Abstract: Methods for inducing an immune response to a tumor in a subject are disclosed herein. These methods include selecting a subject with a tumor and administering a therapeutically effective amount of apopototic tumor cells conjugated to a CpG oligodexoynucleotide (ODN) to the subject. In some embodiments, the CpG ODN is a K-type or a D-type CpG ODN. Methods for treating a tumor in a subject are also disclosed herein. These methods include selecting a subject with a tumor and administering a therapeutically effective amount of apopototic tumor cells conjugated to a CpG oligodexoynucleotide (ODN) to the subject. In some embodiments, the tumor cells are autologous. In additional embodiments, the tumor is a lymphoma, cervical cancer, prostate cancer, breast cancer, colon cancer or a lung cancer.

Abstract: Provided are methods of screening to identify molecules capable of binding to CD4 and capable of activating CD4+CD25+ regulatory T cells. Further provided are antibodies and antibody fragments capable of activating CD4+CD25+ regulatory T cells and methods and uses involving the antibodies and fragments thereof.

Abstract: A wound closure apparatus and associated methods are provided which utilize blood fluid by activating the clotting cascade of blood fluid within a substantially enclosed sterile container then introducing the blood fluid to the wound site to complete clotting. An apparatus for providing ways of inhibiting anticoagulating agents and slowing fibrin clot degradation are also disclosed. Kits are also disclosed. The invention provides a clotting cascade initiation apparatus including a substantially enclosed sterile containment chamber within which an aliquot of blood fluid, either autologous or from donor sources, can be received and retained. In preferred embodiments, the sterile containment chamber further includes a heparin binding agent which will bind heparin and remove it from the blood fluid. In further embodiments, the containment chamber will also include a procoagulating agent, wherein a clotting cascade can be initiated when the blood fluid is accepted into the sterile containment chamber.

Abstract: The present invention relates to systems and devices to treat and/or prevent inflammatory conditions within a subject and to related methods. More particularly, the invention relates to systems, devices, and related methods that sequester leukocytes and/or platelets and then inhibit their inflammatory action.

Abstract: Device and method for rapid extraction of body tissue from an enclosed body cavity. Hollow entry cannula with optional core element provides entry into body tissue space such as bone marrow. Aspiration cannula is inserted through cannula into body tissue and is manipulated to advance directionally through body cavity. Optional stylet within aspiration cannula aids in advancing aspiration cannula through body tissue and is removed to facilitate extraction of body tissue through the aspiration cannula. Inlet openings near distal tip of aspiration cannula allow tissue aspiration, with negative pressure source at proximal end of aspiration cannula providing controlled negative pressure. Aspiration cannula may be withdrawn and its path adjusted for multiple entries through the same entry point, following different paths through tissue space for subsequent aspiration of more tissue.

Abstract: A system for applying shear stress ex-situ to a fluid. A method of preparing a fluid for intravenous administration to a patient. In some embodiments, the system comprises a shear device; and at least one device configured for intravenous administration of the fluid to a patient, the devices defining a fluid passage configured to be sterilized and maintained sterile during use, the fluid comprising at least one therapeutic fluid, blood, or a combination thereof. The shear device of the system is in fluid communication with the at least one device configured for intravenous administration of the fluid to a patient.

Abstract: Vascular endothelial growth factor (VEGF) has utility in the treatment of intimal hyperplasia, hypertension and atherosclerosis, and of conditions susceptible to treatment with agents that produce nitric oxide or prostacyclin. Instead of VEGF, an equivalent agent such as an agonist of VEGF receptors may be given, as may nucleic acid encoding such an agonist. The agent may successfully be administered via the adventitial surface of a blood vessel, e.g. using a device which defines a reservoir between the body wall and the vessel's adventitial surface, the reservoir being at least part-filled by a pharmaceutical formulation containing the agent to be delivered.

Abstract: An anti-hemorrhage medication pack for administering an anti-hemorrhage drug, in particular for the treatment of hemorrhage caused by trauma in emergency situations comprises an active ingredient selected from the group comprising the 1-24 amino acid sequence of the adrenocorticotropic hormone (ACTH 1-24) and all its fragments and analogues, and analogues of fragments, with agonist activity on the MC4 melanocortin receptors, and all the synthesis agonists, including those with a nonpeptidic structure, of the MC4 melanocortin receptors. An auto-injector (1; 11) includes the drug for automatically injecting a patient with the drug.

Abstract: A device and methods for the real-time monitoring of stem cells in a stem cell transplant. The device comprises a linear member and particle detection device configured to occupy the lumen of a catheter while the catheter is in place to administer a stem cell transplant to a delivery site in the body of a patient. Monitoring of the stem cells permits the device to provide signals to a computer processor for the determination of one or more characteristics of stem cells in the stem cell transplant.

Abstract: A catheter-based deployment system for deploying cellular material (22) into the heart muscle (25). The deployment system includes a guiding catheter (19) and a needle assembly (31) capable of sliding within the guiding catheter. The needle assembly (31) terminates in a tip (34) having at least one side with an opening (43) in communication with a lumen (20) disposed within the needle assembly (31). Once the guiding catheter (19) is positioned, the needle assembly (31) is advanced until the tip (34) penetrates the muscle wall (25). At a predetermined depth the cellular material (22) may be deployed into the muscle wall (25) via a push rod (46) disposed through the lumen of the needle assembly (31).

Abstract: The present invention relates generally to a method of producing a population of cells and materials for use therewith. More particularly, the present invention is directed to a method of generating the growth of a population of blood-derived cells and materials for use therewith. The method of the present invention facilitates cell growth by virtue of the migration of blood-derived cells from the vasculature of a vascularised receptacle to the acellular tissue support matrix of said receptacle. These findings have now facilitated the design of means for reliably and efficiently deriving cellular populations from blood-derived cells, such as the generation of bone marrow cells including haemopoietic stem cells and mesenchymal stem cells, for use in a wide variety of clinical and research settings.

Abstract: Apparatus and methods for injecting biological agents into tissue. Devices are provided having elongate shafts and distal injection heads for transversely driving needles into tissue and injecting medical agents into the tissue through the needles. A longitudinal force directed along the shaft can be translated to a needle driving force transverse to the shaft. Some devices provide controllably variable needle penetration depth. Devices include mechanical needle drivers utilizing four link pantographs, rack and pinions, and drive yokes for driving a first needle bearing body toward a second tissue contacting body. Other devices include inflatable members for driving and retracting needles. Still other devices include magnets for biasing the needles in extended and/or retracted positions. The invention includes minimally invasive methods for epicardially injecting cardiocyte precursor cells into infarct myocardial tissue.

Abstract: The invention relates to a method of engrafting donor cells into injured myocardium. The method includes delivering donor cells to a delivery site adjacent to and downstream of a chronic total occlusion and treating the chronic total occlusion. The delivery device may be a catheter with a wireguide that may be provided by a retrograde approach via an un-occluded artery or antegrade approach through the chronic total occlusion. The invention also relates to a method of treating injured myocardium and cell compositions for treatment of injured myocardium.

Abstract: The present invention provides a cell transplantation device which is capable of inserting cells for transplantation into a cell-deficient site without application of direct external force to the cells. The present invention discloses a cell transplantation device provided with a plate-type carrier with at least one pass-through hole formed on its side surface, a linear member to be threaded through the pass-through hole, and a pusher member which engages with the linear member that comes out from each exit of the pass-through holes.

Abstract: The invention provides methods for inhibiting cardiomyopathy and for inhibiting cardiac arrhythmia, by administering to an individual in need thereof a cis-epoxyeicosantrienoic acid, an inhibitor of soluble epoxide hydrolase (sEH), or both. In some embodiments, the method comprises administering to the individual a nucleic acid encoding an inhibitor of sEH. Cardiomyopathies treatable by the methods of the invention include cardiac hypertrophy and dilated cardiomyopathy.

Abstract: The present invention includes methods, systems, devices, and apparatus relating to minimizing source-sink mismatch associated with the application of a biological pacemaker in cardiac tissue. Stable and robust pacemaker activity is achieved by the application of the biological pacemaker at more than one site, in a linear pattern.

Abstract: A method and device are herein described to treat a target region of tissue, using at least one energy delivery device coupled to a power source and positioned in a treatment position so as to irreversibly electroporate tissue to ablate a target region, and introduce regenerative materials into a treated region.

Abstract: The invention features devices, systems, and methods for targeted delivery of therapeutic agents in magnetic particle carriers to desired locations on tissue in the body. The systems and methods utilize at least one device comprising a source of magnetization, and at least one device comprising a magnetic or magnetizable material, to facilitate close tissue apposition and sealing, and to facilitate site-specific delivery of magnetic particles comprising therapeutic agents.

Abstract: A warm perfusion system that has the ability to support a tissue or organ at a near normal metabolic rate provides the mechanism not only for restored oxidative metabolism of the organ but for the delivery of cells, cell-based therapeutics, and growth and differentiation factors to a damaged tissue or organ. Subsequent to delivery of therapeutic cells, such as stem cells or progenitor cells, to the damaged organ, the cells can be prompted to grow, multiply and differentiate, thereby restoring damaged tissue.

Abstract: A method, technique and system is disclosed for the delivery of therapeutic agents and/or into the bulk brain tissues and other parts, tissues and organs of the body, including vasculature. A novel form of coaxial catheter provides a means for implanting an outer tube into the brain, then inserting an inner tube into the outer tube and aligning them such that port holes on both of the tubes will overlap and permit a flux of the therapeutic agent to flow into the brain in such a way as to minimize the effects of trapped air, virtually eliminate backflow of the agent, and avoid the potential for additional damage to the brain since only one surgical placement of the outer tube is needed. Similarly, the method, technique system may be utilized to remove fluids or other medium from the brain, tissues, and organs to minimize the effects of escaped air or negative pressure.

Abstract: A process to facilitate growing of cells on a nanotextured percutaneous portal is provided that includes the placement of a nanotextured percutaneous portal partially within a subject. A vacuum manifold is secured to the nanotextured percutaneous portal. Upon coupling the vacuum manifold to a vacuum source, the growth of the cells is facilitated.

Abstract: A medical practitioner can specify certain parameters for a procedure that involves delivering a therapeutic agent, while leaving other parameters open. The therapeutic agent can be sensitive to biomechanical forces (or other influences) associated with delivery. The procedure can involve regenerative medicine, for example delivering progenitor or stem cells to a diseased heart using a catheter, whereby unbridled transport in the catheter may compromise efficacy. The open parameters can influence efficacy of the agent and thus therapeutic outcome. A computer-based system can apply stored information, such as from databases, to narrow the possible values of the open parameters. From the narrowed possibilities, an optimization routine can determine suitable or optimized values for the open parameters. The determined values can manage biomechanical forces incurred by the therapeutic agent, thereby promoting efficacy and healing. The optimized parameters can guide the practitioner in the procedure.

Abstract: The present invention provides for methods of treating a cancer patient. In one methods, cancer cells are harvested from a patient. A therapeutic amount of a rhodamine derivative is then added to the harvested cancer cells. The harvested cells and the rhodamine derivative are then irradiated with a suitable wavelength and intensity for the selective killing of the cancer cells. The irradiated cancer cells are then mixed with antigen presenting cells to form a mixture. The mixture of cancer and antigen presenting cells are then injected into the patient. The present invention also provides for methods of inhibiting or treating an immunological disorder, infection, or a cancer in an individual.

Abstract: Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.

Abstract: The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of soft tissue. Also provided are methods of isolating muscle-derived progenitor cells, and methods of genetically modifying the cells for gene transfer therapy. The invention further provides methods of using compositions comprising muscle-derived progenitor cells for the augmentation and bulking of mammalian, including human, soft tissues in the treatment of various functional conditions, including malformation, injury, weakness, disease, or dysfunction. In particular, the present invention provides treatments and amelioration for urinary incontinence and other urinary tract pathologies.

Abstract: A method of preparing a population of stem cells for autologous implantation to a subject and apparatus used therein are provided. The cells are activated by irradiating the cells with one or more wavelengths of yellow and red and/or green light. In particular, the cells are irradiated with 575-595 nm (5-20 mW), and 630-635 nm or 660-670 nm (10-100 mW) and/or 510-540 nm (10-60 mW) of monochromatic light for 30-60 mins. Preferably the stem cells are adipose-derived stem cells. Therapeutic applications of the activated stem cells are also provided.

Abstract: A nucleic acid is provided which encodes a human TRIM-cyclophilin A fusion sequence encoding a human TRIM-CypA fusion protein which is active as an anti-viral agent, and in particular, as an anti-HIV-1 agent. Also provided is a nucleic acid encoding a polypeptide having both TRIM activity and cyclophilin activity. Also provided is an isolated polynucleotide encoding a human TRIM-CypA fusion protein, or variants thereof retaining the TRIM and cyclophilin A activities. Also provided are compositions thereof, antibodies that specifically bind thereto, and vectors and host cells comprising the nucleic acid or polypeptide. In addition, methods are provided for treating or preventing viral infection, or reducing viral load in a subject comprising administering the nucleic acid, polypeptide, vector, or composition to the subject in an amount effective to treat or prevent the viral infection.

Abstract: Methods and compositions for increasing trichogenicity of cells in culture are provided. One embodiment provides culturing dissociated mammalian dermal cells in vitro in the presence of an effective amount of one or more sonic hedgehog (Shh) pathway agonists to increase the trichogenicity of the dissociated mammalian dermal cells compared to untreated dissociated mammalian dermal cells. The cell culture optionally includes epidermal cells. Preferred Shh agonists include, but are not limited to CUR-0236715 and CUR-0201365 available from Curis, Inc. Trichogenicity is measured using the Aderans Hair Patch Assay™. The cultured dermal cells can be maintained in culture in the presence of the one or more Shh agonists for at least 1 to 7 or more days prior to harvest. The treated, cultured dermal cells can be used to treat hair loss in a mammalian subject, preferably a human, by implanting them in an effective amount to induce hair follicle formation.

Abstract: A physician, nurse, or other healthcare practitioner can deliver a therapeutic agent to a patient in a manner that maintains effectiveness of the therapeutic agent, via monitoring and controlling shear, stress, or other potentially detrimental effect. A gauge, meter, or other monitoring device can provide an indication of shear (or other effect) that the therapeutic agent is experiencing during delivery. The monitoring device can provide information relevant to delivering the therapeutic agent in a manner that maintains effectiveness, thereby guiding the practitioner during delivery. For example, the monitoring device can display an estimate of shear based on sensing flow rate or pressure. The therapeutic agent can comprise one or more therapeutic cells, such as progenitor cells or stem cells, or some other healing substance delivered via a cardiac catheter to the patient's cardiovascular tissue, for example.

Abstract: Described herein are progenitor cancer cells and cell lines isolated from human breast ductal carcinoma in situ (DCIS) lesions and the uses of these cells or cell lines in drug design, drug screening, and monitoring in vivo therapy. The DCIS malignant precursor cells or cell lines are epithelial in origin, are positive for markers of autophagy, show at least one genetic difference from normal cells of said fragment, form 3-D tube-like structures or ball aggregates, or are inhibited in formation of 3-D structures and migration by treatment with chloroquine.

Abstract: The present invention relates to an in vivo method of promoting the growth of autologous cartilage and bone tissue, including tissue that can be explanted to other locations in the subject.

Abstract: The invention provides an isolated or purified nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12. The invention also provides a nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12, wherein the NFAT promoter is located 3? of the nucleotide sequence encoding IL-12. Also provided are related recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. The invention further provides the use of the inventive nucleic acids or related materials in the treatment or prevention of cancer or an infectious disease in a mammal and in the induction of IL-12 expression in a mammal.

Abstract: The invention relates to a method of treating tumor cells within a patient wherein immature dendritic cells developed from the patient's monocyte cells and a lymphocyte cultured medium (LCM) adjuvant are introduced into the patient directly into the patient's tumor cells. The immature dendritic cells and LCM adjuvant combine with the antigens in the tumor cells to form a cancer vaccine, thereby immediately treating the tumor cells of the patient. The invention also provides a precursor treatment step of treating the patient with radiation therapy or a chemotherapy regimen.

Abstract: There is provided a method and use of hematopoietic stem cells for the treatment of various diseases. The differentiation of autologueous hematopoietic stem cells into myeloid lineages is used for reintroduction into a patient in addition to undifferentiated stem cells for the purpose of reconstituting both the defence and long-term engraftment.

Abstract: The present invention is related to a method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 60 (HSP60), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences, and wherein the disease is other than insulin dependent diabetes mellitus (IDDM), thereby treating the disease.

Abstract: The described invention provides methods and regimens for treating adverse consequences of a persistent and progressive myocardial injury-due to a vascular insufficiency that occurs early or late in a subject in need thereof, and progressive myocardial injury-preventing compositions that contain a chemotactic hematopoietic stem cell product, and, optionally, an additional active agent.

Abstract: Multiple myeloma (MM) is a clonal B cell malignancy and remains essentially incurable by conventional anti-tumor therapy. Patients with MM have a median survival of only three years. MM is characterized by proliferation and accumulation of mature plasma cells in the bone marrow (BM) leading to bone destruction, BM failure, anemia, and reduced immune function. The identification of MHC Class I, HLA-A2, associated peptides presented on multiple myeloma cells is an important step in developing immunotherapies for MM. Presented here are methods for creating activated T lymphocytes that are cytotoxic to both peptide loaded T2 target cells and multiple myeloma cell lines.

Abstract: A delivery system is provided that is adapted to treat various urological pelvic disorders, such as prolapse, incontinence, and the like. The delivery system can include at least one biologic loaded or otherwise provided with a bioactive agent. The biologic can comprise any drugs, hormones or steroids, stem cells, growth factors, proteins, and/or other bioactive agents to promote cell or tissue growth for the treatment and strengthening of organ walls or tissue. The biologic is generally adapted to controllably release the agent to the surrounding tissue or organ to provide a local and targeted delivery.

Abstract: Device and method for rapid extraction of body tissue from an enclosed body cavity. Hollow entry cannula with optional core element provides entry into body tissue space such as bone marrow. Aspiration cannula is inserted through cannula into body tissue and is manipulated to advance directionally through body cavity. Optional stylet within aspiration cannula aids in advancing aspiration cannula through body tissue and is removed to facilitate extraction of body tissue through the aspiration cannula. Inlet openings near distal tip of aspiration cannula allow tissue aspiration, with negative pressure source at proximal end of aspiration cannula providing controlled negative pressure. Aspiration cannula may be withdrawn and its path adjusted for multiple entries through the same entry point, following different paths through tissue space for subsequent aspiration of more tissue.

Abstract: A method regenerates specific tissue, preferably mesenchymal tissues like bone, fat, tendon, muscle, cartilage and marrow stroma and hematological tissue (RBC, WBC, platelets, lymphocytes, hematological stem cells (HSC), endothelial progenitor cells (EPC) etc.). A method for reconstructing, regenerating, rejuvenating or reinforcing a damaged or diseased tissue in a mammal subject, and preferably a human patient, uses a (regenerated) tissue obtained by this method.

Abstract: A method is provided for preventing rejection by an immune system of a recipient subject of a tissue transplanted from a donor subject into the recipient subject without the need for long-term administration of non-specific immunosuppressive drugs.

Abstract: TNFR25 compositions enhance the immune response against antigens. Administration of TNFR25 agonists was found to enhance tumor rejection, responses against viral diseases and other infectious organisms.

Abstract: The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of both Prdm1? and C/EBP? activity and/or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of both Prdm1? and C/EBP? expression and/or activity. Further provided are methods for identifying compounds that are capable of modulating both Prdm1? and C/EBP? expression and/or activity.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly prostate cancer, are disclosed. Illustrative compositions comprise one or more prostate-specific polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly prostate cancer.

Abstract: A cell delivery catheter having one of more apearutres is used to positon and deliver cells to an implant site in a patient.

Abstract: Disclosed herein are methods and devices for processing a biomaterial in a closed system and administering the processed biomaterial to a subject.

Abstract: A method of inducing dendritic cell (DC) development by administering Macrophage-Colony Stimulating Factor is provided. M-CSF induces DCs to differentiate into subtypes, for example plasmacytoid DCs and conventional DCs. Induction with M-CSF can be achieved in vitro from hematopoietic precursors, such as bone marrow cells, or in vivo. In vitro, M-CSF-derived DCs can be used to produce cytokines and to stimulate other immune response cells. M-CSF can also be used to induce precursor cells removed from an animal to develop into DCs. In addition, these isolated DCs can be exposed to antigens to stimulate a specific immune response when reintroduced into the animal. Treatments for cancers, such as Acute Myeloid Leukemia, and autoimmune diseases such as Systemic Lupus Erythematosus, are also provided in the invention.

Abstract: Systems, methods, and carriers for percutaneous delivery of growth factors to treat osteonecrosis in the hip and other locations are disclosed. A rolled carrier comprising a biphasic ceramic rolled by a collagen sponge, and carrying a growth factor, are inserted via a delivery tube or cannula into a pre-formed hole in bone without overstuffing of the carrier or growth factor.

Abstract: The present invention includes compositions and methods for increasing the effectiveness of antigen presentation using a DCIR-specific antibody or fragment thereof to which an antigen is attached that forms an antibody-antigen complex, wherein the antigen is processed and presented by a dendritic cell that has been contacted with the antibody-antigen complex.

Abstract: Micro-organ cultures which include isolated populations of cells having specific characteristics are described. Salient features of the subject micro-organ cultures include the ability to be maintained in culture for relatively long periods of time, as well as the preservation of an organ microarchitecture which facilitates, for example, cell-cell and cell-matrix interactions analogous to those occurring in the source organ. The micro-organ cultures of the invention can be used in methods for delivering gene products to recipient subjects, for identifying cell proliferative and cell differentiating agents, and identification and isolation of progenitor and stem cells. In addition, the micro-organ cultures of the present invention can be used in methods for identifying inhibitors of cell proliferation, cell differentiation and viral infectivity. In other embodiments, the micro-organ cultures can be used for transplantation.