted, the placenta mesenchymal stem cells have higher growth and proliferation rate in the serum-free medium system compared with a serum cell culture medium, the characteristics of the stem cells are preserved, the serum-free medium has multiple differential potentials, and the stem cells can be directionally induced into fat cells and osteoblasts.

The present invention proposes formative agent of protein complex, in which a polyphenol is useful component, and the agent is useful as gene complex, cell adhesion inhibitor or immune tolerogen. The polyphenol of forming the agent is selected from catechin group consisting of epigallocatechin-gallate, tannic acids, or proanto-dianisidine, a protein of the protein complex is selected from proteins consisting of animal proteins composed of polypeptide chain of peptide-combined amino acids, vegetative proteins, nucleus proteins, glycogen proteins, lipo-proteins and metal proteins, the gene complex comprises by compositing genes by polyphenol catechins in order to introduce genes to cells of animals or human bodies, a cell composed of the cell adhesion inhibitor is selected from cells consisting of an animal cell including a stem cell, skin cell, mucosa cell, hepatocyte, islet cell, neural cell, cartilage cell, endothelial cell, epidermal cell, osteocyte or muscle cell isolated from human or animal organism, or sperm, ovum or fertilized egg of domestic animals or fishes and a tissue or an organ for transplantation of the immune tolerogen is selected from the tissue or the organ consisting of skin, blood vessel, cornea, kidney, heart, liver, umbilical cord, bowels, nerve, lung, placenta or pancreas.

A method of generating cultured chondrocytes / endochondral bone cells is disclosed. The method comprises isolating chondrocytes from mandibular condyle tissue, and culturing said isolated chondrocytes.

It is intended to provide a pluripotent cell having the following properties: (1) being contained in a mixed-cell type population obtained by enzymatic treatment of the tissue collected from an animal; (2) being contained in a sedimented cell population obtained by centrifugating the mixed-cell type population of the property (1); (3) selectively proliferating by culturing in a medium containing 2% (v / v) or lower serum and 1 to 100 ng / ml of fibroblast growth factor-2; and (4) being differentiated into cells having the characteristics of adipocytes, osteoblasts, chondrocytes, tendon cells, myocardial cells, myoblasts, neurocytes or vascular endothelial cells by adjusting the culture condition; cells having differentiated from the above cell; and a method of conveniently obtaining the pluripotent cell in a large amount.

This invention relates to human adipose tissue-derived multipotent adult stem cells. More particularly, the invention relates to human adipose tissue-derived multipotent stem cells, which can be maintained in an undifferentiated state for a long period of time by forming spheres and have high proliferation rates, as well as methods for isolating and maintaining the adult stem cells, and methods for differentiating the multipotent adult stem cells into nerve cells, fat cells, cartilage cells, osteogenic cells and insulin-releasing pancreatic beta-cells. Also, the invention relates to cellular therapeutic agents for treating osteoarthritis, osteoporosis and diabetes and for forming breast tissue, which contain the differentiated cells or the adult stem cells. Although the multipotent stem cells are adult stem cells, they have the ability to differentiate into osteogenic cells, nerve cells, astrocytes, fat cells, chrondrogenic cells or insulin-releasing pancreatic beta-cells, and so are effective in treating osteoporosis, osteoarthritis, nerve disease, diabetes, etc. Also, the stem cells form spheres in a serum-free medium containing CORM-2, and thus can be maintained in an undifferentiated state for a long period of time. Also, the stem cells have very high proliferation rates. Accordingly, the stem cells are useful as cellular therapeutic agents.

The invention is in the field of methods for medical treatment. It provides an improved method for repairing damaged cartilage and / or preventing cartilage degeneration in tissue, in particular in a joint by administering a pharmaceutically active agent directly into the fat pad of a joint. The pharmaceutically active agent is preferably selected from the group consisting of agents that stimulate chondrogenic differentiation and / or cartilage matrix synthesis; agents that inhibit osteogenesis and / or hypertrophy, anti-inflammatory agents, agents that inhibit apoptosis of chondrocytes, agents that inhibit senescence of chondrocytes and agents that enhance lubrication of a joint.

This invention relates to human adipose tissue-derived multipotent adult stem cells. More particularly, the invention relates to human adipose tissue-derived multipotent stem cells, which can be maintained in an undifferentiated state for a long period of time by forming spheres and have high proliferation rates, as well as methods for isolating and maintaining the adult stem cells, and methods for differentiating the multipotent adult stem cells into nerve cells, fat cells, cartilage cells, osteogenic cells and insulin-releasing pancreatic beta-cells. Also, the invention relates to cellular therapeutic agents for treating osteoarthritis, osteoporosis and diabetes and for forming breast tissue, which contain the differentiated cells or the adult stem cells. Although the multipotent stem cells are adult stem cells, they have the ability to differentiate into osteogenic cells, nerve cells, astrocytes, fat cells, chrondrogenic cells or insulin-releasing pancreatic beta-cells, and so are effective in treating osteoporosis, osteoarthritis, nerve disease, diabetes, etc. Also, the stem cells form spheres in a serum-free medium containing CORM-2, and thus can be maintained in an undifferentiated state for a long period of time. Also, the stem cells have very high proliferation rates. Accordingly, the stem cells are useful as cellular therapeutic agents.

Methods and devices are described for the regulation of Transforming Growth actor (TGF)-β1, β2, and / or β3 protein gene expression in bone cells and other tissues via the capacitive coupling or inductive coupling of specific and selective electric fields to the bone cells or other tissues, where the specific and selective electric fields are generated by application of specific and selective electric and electromagnetic signals to electrodes or one or more coils or other field generating device disposed with respect to the bone cells or other tissues so as to facilitate the treatment of diseased or injured bone and other tissues. By gene expression is meant the up-regulation or down-regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased bone and other tissue that include generating specific and selective electric and electromagnetic signals that generate fields in the target tissue optimized for increase of TGF-β1, β2, and / or β3 protein gene expression and exposing bone and other tissue to the fields generated by specific and selective signals so as to regulate TGF-β1, β2, and / or β3 protein gene expression in such tissue. The resulting methods and devices are useful for the targeted treatment of bone fractures, fractures at risk, delayed unions, nonunion of fractures, bone defects, spine fusions, osteonecrosis or avascular necrosis, as an adjunct to other therapies in the treatment of one or all of the above, in the treatment of osteoporosis, and in other conditions in which TGF-β1, β2, and / or β3 protein may be implicated.

The present invention provides isolated pluri-differentiated human mesenchymal progenitor cells (MPCs), which simultaneously express a plurality of genes that are markers for multiple cell lineages, wherein the multiple cell lineages comprise at least four different mesenchymal cell lineages (e.g., adipocyte, osteoblast, fibroblast, and muscle cell) and wherein each of the markers is specific for a single cell lineage. The present invention also method for isolating and purifying human mesenchymal progenitor cells from Dexter-type cultures for characterization of and uses, particularly therapeutic uses for such cells. Specifically, isolated MPCs can be used for diagnostic purposes, to enhance the engraftment of hematopoietic progenitor cells, enhance bone marrow transplantation, or aid in the treatment or prevention of graft versus host disease.

Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

This invention relates, in part, to unique and newly identified genetic polynucleotides involved in the process of bone remodeling; variants and derivatives of the polynucleotides and corresponding polypeptides; uses of the polynucleotides, polypeptides, variants and derivatives; and methods and compositions for the amelioration of symptoms caused by bone remodeling disorders. Disclosed in particular are, the isolation and identification of polynucleotides, polypeptides, variants and derivatives involved in osteoclast activity, validation of the identified polynucleotides for their potential as therapeutic targets and use of the polynucleotides, polypeptides, variants and derivatives for the amelioration of disease states and research purposes.

The present invention discloses osteogenic and anti-adipogenic oxysterols. Agents and methods for protecting, blocking or rescuing marrow stromal cells from the inhibitory effects of oxidative stress on their osteoblastic cellular differentiation are disclosed. Exemplary agents include oxysterols alone or in synergistic combinations, as well as hedgehog or Wnt signaling activators. The synergistic effects of oxysterols and bone morphogenic proteins are also disclosed.

Scaffolds made of composite materials and uses thereof in the field of biomedical engineering are disclosed, wherein the composite materials comprise bioactive microparticles that could induce the human bone tissue to regenerate. The scaffolds uses the combination of silicon, calcium, and phosphorus microparticles as bioactive substance that could actively induce the human osteoblasts to proliferate and differentiate, promote the formation and calcification of new bone. Furthermore, the scaffolds employs organic polymer as carrier, takes a three-dimensional structure and external anatomical shape, and exhibits several characteristics compatible with the regeneration of bones and the neogenesis of blood vessels, thereby it could be used safely, economically and effectively for repairing the defect of bone tissue as well as in orthopedic operation of human bone. The present invention also discloses the methods for preparing the scaffolds.

The invention discloses a method for preparing a bioactive poly (lactic-co-glycolic acid) / collagen / hydroxyapatite composite fiber membrane for bone repair. The method comprises the following steps of: treating a poly (lactic-co-glycolic acid) electrospun nanofiber membrane by using plasma, coating collagen, and immersing the poly (lactic-co-glycolic acid) electrospun nanofiber membrane into a simulated human physiologic body fluid to mineralize to obtain the poly (lactic-co-glycolic acid) / collagen / hydroxyapatite composite fiber membrane. The preparation method of the invention has the advantages of simpleness, high speed and wide material sources. By adopting the method of plasma treatment and coating, the highly-bionic nanofiber composite membrane is prepared by the steps of introducing collagen with osteocyte epimatrix into the poly (lactic-co-glycolic acid) electrospun nanofiber membrane and depositing active hydroxyapatite onto the fiber membrane, thereby obtaining. The composite fiber membrane has the advantages of favorable combination properties and convenient operation, can effectively promote the capabilities of adherence, growth and calcification osteogenesis of osteoblasts and stem cells, and is hopeful to become an ideal active bracket for bone repair.

The present invention concerns methods for the ex vivo formation of mammalian bone and subsequent uses of the bone. A critical and distinguishing feature of the present invention are defined tissue culture conditions and factors resulting in the formation of bone cell spheroids. The invention also provides for methods of implanting into subjects the ex vivo formed bone. Also described are methods for genetically altering the bone cell spheroids to affect bone formation, identification of candidate modulators of bone formation, and identification of genes involved in bone formation.

A novel protein which binds to Osteoclastogenesis Inhibitory Factor (OCIF-binding molecule; OBM), a process for preparing the same, DNA encoding said protein, a protein having an amino acid sequence encoded by this DNA, a method for producing said protein by genetic engineering technique, and a pharmaceutical composition containing said protein. Screening methods for a substance for controlling expression of said protein using said protein and the DNA, a substance which inhibits or modulates the biological activity of said protein, or a receptor which transmits the action of said protein through binding to said protein, the substance obtained by the screening methods, and a pharmaceutical composition which contains this substance. An antibody for said protein, a process for preparing the same, a measuring method of said protein using the antibody, and a medicine comprising this antibody.

Methods and devices for the regulation of matrix metalloproteinase gene expression in cartilage cells via the application of fields generated by specific and selective electric and electromagnetic signals in the treatment of diseased or injured articular cartilage. By gene expression is meant the up-regulation or down-regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased cartilage tissue that include generating specific and selective electric and electromagnetic signals that generate fields optimized for reduction of matrix metalloproteinase gene expression and exposing cartilage tissue to the fields generated by specific and selective signals so as to regulate matrix metalloproteinase gene expression in such cartilage tissue. The resulting methods and devices are useful for the targeted treatment of osteoarthritis, rheumatoid arthritis, cartilage injury, cartilage defects, and tumor metastasis.

Methods for obtaining osteoprogenitors, osteoblasts or osteoblast phenotype cells, as well as cell populations including such cells, from human bone marrow stem cells in vitro or ex vivo are disclosed. Bone marrow stem cells are contacted with human serum or plasma and a growth factor or a biologically active variant or derivative thereof. In addition, osteoprogenitor, osteoblast or osteoblast phenotype cell types and cell populations are provided. The cell populations may include additional cell types, such as endothelial cells or progenitors. The osteoprogenitors, osteoblasts or osteoblast phenotype cells may be used in therapy, particularly bone therapy.

Disclosed herein is a matrix for inducing or enhancing osteoclast differentiation. The matrix comprises a material having an osteoclastogenic agent associated therewith, the agent being releasable from the material in an amount which is sufficient to induce or enhance osteoclast differentiation.