Abstract: The present invention relates to novel cell (e.g., hepatocyte, etc.) compositions and methods for their preparation and use. In particular, the invention concerns methods of processing preparations of such cells so as to permit their repeated cryopreservation and thawing while retaining substantial viability. The invention also concerns preparations of cells (e.g., hepatocytes) that have been repeatedly cryopreserved and thawed.

Abstract: The present invention aims to freeze and store organs or tissues taken from human bodies or animals and after thawing, use the resulting organs or tissues, or cells taken and extracted therefrom for medical treatment. The present invention is characterized in that the organs or tissues taken from human bodies or animals are regenerated through the steps of freezing, storing and thawing; the cells taken from the organs or tissues undergo cell division and colonization.

Abstract: A corneal storage solution which maintains cell density and cell viability of corneas stored in vitro for a period of greater than four days up to about two weeks is provided. The solution contains a buffered, balanced, nutrient and electrolyte aqueous solution, at least one colloidal osmotic agent, a phenolic antioxidant compound, a non-lactate-generating substrate, a thiol-containing compound, insulin, and at least one antibiotic. A method for in vitro storage and preservation of the viability of human corneal endothelial cells for subsequent use includes the steps of removing a cornea from an eye globe and placing the cornea in the above corneal storage solution.

Abstract: A method for promoting expression of a heat shock protein, or for inhibiting cell injury or cell death, or for treating a disease for which cell or tissue protection is desired, or for promoting production of IL-10, or for inhibiting production of IL-8, by administering an effective amount of a fraction containing a hyaluronic acid tetrasaccharide comprising four saccharide residues and having certain physicochemical properties or by administering an effective amount of an isolated and substantially pure tetrasaccharide of formula (1) described in the application. Methods for preserving an organ.

Abstract: Use of xenon is described. Xenon is used as an organ and/or tissue and/or cell protectant in the manufacture of a pharmaceutical for the protection from injury of organs and/or tissue and/or cells that express HIF.

Abstract: The invention is directed to a method of tissue replacement and repair using a cultured bioremodelable connective tissue construct. The invention is specifically directed to a method for repairing annulus fibrosis of the intervertebral disc, after discectomy surgery where the annulus fibrosis has been opened, with a cultured bioremodelable connective tissue construct.

Abstract: The invention relates to immunotherapeutic compositions and methods for the treatment and prevention of GVHD, humoral rejection, and post-transplantation lymphoproliferative disorder in human subjects using therapeutic antibodies that bind to the human CD19 antigen and that preferably mediate human ADCC. The present invention relates to pharmaceutical compositions comprising human or humanized anti-CD19 antibodies of the IgG1 or IgG3 human isotype. The present invention relates to pharmaceutical compositions comprising human or humanized anti-CD19 antibodies of the IgG2 or IgG4 human isotype that preferably mediate human ADCC. The present invention also relates to pharmaceutical compositions comprising chimerized anti-CD19 antibodies of the IgG1, IgG2, IgG3, or IgG4 isotype that mediate human ADCC. In preferred embodiments, the present invention relates to pharmaceutical compositions comprising monoclonal human, humanized, or chimeric anti-CD19 antibodies.

Abstract: The present invention relates to the discovery that acetylsalicylic acid (ASA or aspirin), salicylic acid (SA) and related salicylate esters and their pharmaceutically acceptable salts, when coadministered in effective amounts with a drug or other bioactive agent which typically (in the absence of the salicylate compound) produces significant hepatotoxicity as a secondary indication, will substantially reduce or even eliminate such hepatotoxicity. Favorable therapeutic intervention results from the use of the present invention having the effect of reducing hepatotoxicity associated with the administration of certain drugs and other bioactive agents and in certain instances of allowing the administration of higher doses of a compound which, without the coadministration, would produce hepatotoxicity which limits or even negates the therapeutic value of the compound.

Abstract: The present invention provides a liver preservation solution containing trehalose and dibutyryl-cAMP. The content of nitroglycerin in the preservation solution is preferably lower than 0.44 mM. In the liver preservation solution of the present invention, since the toxicity due to nitroglycerin, which is observed during liver preservation, has been improved, liver transplantation can be performed with a high engrafted rate.

Abstract: A composition comprising a mixture, having a maximum molar ratio of acid to base of 0.6 and providing water repellency when applied to a substrate surface without etching of said surface, of A) an anionic aqueous fluoroalkyl phosphate solution which provides at least about 75% of the total fluorine content of said composition, and B) a cationic copolymer of fluoroalkyl(meth)acrylate or perfluoroalkylether(meth)acrylate present at a minimum of 0.3 g per 100 g of said composition.

Abstract: The present invention provides methods of screening genes associated with cell regeneration, growth and differentiation and regulators for cell regeneration, growth or differentiation; regulators for cell regeneration, growth or differentiation; and so on.

Abstract: It is intended to provide a method for delivering a drug such as a gene to a tissue or organ for transplant such as skin by use of a laser-induced stress wave (LISW) and thereby producing a high-performance tissue or organ for transplant with a high survival ability and to provide an apparatus for carrying out the method as well as a high-performance tissue or organ for transplant produced by the method. The present invention provides a method for delivering a drug to a graft of a tissue or organ for transplant, comprising applying a drug to a graft of a tissue or organ for transplant and applying, to the graft, a stress wave induced by the laser light irradiation of a light absorber provided in proximity to the graft, wherein the light absorber is made of a substance capable of absorbing a laser light and generating a stress wave.

Abstract: The present invention relates to tissue preservation for autologous and heterologous transplantation. In particular the present invention provides compositions and methods for the long-term storage of surgical conduits ex vivo for subsequent use in coronary artery bypass grafting.

Abstract: Flush preservation solution for the preservation of cells in the absence of a blood supply comprising: v) water for injection; and vi) at least one saccharide such as a monosaccharide, disaccharide, trisaccharide, or polysaccharide and vii) at least one component with pH buffer properties; and viii) at least one component with calcium transport blocking properties or an anti-calcium action activity; method for the preparation thereof; use thereof in transplantation including organs from heart beating or non heart beating donors, in surgery including any situation of warm or cold ischaemia, cardioplegia or open heart surgery, whole limb or whole body preservation in experimentation on living tissues or in culturing and preserving engineered cells, tissues and organs, limbs or the whole body; method for flushing, preserving or flush preservation of cells; and a kit of parts comprising the solution components.

Abstract: Use of a composition which contains at least one semifluorinated alkane compound and at least one liquid siloxane, wherein the composition is of a density in a range of 0.8 to 1.5 g/cm3, for preserving organs or limbs.

Abstract: This application discloses methods and materials for preparing functional microvascular beds in the laboratory. These prevascularized constructs can be used to vascularize engineered tissue constructs or to revascularize damaged or diseased tissues or organs following implantation. The prevascularized constructs may also deliver genetically engineered gene products to the bloodstream.

Abstract: This invention relates to novel ?-galactosidases for the enzymatic removal of the immunodominant monosaccharides on blood products and tissues. Specifically this invention provides a novel family of ?3 glycosidases, used for the enzymatic removal of type B antigens from blood group B and AB reactive blood products, and the GaIiIi antigen from non-human animal tissues, thereby converting these to non-immunogenic cells and tissues suitable for transplantation.

Abstract: It is intended to provide a promoter for inducing expression selectively and strongly in an immunocompetent cell and/or a blood cell such as a lymphocyte. In the invention, the object was achieved by finding that HHV6 MIE promoter, HHV7 MIE promoter and HHV7 U95 promoter unexpectedly induce a specific expression in an immunocompetent cell and/or a blood cell such as a T lymphocyte. By utilizing the promoters, a selective delivery of a DNA vaccine or the like can be realized.

Abstract: The present invention describes devices, solutions, and methods for the ex-vivo assessment, resuscitation, triage, and maintenance of human candidate cadaveric hearts.

Abstract: The present inventors discovered for the first time that labeling cell nuclei makes it possible to efficiently isolate stem cells. Namely, it was elucidated that stem cells with labeled nuclei remained labeled even after cell division, and showed self-renewing and long-living abilities characteristic of stem cells. Efficient isolation of stem cells is possible, for instance, by labeling the nuclear of each cell in a heterogeneous cellular group followed by selecting those cells that maintain a labeled state even after cell division. The present invention provides methods for enabling visualization of stem cells of animal tissues in a living state by labeling using the essential functions of the stem cells, and methods for simply and easily isolating the stem cells in a fresh state without using at all genetic manipulation or artificial markers.

Abstract: The invention provides for methods and materials to decellularize a solid organ and to recellularize such a decellularized organ to thereby generate a solid organ.

Abstract: A tissue, such as an amniotic or chorionic membrane, harvesting device that integrates a system facilitating subsequent storage of tissue samples. The device cuts a sample of the target tissue and automatically deposits the sample in a storage vessel. A method of collecting and storing a sample from a target tissue using a tissue harvesting device. A kit for collecting and storing samples of the target tissue.

Abstract: The invention is directed to methods and devices for the reconstruction, repair, augmentation or replacement of laminarily organized organs or tissue structures in a patient in need of such treatment. The device comprises a biocompatible synthetic or natural polymeric matrix shaped to conform to at least a part of the luminal organ or tissue structure with a first cell population on or in a first area and a second cell population such as a smooth muscle cell population in a second area of the polymeric matrix. The method involves grafting the device to an area in a patient in need of treatment. The polymeric matrix comprise a biocompatible and biodegradable material.

Abstract: The invention provides compounds of formula (I), wherein R, R1, R2, R3 and R4 are as defined in the description, and their preparation. The compounds of formula I are useful as biomarkers.

Abstract: The present invention is concerned with proteins selected from the members of the TGF-? superfamily, which are monomeric due to substitution or deletion of a cysteine which is responsible for dimer formation. The invention is also concerned with nucleic acids, encoding such monomeric proteins, vectors or host cells containing the nucleic acids as well as with pharmaceutical compositions comprising the proteins or nucleic acids encoding the proteins. The compositions can be applied advantageously for all indications for which the respective dimeric proteins are useful.

Abstract: Instead of immersing human reproductive cells in a single culture medium throughout the various procedures used in IVF, a process is provided by which the reproductive cells may be moved through a sequence of distinct culture media as the various IVF procedures are carried out. In one implementation, the culture media specifically formulated to provide a physical environment similar to that found within the female reproductive tract and conducive to growth and development of human reproductive cells during the various stages of the IVF process. In this regard, specifically formulated culture media can be applied to support the reproductive cells in one or more of the following procedures: oocyte retrieval and handling; oocyte maturation; ordinary fertilization; oocyte, zygote and embryo examination and biopsy; embryonic development to the eight-cell stage; embryonic development to the blastocyst stage; embryo transfer, and cryopreservation.

Abstract: A process for preserving tissues is described which comprises transferring the tissues in a container and evacuating the container.

Abstract: A method for the preparation of antimicrobially active materials is presented. The invention involves taking a base material such as allografts, xenografts, polymers, metals, and ceramics and combining it with an antimicrobially active agent, such as antibiotics, antibacterials, antifungals, antivirals, disinfectants, and polypeptides, after which it is irradiated with ionizing radiation to sterilize and stabilize the combined material. The resulting antimicrobially active material may then be stored at ambient temperature while maintaining its antimicrobial activity and the structural integrity of the base material. The invention is particularly useful for both preventing and treating a variety of infections and for increased safety in reconstructive procedures.

Abstract: Methods are disclosed for determining whether organ toxicity, particularly cardiotoxicity, will occur in a patient selected for treatment with various kinase inhibitors, such as tyrosine kinase inhibitors, more particularly erbB inhibitors such as Herceptin. In addition, methods are disclosed for determining whether a potential drug is likely to produce a cardiotoxic effect. The methods involve analyzing lipid levels or the expression fatty acid oxidation enzymes, pAMP activated protein kinase, glucose uptake, to determine whether a fatty acid oxidation disorder is present. The identification of a fatty acid oxidation disorder can be used as a predictor of toxicity, especially cardiac toxicity, and as an indication that organ function should be carefully monitored if a drug such as a tyrosine kinase inhibitor is administered. Methods are also disclosed for protecting organs from metabolic stress and for the treatment of cells, such as adipocytes, to reduce their lipid content.

Abstract: This invention is a novel method for perfusion of a porous implant which achieves efficient interpenetration of desired factors into and removal of undesirable factors from the pores of the implant, cleaning of the implant, efficient passivation of the implant (inactivation of pathogens, microorganisms, cells, viruses and the like and reduction in antigenicity thereof), and the novel implant produced by such treatment. The process presents a system wherein the rate of pressure cycling, the fact of pressure cycling, and the amplitude of pressure cycling, results in highly cleaned tissues and other implants for implantation.

Abstract: Stretch-induced increased hemodynamic load adversely affects endothelial cell function and is an important contributor to thromboembolus formation in heart failure, valvular heart disease, atrial fibrillation, venous insufficiency, and pulmonary hypertension, and in thrombus occluded vein grafts. Local thrombus formation and thromboenbolic events can be reduced by inhibiting the TGF-beta signaling pathway or TGF-beta per se. Inhibitors can be administered to patients or veins (prior to interposition) at risk for thromboembolic events or local thrombus formation. Inhibitors can be applied to harvested veins to be used as arterial grafts.

Abstract: The present invention provides ungulates, including pigs, expressing CTLA4-Ig, as well as tissue, organs, cells and cell lines derived from such animals. Such animals, tissues, organs and cells can be used in research and medical therapy, including xenotransplanation. In addition, methods are provided to prepare organs, tissues and cells expressing the CTLA4-Ig for use in xenotransplantation, and nucleic acid constructs and vectors useful therein.

Abstract: The invention discloses a family of peptides termed NRP compounds or NRPs that can promote neuronal migration, neurite outgrowth, neuronal proliferation, neural differentiation and/or neuronal survival, and provides compositions and methods for the use of NRPs in the treatment of brain injury and neurodegenerative disease. NRP compounds can induce neurons and neuroblasts to proliferate and migrate into areas of damage caused by acute brain injury or chronic neurodegenerative disease, such as exposure to toxins, stroke, trauma, nervous system infections, demyelinating diseases, dementias, and metabolic disorders. NRP compounds may be administered directly to a subject or to a subject's cells by a variety of means including orally, intraperitoneally, intravascularly, and directly into the nervous system of a patient. NRP compounds can be formulated into pharmaceutically acceptable dose forms for therapeutic use.

Abstract: A tissue transfer method for reconstruction and augmentation of soft tissue. The method includes harvesting adipose tissue from a patient. The harvested tissue is processed via centrifugation to isolate a purified subset of the adipose tissue including separating and removing a substantial amount of triglycerides from the harvested adipose tissue. The centrifugation may be performed to cause separation of water from the purified adipose tissue and to cause separation of oil from mature adipocytes. Specifically, the spin rates may be selected to be high enough to cause lesions in the mature adipocytes that results in the release of the oil. The method continues with implanting the purified adipose tissue into the patient at a breast or other area identified for reconstruction or augmentation. The implanting is performed based on an injection pathway model that defines injection point locations and a number of injection pathway directions from each point.

Abstract: The present invention relates to the qualitative and quantitative validation of marker indices, especially for medical diagnosis and particularly for the determination of the growth fraction in a sample with antibodies against the Ki-67 protein. Diagnostic kit for the quantification of a cell fraction labeled by a marker for in vitro diagnosis, characterized in that a pseudo-tissue is used for the intra- and inter-assay standardization of the marker index.

Abstract: The present invention is directed to methods of treating or preventing atherosclerosis and other cardiovascular diseases by administering agents that inhibit or modulate the NOTCH signaling pathway. In addition, the invention encompasses methods for assaying compounds for their ability to treat atherosclerosis based upon their effects on NOTCH signaling, and for measuring levels of amount, function, or activity of NOTCH pathway components in biological samples.

Abstract: Disclosed is the use of prelamin A pre peptide and homologues or analogs thereof for the induction of cell differentiation and tissue or organ growth and repair processes. The invention extends to virtually any cell, including both embryonic and non-embryonic stem cells, such as stem cells that are progenitors for a wide variety of cell and tissue types. Also disclosed is the use of prelamin A pre peptide and prelamin A to determine and establish cell morphology and tissue architecture. Treatment of a variety of diseases and conditions, as well as cosmetic, general health, and anti-aging applications are described.

Abstract: This document relates to methods and materials involved in detecting tissue injury and/or rejection (e.g., injury and/or rejection of transplanted tissue). For example, this document relates to methods and materials involved in the early detection of kidney tissue injury.

Abstract: The present invention relates to tissues and tissue sheets assembled from adipose-derived stromal cells. Particularly, it relates to reconstructed adipose tissues which comprise adipocytes as well as reconstructed conjunctive tissues which comprise adipose-derived stromal cells. The reconstructed tissues and sheets can be used, for example, in cosmetic applications for the replacement or addition of soft tissues, in pharmacological and toxicological applications for the in vitro testing of small molecules or cosmetic products as well as in therapeutic applications for the delivery of agents.

Abstract: Methods of inhibiting annexin I induced apoptosis by contacting a cell population containing a TRPM7/ChaK1 kinase with an effective amount of a composition containing an inhibitor for the kinase.

Abstract: A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification. The method includes applying a calcification mitigant such as a capping agent or an antioxidant to the tissue to specifically inhibit oxidation in tissue. Also, the method can be used to inhibit oxidation in dehydrated tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the oxidation and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. In one method, tissue leaflets in assembled bioprosthetic heart valves are pretreated with an aldehyde capping agent prior to dehydration and sterilization.

Abstract: Methods for defatting omentum and processes for preparing an a cellular omentum i.e., devitalized or decellularized omentum, comprising extracellular matrix for implantation into a mammalian system. Also constructs for medical applications comprising decellularized omentum.

Abstract: Polyglycerol, lactose, and a combination of polyglycerol and lactose are effective at preserving cells, tissues, and organs from damage due to hypothermic, ischemic, or other metabolic impairment, and a mixture of polyglycerol plus lactose is particularly useful for the hypothermic storage of cells, tissues, and organs. The mixture of polyglycerol and lactose can be further improved by the addition of chondroitin sulfate, chlorpromazine, calcium, citrate, glutathione, adenine, glucose, magnesium, and a pH buffer.

Abstract: A method of injecting cells into a biological tissue comprising thrusting injection needle (200) under microvibration into tissue (5) secured by suction to tissue suction means (210) and effecting injection of a cell suspension into the tissue through the needle. There is also provided an apparatus for cell injection into the biological tissue.

Abstract: The invention relates to the genetic manipulation of non-human animals. More particularly, the invention relates to genetic manipulation of non-human animals to be used for xenotransplantation. The invention provides viable gene knockout swine including swine in which the ?(1,3)-galactosyltransferase gene has been disrupted, methods for making such swine, and methods of using the tissues and organs of such swine for xenotransplantation.

Abstract: The present invention provides a reversibly immortalized mammalian liver cell line, especially CYNK-1 (deposited with International Patent Organism Depository, National Institute of Advanced Industrial Science and Technology, address: AIST Tsukuba Central 6, 1-1, Higashi 1-Chome, Tsukuba-shi, Ibaraki-ken, 305-8566 Japan, deposited date: Mar. 10, 2004, accession number: FERM BP-08657) comprising an immortalizing gene interposed between a pair of site-specific recombination sequences and a suicide gene in the outside of the pair of site-specific recombination sequences, characterized in that the suicide gene can exhibit its function after excision of the pair of site-specific recombination sequences, or passage cell line thereof; a mammalian liver cell obtained by excising the immortalizing gene from the reversibly immortalized mammalian liver cell line or passage cell line thereof; and use of these cells.

Abstract: A three-dimensional reconstruct model containing solid layers of collagen and fibroblasts closely mimic the condition of patients in vivo, preserving in vivo phenotypic and functional characteristics of the cells. Reconstructs can be used to detect cellular migration, including active migration of cytotoxic T lymphocytes towards tumor cells, which can be measured by detecting tumor cell lysis. Reconstructs also can be used to identify factors that influence migration of cells, including chemokines that influence migration of cytotoxic T lymphocytes, as well as to identify tumor antigens.

Abstract: The present invention relates to a method for producing cancerous disease modifying antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies for therapeutic and diagnostic purposes. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat primary tumors and tumor metastases. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells.

Abstract: A carrier for cell culture is provided which improves the cell proliferativity in serum-free culture and which is free from risk from infection factor contamination. The gist of the features of the present invention is to be formed of a crosslinked poly (meth) acrylic acid (salt) particle (A) and an artificial polypeptide (P) having at least one cell-adhesive minimal amino acid sequence (X) in one molecule and to have a water retention value of from 2 to 50 g/g. The (A) is preferably a particle produced by reversed phase suspension polymerization of an aqueous monomer solution containing (meth)acrylic acid and/or an alkali metal salt of (meth)acrylic acid. The (P) preferably has at least one auxiliary amino acid sequence (Y) in one molecule of the (P). The (X) is preferably an Arg Gly Asp sequence.

Abstract: Methods of treating disorders related to CXCL13 activity utilize CXCL13 antagonists and, optionally, TNF? antagonists, such as antibodies, including specified portions or variants, polypeptides, polynucleotides, siRNA, shRNA, ribozymes, and DNAzymes. Disorders related to CXCL13 activity include inflammatory disorders, such as pulmonary disorders, for example, asthma, emphysema, and COPD, and systemic lupus erythematosus.