Abstract: Disclosed are medicaments and methods for inhibiting brain inflammation and the cognitive memory loss attendant brain disease and damage in an animal. Status epilepticus, stroke and Alzheimer's disease are particular pathologies that are treated employing pharmaceutically acceptable preparations of the A1 exosomes. The preparations comprise an enriched population of A1 exosomes, such as exosomes derived from culture medium from mesenchymal stem cells. Medicaments and methods for inhibiting pattern recognition and/or memory impairment attendant a brain injury event or degenerative brain disease are also disclosed, comprising administering a pharmaceutically acceptable preparation of exosomes, particularly A1 exosomes, that are CD9? and that prevent the elevation of pro-inflammatory cytokines attendant a brain injury or disease.

Abstract: Preparations comprising an enriched population of extracellular vesicles (nEVs) having a negatively charged surface, and that are CD81+ and CD9?, are provided. Improved processes and methods for producing an enriched population of nEVs from non-murine cells, especially human origin cells and/or tissues, are disclosed. Therapeutic methods for using the preparations, including for reducing brain inflammation and treatment of various pathologies associated with brain inflammation, such as by intravenous or intranasal administration, are also described. Methods and preparations for reducing brain inflammation associated with traumatic brain injury (TBI) are also disclosed. A method for treating a patient having suffered a mild traumatic injury (mTMI), or concussion, such as a sports-related head injury, is also disclosed. The nEVs are also demonstrated to reduce the expression level of IL-I? in brain tissue of an animal having had traumatic brain injury.

Abstract: Preparations comprising an enriched population of extracellular vesicles (nEVs) having a negatively charged surface, and that are CD81+ and CD9?, are provided. Improved processes and methods for producing an enriched population of nEVs from non-murine cells, especially human origin cells and/or tissues, are disclosed. Therapeutic methods for using the preparations, including for reducing brain inflammation and treatment of various pathologies associated with brain inflammation, such as by intravenous or intranasal administration, are also described. Methods and preparations for reducing brain inflammation associated with traumatic brain injury (TBI) are also disclosed. A method for treating a patient having suffered a mild traumatic injury (mTMI), or concussion, such as a sports-related head injury, is also disclosed. The nEVs are also demonstrated to reduce the expression level of IL-I? in brain tissue of an animal having had traumatic brain injury.

Abstract: A method of producing mesenchymal stem cells from induced pluripotent stem cells in which induced pluripotent stem cells are cultured in the presence of a TGF-? inhibitor an in an atmosphere containing from about 7 vol. % to about 8 vol. % CO2 for a period of time from about 20 day to about 35 days. The cells then are transferred to a culture dish having a hydrophilic surface, and the cells are cultured in a medium containing a TGF-? inhibitor for a period of time sufficient to produce mesenchymal stem cells. Such mesenchymal stem cells are more stable and less likely to form tumors, cancers, or teratomas. Also, the induced pluripotent stem cells may be genetically engineered with at least one polynucleotide encoding a therapeutic agent and then are cultured as hereinabove described to provide genetically engineered mesenchymal stem cells that express sustained amounts of a biologically active protein or polypeptide.

Abstract: Pharmaceutically acceptable preparations of extracellular vesicles derived from activated MSCs are provided. These preparations are essentially free of MSCs, and demonstrate anti-inflammatory inhibiting pharmacological activity in vivo. Methods for using the preparations to prevent the onset of autoimmune diseases are presented. The MSC derived extracellular vesicles are provided in pharmaceutically acceptable preparations with a carrier, such as saline, and may be used to inhibit activation of antigen presenting cells. These preparations may also be used to suppress the development of T helper 1 (Th1) and Th17 cells. The disclosed activated MSC-derived extracellular vesicle preparations are essentially free of MSCs and other cells.

Abstract: Isolated mesenchymal stem cells, which produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount of at least a first preselected amount, or produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount that does not exceed a second preselected amount, as determined by an assay, such as a RT-PCR assay. Isolated mesenchymal stem cells that produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount of at least the first preselected amount are useful in treating diseases, conditions, and disorders associated with inflammation, while isolated mesenchymal stem cells that produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount that does not exceed the second preselected amount are useful in treating bone diseases, conditions, and disorders, including bone injuries.

Abstract: Preparations comprising an enriched population of extracellular vesicles (nEVs) having a negatively charged surface, and that are CD81+ and CD9?, are provided. Improved processes and methods for producing an enriched population of nEVs from non-murine cells, especially human origin cells and/or tissues, are disclosed. Therapeutic methods for using the preparations, including for reducing brain inflammation and treatment of various pathologies associated with brain inflammation, such as by intravenous or intranasal administration, are also described. Methods and preparations for reducing brain inflammation associated with traumatic brain injury (TBI) are also disclosed. A method for treating a patient having suffered a mild traumatic injury (mTMI), or concussion, such as a sports-related head injury, is also disclosed. The nEVs are also demonstrated to reduce the expression level of IL-I? in brain tissue of an animal having had traumatic brain injury.

Abstract: The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal.

Abstract: The present invention provides compositions comprising mesenchymal stem cells (MSCs), and methods for their novel use in the repair of cardiac damage and treatment of inflammatory diseases. The invention also provides methods for using TSG-6 protein that is secreted by MSCs under certain conditions, for repair of cardiac damage and inflammatory disease. The compositions of the invention may be particularly useful in restoring cardiac function following cardiac damage, including, but not limited to, myocardial infarction, as well as in reducing symptoms of inflammatory disease.

Abstract: The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal.

Abstract: The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal.

Abstract: Isolated mesenchymal stem cells, which produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount of at least a first preselected amount, or produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount that does not exceed a second preselected amount, as determined by an assay, such as a RT-PCR assay. Isolated mesenchymal stem cells that produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount of at least the first preselected amount are useful in treating diseases, conditions, and disorders associated with inflammation, while isolated mesenchymal stem cells that produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount that does not exceed the second preselected amount are useful in treating bone diseases, conditions, and disorders, including bone injuries.

Abstract: A method of treating or preventing a gum disease or gum disorder or gum injury in a mammal by administering to the mammal at least one inflammation modulatory or anti-inflammatory protein or polypeptide, such as TSG-6 protein, or a biologically active fragment, derivative, or analogue thereof. Gum diseases or gum disorders or gum injuries that may be treated include periodontal gum disease, and gum wounds resulting from gum surgeries.

Abstract: A method of producing mesenchymal stem cells from induced pluripotent stem cells in which induced pluripotent stem cells are cultured in the presence of a TGF-?inhibitor an in an atmosphere containing from about 7 vol. % to about 8 vol. % C02 for a period of time from about 20 day to about 35 days. The cells then are transfered to a culture dish having a hydrophilic sur face, and the cells are cultured in a medium containing a TGF-? inhibitor for a period of time sufficient to produce mesenchymal stem cells. Such mesenchymal stem cells are more stable and less likely to form tumors, cancers, or teratomas. Also, the induced pluripotent stem cells may be genetically engineered with at least one polynucleotide encoding a therapeutic agent and then are cultured as hereinabove described to provide genetically engineered mesenchymal stem cells that express sustained amounts of a biologically active protein or polypeptide.

Abstract: The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal.

Abstract: The present invention encompasses an osteogenic composition comprising mesenchymal stem cells pre-cultured in the presence of an agent that accelerates canonical Wnt signaling therein. Also, provided are osteogenic compositions incorporated into a biocompatible gel. The present invention provides methods for treating bone degeneration or injury associated with a pathophysiological condition in a mammal or for accelerating repair of a skeletal injury in a mammal by administering to the mammal or contacting the site of injury with the osteogenic composition.

Abstract: The present invention encompasses methods, compositions, and devices for treating an ocular disease, disorder or condition in a mammal. The invention includes polypeptides that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties, and their application in the treatment of eye disease, particularly diseases of the retina. In particular aspects, the invention includes administration of a therapeutic polypeptide such as a stanniocalcin family member protein for the treatment of an eye disease. Also included are fusion proteins and cells stimulated or modified to express the therapeutic polypeptides as set forth herein.

Abstract: A method of treating or preventing a gum disease or gum disorder or gum injury in a mammal by administering to the mammal at least one inflammation modulatory or anti-inflammatory protein or polypeptide, such as TSG-6 protein, or a biologically active fragment, derivative, or analogue thereof. Gum diseases or gum disorders or gum injuries that may be treated include periodontal gum disease, and gum wounds resulting from gum surgeries.

Abstract: A method of producing a protein or polypeptide, such as, for example, TSG-6 protein, or a biologically active fragment, derivative or analogue thereof, by introducing into mammalian cells a polynucleotide encoding the biologically active protein or polypeptide or biologically active fragment, derivative, or analogue thereof. The cells then are suspended in a protein-free medium that includes at least one agent that suppresses production of hyaluronic acid, hyaluronan, or a salt thereof by the cells. The cells are cultured for a time sufficient to express the biologically active protein or polypeptide or biologically active fragment, derivative or analogue thereof. The biologically active protein or polypeptide, or fragment, derivative, or analogue thereof then is recovered from the cells, such as, for example, by recovering the protein or polypeptide secreted by the cells from the cell culture medium.

Abstract: The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal.