Abstract: Provided herein are methods for predicting the response of a subject to administration of a glucan prior to said administration, comprising in one embodiment: isolating at least one cell from the subject, wherein the cell is capable of being stimulated by the glucan; contacting the at least one cell with the glucan and incubating for a period of time and under suitable conditions sufficient to stimulate the cell(s) thereby inducing a change in the level of expression, activity and/or secretion of one or more biomarkers from the cell(s); and determining the level of expression and/or secretion of the at least biomarker, wherein the level of expression, activity and/or secretion is predictive of the response of the subject to administration of the glucan.

Abstract: Methods for treating infectious diseases in persons are provided. A person having an infectious disease may be vaccinated with a vaccine designed to induce an immune response against an infectious agent causing the infectious disease. Primed T-lymphocytes are removed from the person and the primed T-lymphocytes are stimulated to differentiate into effector T-lymphocytes in vitro. The effector T-lymphocytes are stimulated to proliferate, in vitro, and the effector T-lymphocytes are infused back into the person.

Abstract: Novel MUC-1 epitopes outside the VNTR region are identified. In addition, the first agonist epitope of MUC-1 is described. The employment of agonist epitopes in peptide, protein and vector-based vaccine may well aid in the development of effective vaccines for a range of human cancers.

Abstract: The present invention discloses a method for increasing the pool of Ngn3+ endocrine progenitor cells obtained from stem cells, by contacting said stem cells with a SUR1/Kir6.2 channel inhibitor. The invention also relates to a method for increasing the mass of pancreatic endocrine cells, in particular of ? cells. The invention further concerns a method for treating diabetes.

Abstract: Described are methods, cell growth substrates, and devices that are useful in preparing cell-containing graft materials for administration to patients. Tubular passages can be defined in cell growth substrates to promote distribution of cells into the substrates. Also described are methods and devices for preparing cell-seeded graft compositions, methods and devices for preconditioning cell growth substrates prior to application of cells, and cell seeded grafts having novel substrates, and uses thereof.

Abstract: Certain embodiments of the invention are directed to methods for inducing an immunologic response to a tumor in a patient using mature dendritic cells transfected with a nucleic acid composition encoding one or more tumor antigens and loaded with a corresponding tumor antigen composition.

Abstract: Methods for treating a bacterial infection in a tissue sample are described. Tissue samples that are harvested from a patient may be infected with bacteria. A rhodamine compound is mixed with the infected tissue sample to form a mixture. The mixture is then exposed to radiant energy to inhibit or kill the bacteria. The exposed mixture is then transplanted into the patient.

Abstract: To control cardiac arrhythmias such as atrial fibrillation post-operatively, various non-ablative agents include polymers, fibroblasts, neurotoxins, and growth factors are introduced into one or more cardiac fat pads into the atrioventricular nodal fat pad in proximity to the autonomic ganglia therein. Any desired technique may be used for introducing the agent, including injection. The sinoatrial nodal fat pad target site and the atrioventricular nodal fat pad target site are identified using a stimulator, which may have electrodes coupled thereto or which may coupled to electrodes built into a delivery system.

Abstract: L-cells may be introduced in the gastrointestinal tract. L-cells are used in the digestive process to produce a more efficient and lasting means of regulating feelings of satiation in a patient. Desired metabolic effects may be achieved by manipulating L-cells via delivery sites, frequency of delivery, or type of biological substance delivered.

Abstract: A method is disclosed for preparing a soft tissue site, and augmenting the soft tissue site, such as the breast(s) of a subject through use of devices that exert a distractive force on the breast(s) and grafting of autologous fat tissue such as domes with sealing rims for surrounding each of the breasts and a regulated pump. The method for preparing the soft tissue site, and enhancing fat graft results, entails application of the distracting force to the targeted soft tissue site for several weeks prior to the graft procedure. A related aspect of the invention includes following the preparation steps by transfer of fat from other areas of the subject to the subject's breast(s), and then reapplication of the distractive force to the breast(s) that received the autologous fat graft. Alternatively, fat from genetically related sources may be used, and the fat may be further processed prior to injection.

Abstract: The invention provides an isolated, purified population of human cells comprising CD8+ T cells with reduced Cbl-b activity. The invention provides uses of such cells in methods for inducing or enhancing an anti-tumor immune response in a subject. These methods comprise: (a) providing a cell population, from a subject or from another source, which comprises CD8+ T cells, (b) reducing Cbl-b activity in the CD8+ T-cells, (c) administering the cells of step (b) to the subject. The invention provides methods for making CD8+ T cells that do not require stimulation through a co-receptor in order for the cell to become activated or proliferated in response to contact via its T cell receptor. Such methods are based upon reducing function of Cbl-b. The invention also provides methods for identifying agents which affect Cbl-b expression or activity.

Abstract: Apparatus and methods are provided for treating an infracted region of myocardium following acute myocardial infarction by reducing the rate of blood flow through infracted region, and then injecting a solution containing stem cells, endothelial progenitor cells or mediators of stem cell mobilization, migration and attachment into the effected region so that the stem cells become embedded therein and promote tissue regeneration. In a first embodiment, delivery of the stem cells, endothelial progenitor cells or mediators of stem cell mobilization, migration and attachment is accomplished using a catheter that relies upon antegrade flow through the coronary artery and a flow control catheter placed in the coronary sinus. In an alternative embodiment, the delivery catheter delivers the stem cells in a retrograde manner through the coronary sinus, and the delivery catheter further comprises an occlusion balloon for controlling outflow through the coronary sinus ostium.

Abstract: A method for treating a facet pain in a subject by providing an effective amount of therapeutic agent in manner that by a biological repair effect on the facet is produced as compared to a temporary anti-inflammatory effect.

Abstract: A method of repairing diseased or dysfunctional organs or of establishing a model system of a disease state is provided. For repairing diseased organs, the method involves engraftment of cells from healthy tissue of the diseased or dysfunctional organ admixed with gel-forming biomaterials and nutrient medium, signaling molecules and extracellular matrix components that can be made insoluble rapidly upon transplantation to form a graft. In this way, the graft mimics the complexity of the native microenvironment with a minimum number of components that allow transplantation of cells to successfully engraft, expand and then rebuild part or the entirety of the diseased or dysfunctional organ. In the case of using grafting methods for establishing a disease model, diseased cells may be transplanted in the biomaterials and into experimental hosts.

Abstract: The first aspect of the present invention is directed to a method of producing a vascular network preform (VNP). This method involves forming a network of elongate fibers and at least one elongate structure from a sacrificial material. The diameter of the elongate structure is greater than that of the elongate fibers. The network of elongate fibers is placed in contact with at least one elongate structure either following or during forming the network of elongate fibers or forming the at least one elongate structure. A matrix is applied around the network of elongate fibers, in contact with the at least one elongate structure. The network of elongate fibers and elongate structure, within the matrix is sacrificed to form a preform. The resulting preform contains a vascular network of fine diameter tubes in contact with at least one elongate passage having a diameter greater than that of the fine diameter tubes. The resulting solid preform and methods of using it are also disclosed.

Abstract: Described herein generally are catheter systems used to deliver cells and other bioactive materials to a target location within the vascular system of the human body, and methods of delivering cells and other bioactive materials to such target locations.

Abstract: The present invention provides a therapeutic approach to maintain and expand HSCs in vivo using currently available medications that target GSK-3 and mTOR. The present invention also provides a system and method for the ex vivo culturing of HSCs, where an mTOR inhibitor is combined with a GSK-3 inhibitor within the culturing conditions.

Abstract: Compositions and methods are provided for repairing damaged avascular zones, including intervertebral disc, in a patient in need thereof.

Abstract: The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. Specifically, the present invention relates to expression of hepsin protease. The detected proteases are themselves specifically over-expressed in certain cancers, and the presence of their genetic precursors may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment.

Abstract: Methods of and apparatus for safely harvesting, processing (i.e. preparing), collecting and re-injecting adipose and other forms of tissue for immediate autologous tissue transplantation, explant culture endeavors or cell dissociations and the like.

Abstract: The present invention relates to a methods, compositions, and admixtures which prevent the aggregation of a population of adipose stromal cells (ASCs), such as an isolated population of adipose stromal cells. In some embodiments, the present invention relates to admixtures and methods of use thereof comprising a population of ASC and a modulator of ASC aggregation. In some embodiments, a modulator of ASC aggregation includes, for example, ionic agents (e.g., heparin), chelating agents (e.g., EDTA), proteolytic agents.(e.g., trypsin or dispase), and agents which inhibit the expression of cell surface receptors and molecules on the surface of ASCs (e.g., inhibitors of integrins expression). In some embodiments, the methods to block ASC aggregation and the admixtures are useful in use of the ASCs to treat various diseases and/or conditions, and increases the safety and/or efficiency of ASCs.

Abstract: Methods and kits for propagating hematopoietic stem cells are provided. The methods comprise culturing cells in medium comprising one or more angiopoietin-like proteins, under conditions sufficient for expansion of HSCs. Angiopoietin-like proteins include angiopoietin-like protein 2, angiopoietin-like protein 3, angiopoietin-like protein 4, angiopoietin-like protein 5, angiopoietin-like protein 7, and microfibrillar-associated glycoprotein (Mfap4). Methods for identifying hematopoietic stem cells are provided and isolated hematopoietic stem cells are also provided.

Abstract: The invention relates to a method of inducing pluripotency in a responsive mammalian cell, which comprises introducing into the cell an effective amount for initiating pluripotency within the cell of Oct4 protein or a functionally equivalent analogue, variant or fragment thereof. The invention also relates to a method of treatment and/or prophylaxis of a degenerative disease or injury in a mammal, which comprises removing from the mammal one or more responsive cells and culturing the cells in a suitable medium, introducing into the cells an effective amount of Oct4 protein or a functionally equivalent analogue, variant or fragment thereof and subsequently returning the cells to the patient. A further aspect of the invention relates to a method of treatment and/or prophylaxis of a degenerative disease or injury in a mammal, which comprises introducing into responsive cells of the patient an effective amount of Oct4 protein or a functionally equivalent analogue, variant or fragment thereof.

Abstract: The invention relates to a method of inducing pluripotency in a responsive mammalian cell, which comprises introducing into the cell an effective amount for initiating pluripotency within the cell of Sox2 protein or a functionally equivalent analogue, variant or fragment thereof. The invention also relates to a method of treatment and/or prophylaxis of a degenerative disease or injury in a mammal, which comprises removing from the mammal one or more responsive cells and culturing the cells in a suitable medium, introducing into the cells an effective amount of Sox2 protein or a functionally equivalent analogue, variant or fragment thereof and subsequently returning the cells to the patient. In a further embodiment the invention relates to a method of treatment and/or prophylaxis of a degenerative disease or injury in a mammal, which comprises introducing into responsive cells of the mammal an effective amount of Sox2 protein or a functionally equivalent analogue, variant or fragment thereof.

Abstract: Described are embodiments that employ ultrasonic energy to selectively lyse larger adipose cells in a suspension containing adipose cells of different sizes resulting in a suspension in which the only viable cells are the small adipose cells and stem cells. Embodiments provide for generating an acoustic standing wave field of sufficient intensity and proper geometry, that high shear stress is induced on the cell membranes of cells larger than a predetermined size. The remaining small adipose cells can be physically separated from the suspension after the suspension is subjected to the acoustic standing wave field.

Abstract: The present invention relates to tumor cell-based vaccines and methods of using same, wherein the vaccines are based on naturally immune privileged tumor cells that have been genetically modified to express MHC-II restricted peptides derived from endogenously encoded tumor antigens, activate CD4+ T-lymphocytes, provide an array of antigens to which the host is not tolerized and/or induce immunity against the originating tumor cells as well as against metastatic tumor cells.

Abstract: The present invention provides devices, small interfering RNAs, and methods for treating a neurodegenerative disorder comprising the steps of surgically implanting a catheter so that a discharge portion of the catheter lies adjacent to a predetermined infusion site in a brain, and discharging through the discharge portion of the catheter a predetermined dosage of at least one substance capable of inhibiting production of at least one neurodegenerative protein. The present invention also provides valuable small interfering RNA vectors, systems, and methods for treating Huntington's disease in vivo without impairment of cell endoplasmic reticulum, spontaneous motor activity, or locomotor activity of a patient.

Abstract: The present invention relates to methods and kits for reducing the occurrence of preterm delivery and other pregnancy-related conditions in pregnant female subjects exhibiting one or more risk factors for preterm delivery and other pregnancy-related conditions. For example, the present invention relates to methods for reducing the occurrence of preterm delivery in a pregnant female subject having no history of preterm delivery and exhibiting one or more risk factors for preterm delivery (e.g., smoking during pregnancy). The methods and kits provide for the administration of a steroid hormone to the pregnant female subject.

Abstract: The present invention provides methods for increasing arterial compliance. The methods generally involve administering to an individual in need thereof an effective amount of relaxin. The present invention further provides methods of increasing arterial compliance in individuals who have Type 1 or Type 2 diabetes. The present invention further provides methods of increasing arterial compliance in perimenopausal, menopausal, and post-menopausal women. The present invention further provides methods of increasing arterial compliance in individuals who have or who are at risk of developing age-associated arterial stiffness.

Abstract: The present invention relates to the use of fucans with a weight-average molar mass of between 5000 and 100 000 g/mol, for the purposes of bone grafting, engineering and regeneration.

Abstract: A method is disclosed for delivering molecules such as pharmaceutical drugs and nucleic acids into skeletal muscle in vivo. The molecule is first injected into the muscle at one or multiple sites. Immediately or shortly after injection, electrodes are placed flanking the injection site and a specific amount of electrical current is passed through the muscle. The electrical current makes the muscle permeable, thus allowing the molecule to enter the cell. In the case where nucleic acid is injected, the efficiency of transfer permits expression of protein encoded by the nucleic acid in an amount that exhibits systemic biological activity and which generates a robust immune response.

Abstract: Methods of generating and expanding human hemangio-colony forming cells and non-engrafting hemangio cells in vitro and methods of expanding and using such cells are disclosed. The methods permit the production of large numbers of hemangio-colony forming cells, non-engrafting hemangio cells as well as derivative cells, such as hematopoietic and endothelial cells. The cells obtained by the methods disclosed may be used for a variety of research, clinical, and therapeutic applications. Human non-engrafting hemangio cells are a novel progenitor cell population that is related to but distinct from the hemangioblast and human hemangio-colony forming cells. The invention also provides compositions, preparations, and solutions comprising hemangio-colony forming cells, non-engrafting hemangio cells or cells differentiated therefrom.

Abstract: A method for delivering particles to a target location of a subject includes slidably disposing a polymeric carrier in a lumen of a catheter. The lumen extends in the catheter from a proximal opening to a delivery region. The method further includes inserting the delivery region of the catheter in the target location of the subject and forcing the particles through the lumen of the catheter to cause the carrier and the particles to exit the delivery region of the catheter. The particles may be cells or drug-loaded microspheres. The carrier can serve to retain the particles in the target location for a period of time. For treatment of vertebral disc degeneration, the particles can be stem cells, the carrier can be formed from collagen, and the target location can be the nucleus pulposus.

Abstract: Compositions that include microthreads are provided. The compositions can be fully or partially encased in a sleeve along at least a portion of their length and can include biological cells and, optionally, therapeutic agents. Also provided are methods for using the compositions to repair or ameliorate damaged or defective tissue, including cardiovascular tissue (e.g., the myocardium).

Abstract: A method for treating or preventing spontaneous preterm birth in pregnant women and improving neonatal morbidity and mortality. The method includes administering to a pregnant woman in need thereof an effective amount of progesterone sufficient to prolong gestation by minimizing the shortening or effacing of her cervix. Treatment and prophylaxis with progesterone in pregnant women having symptoms of short cervix has been clinically shown to increase neonatal health.

Abstract: The present invention relates to a device (2) for cell therapy, said device being designed to be applied on a living tissue and having at least a tight preferably biocompatible first wall (22), designed to form a cavity (24) between said wall and said tissue, and further comprising means (7) to feed a healing substance in said cavity.

Abstract: A method to treat cancer uses ultrapheresis, refined to remove compounds of less than 120,000 daltons molecular weight, followed by administration of replacement fluid, to stimulate the patient's immune system to attack solid tumors. In the preferred embodiment, the patient is ultrapheresed using a capillary tube ultrafilter having a pore size of 0.02 to 0.05 microns, with a molecular weight cutoff of 120,000 daltons, sufficient to filter one blood volume. The preferred replacement fluid is ultrapheresed normal plasma. The patient is preferably treated daily for three weeks, diagnostic tests conducted to verify that there has been shrinkage of the tumors, then the treatment regime is repeated. The treatment is preferably combined with an alternative therapy, for example, treatment with an anti-angiogenic compound, one or more cytokines such as TNF, gamma interferon, or IL-2, or a procoagulant compound. The treatment increases endogenous, local levels of cytokines, such as TNF.

Abstract: The present invention provides fluid and material delivery methods and devices for practicing the methods. The invention provides a method of delivering cellular material comprising injecting the cellular material into a subject such that the injected cells retain their inherent morphologic characteristics upon injection. The method comprises the steps of aspirating the cellular material into a fluid delivery device which incorporates a syringe arrangement. The cellular material is aspirated into the main body of the syringe until the desired amount of a material has filled the syringe body. The needle of the fluid delivery device is then inserted into the skin of a subject at an angle about parallel to the skin until a desired depth has been reached. The cellular material is then injected in the subject until the desired volume of material has been injected. The needle of the device is then rotated approximately 45 to 90 degrees and the needle is removed from the injection site.

Abstract: Methods and systems are disclosed for treating cardiac tissue by delivering a platelet composition which induces neovascularization in the cardiac tissue followed by a cell preparation which induces regeneration in the re-vascularized tissue. The platelet composition can additionally contain structural materials and/or bioactive agents.

Abstract: Apparatus and methods are provided for treating an infarcted region of myocardium following acute myocardial infarction by reducing the rate of blood flow through infarcted region, and then injecting a solution containing stem cells, endothelial progenitor cells or mediators of stem cell mobilization, migration and attachment into the effected region so that the stem cells become embedded therein and promote tissue regeneration. In a first embodiment, delivery of the stem cells, endothelial progenitor cells or mediators of stem cell mobilization, migration and attachment is accomplished using a catheter that relies upon antegrade flow through the coronary artery and a flow control catheter placed in the coronary sinus. In an alternative embodiment, the delivery catheter delivers the stem cells in a retrograde manner through the coronary sinus, and the delivery catheter further comprises an occlusion balloon for controlling outflow through the coronary sinus ostium.

Abstract: The present invention provides fluid and material delivery methods and devices for practicing the methods. The invention provides a method of delivering cellular material comprising injecting the cellular material into a subject such that the injected cells retain their inherent morphologic characteristics upon injection. The method comprises the steps of aspirating the cellular material into a fluid delivery device which incorporates a syringe arrangement. The cellular material is aspirated into the main body of the syringe until the desired amount of a material has filled the syringe body. The needle of the fluid delivery device is then inserted into the skin of a subject at an angle about parallel to the skin until a desired depth has been reached. The cellular material is then injected in the subject until the desired volume of material has been injected. The needle of the device is then rotated approximately 45 to 90 degrees and the needle is removed from the injection site.

Abstract: A method of enhancing the permeability of a biological membrane, including the skin or mucosa of an animal or the outer layer of a plant to a permeant is described utilizing microporation of selected depth and optionally one or more of sonic, electromagnetic, mechanical and thermal energy and a chemical enhancer. Microporation is accomplished to form a micropore of selected depth in the biological membrane and the porated site is contacted with the permeant. Additional permeation enhancement measures may be applied to the site to enhance both the flux rate of the permeant into the organism through the micropores as well as into targeted tissues within the organism.

Abstract: An implantable system which includes a gene/protein delivery device and a pulse generator, as well as method of preparing the gene/protein delivery device and using the system, are provided. In one embodiment, the implantable system detects a predetermined condition or event and, in response, delivers gene(s) and/or protein(s) in conjunction with delivering pacing and/or defibrillation pulses.

Abstract: A method for delivering a cell to a heart of a patient comprises the steps of providing an apparatus for intracardiac drug administration comprising a catheter wherein the catheter has at least one position sensor which generates signals responsive to the position of a catheter and a drug delivery device for delivering the cell. The catheter is inserted into a chamber of the heart at a site and the cell is delivered to the site with the drug delivery device in response to the signals from the position sensor. Typical cells useful for delivery are either myoblasts or myocytes. These cells may be utilized as either an expression vector for promoting angiogenesis or for cell transplantation and fusion through myogenesis.

Abstract: A biologic ventricular assist device that also has the capability to capture, grow, and administer stem cells to regenerate and restore damaged myocardium in the heart. The device works in conjunction with a traditional ventricular assist device and possesses an additional external path or tube that is in-line with the path of the ventricular assist device. The external path allows for the administration of stem cells, genes, genetically modified cells or other therapeutic biologic or pharmacologic agents, as well as leading to a stem cell collecting accessory (14) that captures circulating stem cells. The stem cell collecting accessory is also associated with a chamber (39) for culturing the captured stem cells.

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: Systems and methods that allow the local delivery of stem cells and/or endothelial progenitor cells to a treatment site. More particularly, this disclosure provides cell delivery systems used to induce cell growth and angiogenesis at a treatment site.

Abstract: The present invention provides skin grafting and devices that comprise a systematic approach to the process of skin grafting, i.e., harvesting, post-excision processing and application of donor skin and pre and post-graft treatment of the recipient site.

Abstract: Methods, systems, and devices for of treating intervertebral discs are disclosed. In one embodiment, a minimally invasive method of treating an intervertebral disc is provided. A contrast or imaging media is introduced into a nucleus of the intervertebral disc without removing any of the nucleus. The intervertebral disc is imaged with the contrast media within the nucleus. Then the contrast media is evacuated from the nucleus to reduce intradiscal pressure. Finally, a disc augmentation biomaterial is introduced into the nucleus. The disc augmentation biomaterial is introduced in such a manner that the disc augmentation biomaterial is maintained within the nucleus without having to repair an opening in the annulus surrounding the nucleus.

Abstract: A method of diagnosis and treatment of tumors using High Intensity Focused Ultrasound is provided. The method of diagnosing the presence of a tumor in a patient comprises the steps of subjecting a tumor to high intensity focused ultrasound (HIFU) to cause the tumor cells to release cellular material and evaluating the cellular material for a tumor marker. The method of treating a tumor in a patient can also comprise the step of subjecting a tumor to high intensity focused ultrasound (HIFU) to provoke an immune response.