Abstract: The invention provides a composition comprising SGEF protein or gene as a therapeutic means to clinical or subclinical defects associated with anomalies of at least one from among the macula, corpus callosum, hippocampus, liver or immune system and diseases including a feverless response to infection, a cancer or vision loss. Methods of diagnosis of such disease and development anomalies are based on detection of mutations of the SGEF gene or altered levels of the SGEF mRNA or protein. A change of at least about 20% in the level of expression visa-vie a normal individual indicates an SGEF anomaly. The SGEF protein is also used as a preventive or curative treatment of atherosclerosis by local or systemic delivery. The invention also provides a composition comprising an inhibitor of the SGEF gene expression or SGEF protein concentration, as a therapeutic means for glaucoma, osteoarthritis, auto-inflammatory diseases, tumors or cancers.

Abstract: Methods are provided for producing novel multicellular compositions comprising cancer cells together with pluripotent human stem cells, which are capable of proliferating and differentiating into various normal cell lines and tissue structures. These novel multicellular compositions are useful for investigating the properties of cancer cells in a normal human tissue microenvironment, and for studying interventions that will modulate these properties including devising, testing and screening therapeutic drugs.

Abstract: Methods of validating results of assessments of test substances using human-derived tissues and/or organs, particularly tissues and/or organs unsuitable for transplantation, include assessing the suitability of the organ and/or tissue for substance testing, as well as inter-organ variability and use of exogenous and/or endogenous controls.

Abstract: The invention relates generally to methods and compositions for the cryopreservation and/or vitrification of tissue including articular cartilage and the preparation of said tissue for clinical or research use, including but not limited to joint replacement and the treatment and prevention of osteoarthritis.

Abstract: Biological tissues may be prepared for use in biological prostheses. The biological tissue may be fixated with glutaraldehyde and may be subjected to successive treatment of the tissue with a solution containing taurine to neutralize excess aldehyde groups that remain free after fixation.

Abstract: An organ protectant solution which is intravenously administerable includes a high concentration of cell impermeant molecules which have a charge and/or molecular weight which permit passage across a capillary endothelium and into an interstitial space in said subject but which are too large and/or charged to cross a cell plasma membrane such that said one or more cell impermeant molecules preferentially load into an extracellular fluid compartment can be used to to allow for improved organ harvesting from DCD and brain death donors for transplantation purposes and also can be used extend the “Golden Hour” for traumatic and hemorrhagic shock patients thereby allowing more time for those patients to reach a point of care facility to receive medical treatment.

Abstract: The present invention relates, e.g., to a method for predicting the embryonic progression of a preimplantation embryo, comprising measuring in the insemination medium (IM) in which an oocyte was fertilized and subsequently incubated in vitro, thereby generating a pre-implantation embryo, at 18-24 hrs post fertilization, the levels of nitric oxide metabolites (NOx) in the insemination medium (IM), wherein a level of NOx of at least about 1.3 ?M indicates that the preimplantation embryo is likely to progress to the blastocyst stage by culture day (CD) 5.

Abstract: It is provided an improved aqueous solution for the preservation of tissues and organs comprising carvedilol, tacrolimus, and trimetazidine. A synergistic effect is observed for this preservation solution which is particularly effective in marginal organs, such as steatotic livers.

Abstract: The invention relates to a method for preserving an organ or tissue comprising contacting the organ or tissue with an effective amount of a kallikrein inhibitor and solutions useful for such a method. Also provided is a method for reducing reperfusion injury of an organ during surgery and/or following removal of the organ from a subject comprising placing the organ in an organ storage and preservative solution, wherein the solution comprises a kallikrein inhibitor.

Abstract: The present invention relates to a heart valve and, more particularly, to a mold and process shaping and securing cells and tissue layers as they are grown in three-dimensions into a heart valve.

Abstract: A normal regenerated tissue is formed by exposing to radiation a connective tissue or a supporting tissue originating in an organ to thereby form a feeder layer and then transplanting epithelial cells thereon to form a stratified structure. By conveniently and surely providing regenerated tissue by the 3-dimensional culture with the use of a human-origin normal tissue as a base, it is possible to construct systems for assessing effects and side effects of chemicals such as drugs or assessing sensitivities thereof with the use of regenerated tissues as models of corresponding tissues respectively.

Abstract: Embodiments include methods for decellularizing an organ or tissue comprising conditioning the organ or tissue to be decellularized by exposing the organ or tissue to an electric current, as well as methods of using such decellularized organs or tissues.

Abstract: A method for making a tissue includes seeding cells at a selected concentration on a support to form a cell spot, incubating the cells to allow the cells to partially attach, rinsing the cells to remove any unattached cells, adding culture medium to enable the cells to proliferate at a periphery of the cell spot and to differentiate toward a center of the cell spot, and further incubating the cells to form the tissue. The cells may be C2C12 cells or other subclones of the C2 cell line, H9c2(2-1) cells, L6 cells, L8 cells, QM7 cells, Sol8 cells, G-7 cells, G-8 cells, other myoblast cells, cells from other tissues, or stem cells. The selected concentration is in a range from about 1×105 cells/ml to about 1×106 cells/ml. The tissue formed may be a skeletal muscle tissue, a cardiac muscle tissue, nerve tissue, or a bone tissue.

Abstract: The present disclosure provides a variety of methods and compositions (e.g., solutions) useful for making, sterilizing, and preserving tissues (e.g., acellular tissue matrices). The disclosure also features the acellular tissue matrices made by the methods, which matrices can be used for a variety of applications such as, but not limited to, treating an injury to, or repairing, a large number of tissues and/or organs (e.g., e.g., fascia, bones, and/or cartilage) in a mammal (e.g., a human).

Abstract: A spermatogonial stem cell line that is derived from testes of rats characterized by a desirable genetic background can serve as a source for cells to transplant into male-sterile recipient animals that are immuno-compatible with the spermatogonial line. Rat cells thus transplanted readily develop into fertilization-competent, haploid male gametes, with little or no endogenous sperm competition generated by the testes of the male-sterile recipient. This approach, constituting the first vector system for the use of rat spermatogonial lines from in vitro culture in generating mutant rats on a desired genetic background, effects maximal germline transmission of donor haplotypes from the transplanted spermatogonial cells.

Abstract: Methods for treating a bioprosthetic tissue are described. The methods comprise contacting the biological tissue with an anchor compound, the anchor compound comprising first and second functional groups. The first functional group is reactive with and couples a tissue functional group associated with the biological tissue. The second functional group is one of a bio-orthogonal binding pair. The biological tissue coupled to the anchor compound is then exposed to a linking compound. The linking compound comprises at least two functional groups, each comprising the other one of the bio-orthogonal binding pair. In a preferred embodiment, the bio-orthogonal binding pair is an azide and an acetylene. The method can be performed in the presence of a catalyst, preferably a copper catalyst. Alternatively, the method can be performed in the absence of a catalyst, wherein the acetylene is incorporated in a ring-strained cyclic compound, such as cyclooctyne.

Abstract: The present invention comprises a specimen preserver. A bubble reservoir is used to hold a preserving liquid such as artificial cerebrospinal liquid (aCSF). Oxygen is introduced into the aCSF by a gas diffuser which is attached to the bubble reservoir. The tissue samples are contained in one or more chambers in a holding platform. The platform is suspended well above the bottom of the bubble reservoir. The lower portion of each of the chambers is open toward the bottom of the bubble reservoir, but is covered by a fine mesh. The gas introduced into the aCSF circulates within the bubble reservoir. However, the tissue samples are not directly exposed to the gas bubbles because the fine mesh excludes the bubbles from the chambers in which the tissue samples are housed.

Abstract: The present invention concerns a method of treating an advanced lung disease in a patient in need thereof by lung transplantation.

Abstract: A avian cell line that supports replication of animal or human viruses, which cell line is adapted to animal-product free growth. The cell line is useful for propagating a virus suitable as a live or a killed vaccine and for virus isolation and diagnostic assays.

Abstract: This disclosure provides solutions, systems, and methods for cell, tissue, and/or organ preservation. Some preservation solutions may include any combination of a balanced salt solution, electrolytes, antibiotic agents, antimycotic agents, protease inhibitors, anti-oxidants, simple sugars, starches impermeant ions, uric acid and/or amino acids. Some preservation solutions may also include hydrolyzed collagen. The preservation solutions including hydrolyzed collagen may be used alone or as part of a kit to preserve cells, tissue, or organs. The solution may also be used in connection with one or more medical procedures, for example organ transplantation.

Abstract: The invention relates to solutions carrying high levels of oxygen, e.g. to aqueous solutions having an oxygen concentration of at least 30 mg/L, especially at least 70 mg/L, and to uses thereof. The aqueous solutions contain colloidal minerals which help stabilise the high oxygen levels. The super-oxygenated fluids may be used to affect the viability, growth and maintenance of cells, tissues and organs.

Abstract: The invention provides double knockout transgenic pigs (GT/CMAH-KO pigs) lacking expression of any functional ?GAL and CMAH. Double knockout GT/CMAH-KO transgenic organs, tissues and cells are also provided. Methods of making and using the GT/CMAH-KO pigs and tissue are also provided.

Abstract: Described herein are enhanced compositions and methods for storing biomaterials. In certain aspects, these biomaterials include natural and engineered eukaryotic tissues. The methods described herein include storing these biomaterials in such a manner that reduces or prevents the loss of biomaterial properties (e.g., extracellular matrix integrity, cell viability, or a combination thereof) occurring either during storage or after removal of the biomaterial from storage. In certain aspects, these biomaterials will be stored in animal product-free solutions containing an agent that prevents or reduces the loss of extracellular matrix integrity.

Abstract: The invention relates to the use of a composition comprising at least one globin, one globin protomer or one extracellular hemoglobin of Annelida, a stabilizing solution and/or a solution for conserving organs, said composition having a temperature of between 0° C. and 37° C., for preserving an organ in a donation after brain death donor or a donation after cardiac death donor. The invention also relates to a method for conserving an organ in situ in a donation after brain death donor or a donation after cardiac death donor using normothermic ECMO or double-balloon triple-lumen catheter techniques or any other similar technique.

Abstract: Disclosed is a tissue-derived biomaterial carrier device (1) comprising a carrier case 810), an arm (125) provided upright on an interior bottom wall surface of the carrier case (10), a mounting part (121), a swing mechanism (122), a temperature control box (20) provided detachably on an exterior wall surface of the carrier case (10), and a heater (201) provided in the temperature control box (20). The mounting part (121) receives the mounting of a housing vessel in which a tissue-derived biomaterial is housed (an opening part (121a)). The swing mechanism (122) swingably supports the mounting part (121) relative to the arm (125). With the temperature control box (20) mounted on the carrier case (10), the heater (201) in the temperature control box (20) receives the supply of electric power from a battery (203) and regulates the temperature within the carrier case (10).

Abstract: A method of sustaining cells is provided. The method can include providing a non-perfluorocarbon cell storage medium, providing a pre-oxygenated liquid perfluorocarbon in contact with the storage medium, and placing the cells in contact with the storage medium but not in contact with the perfluorocarbon. Additionally, the method can result in increased corneal cell viability compared to corneal cells placed in a non-perfluorocarbon cell storage medium without being in contact with a pre-oxygenated liquid perfluorocarbon.

Abstract: The present invention provides methods of reducing the cytotoxic effects of nitric oxide and sulfides comprising coadministering nitric oxide with sulfide. In addition, the present invention provides novel pharmaceutical compositions comprising both nitric oxide and sulfide. The methods and compositions of the present invention may be used in the treatment or prevention of a variety of diseases and disorders, and also in the prevention of cell or tissue damage, including that resulting from ischemia or hypoxia.

Abstract: For cooling organs and tissues in transplantation medicine, only ice preparations are used so far which are not soft like a gel and are brought to the necessary degree of comminution by mechanically comminuting frozen, sterile, pyrogen-free isotonic infusion solutions, such as 5% glucose or 0.9% saline, with great effort. The lack of gel-like consistency of the preparations and the expensive production process are very disadvantageous. Therefore, it was necessary to produce a cooling preparation for transplantation medicine, which in a temperature range from ?5° C. to 4° C. is gel-like and soft, transparent and sufficiently mechanically stable and yet remains formable. In accordance with the invention, such preparation can be produced from gelatin solutions in the concentration range of 3-20 wt-%, which are isotonized or adjusted to 280-650 mosmol/kg and are almost pH-neutral, by simple cooling and/or freezing.

Abstract: Disclosed herein are compositions and methods useful for preparing neural scaffolds. The scaffolds comprise tissue taken from the spinal cord and/or dura mater of vertebrate and can be processed to form gels or sheets. Methods of treating patient with CNS injury are also presented.

Abstract: In one embodiment, a preservation apparatus is described that includes a storage compartment. The storage compartment is configured to hold an organ or tissue and a preservation fluid. A cover assembly is configured to engage the storage compartment. The cover assembly includes a support element, wherein the support element together with the storage compartment define a storage chamber. The cover assembly also includes a lid and a gas permeable membrane disposed between the lid and the support element. The gas permeable membrane and the support element together define a perfusion chamber configured to hold preservation fluid and an organ or tissue during use.

Abstract: Embodiments of the present invention provide Dermal Micro-organs (DMOs), methods and apparatuses for producing the same. Some embodiments of the invention provide a DMO including a plurality of dermal components, which substantially retain the micro-architecture and three dimensional structure of the dermal tissue from which they are derived, having dimensions selected so as to allow passive diffusion of adequate nutrients and gases to cells of the DMO and diffusion of cellular waste out of the cells so as to minimize cellular toxicity and concomitant death due to insufficient nutrition and accumulation of waste in the DMO. Some embodiments of the invention provide methods and apparatuses for harvesting the DMO. An apparatus for harvesting the DMO may include, according to some exemplary embodiments, a support configuration to support a skin-related tissue structure from which the DMO is to be harvested, and a cutting tool able to separate the DMO from the skin-related tissue structure.

Abstract: Methods and compositions are provided for the cryopreservation of human organs and tissues. In certain embodiments, Step 1 comprises perfusion with a vitrifiable cryoprotectant solution at a temperature above ?10° C. for a time insufficient for the approximate osmotic equilibration of the organ with the solution, followed by cooling the organ to below ?10° C. by perfusion with said solution at a reduced temperature. In certain embodiments, Step 2 comprises increasing the concentration of cryoprotectant further at a temperature from ?10 to ?40° C. In certain embodiments, Step 3 comprises cooling and vitrifying the organ, rewarming it, and perfusing the organ with a vitrifiable concentration of cryoprotectant whose temperature is either raised gradually or is held at ??15° C. Compositions are provided that allow safe organ perfusion with vitrifiable media at >?10° C. and almost complete avoidance of chilling injury at ?20 to ?25° C. and that allow slow warming after vitrification without freezing.

Abstract: Methods and materials for treating various diseases and medical conditions with meso-biliverdin compositions. In addition methods and materials for producing meso-biliverdin are provided where the methods include reacting phycocyanobilin with an amphoteric compound in a solvent to yield meso-biliverdin are provided.

Abstract: Extracellular organ or tissue rinsing solution, comprising calcium, PEG with a molecular weight of 35 000 at a concentration of at least 4 g/l, and potassium at a concentration of greater than or equal to 1, but less than 10 mmol/l.

Abstract: The present invention relates to CD82 polypeptides of the mammalian tetraspanin CD82 protein family for use in the diagnosis, prevention and/or treatment of xenograft recognition and/or rejection. The present invention furthermore relates to CD82 knockout and transgenic animals and their cells, tissues and organs. The present invention furthermore relates to antibodies against a CD82 polypeptide, pharmaceutical compositions comprising at least one inhibitor of a CD82 polypeptide or comprising cells, tissues and organs of animals in which the CD82 level, expression and/or activity is modified, and their use in the diagnosis, prevention and/or treatment of xenograft recognition and/or rejection. The present invention furthermore relates to methods of diagnosing xenograft recognition and/or rejection and methods for the prevention and/or treatment of xenograft recognition and/or rejection as well as methods of xenotransplantation.

Abstract: The development and construction of implantable artificial organs, and a process for manufacturing three-dimensional polymer microscale and nanoscale structures for use as scaffolds in the growth of biological structures such as hollow organs, luminal structures, or other structures within the body are disclosed.

Abstract: Apparatus for processing life-based organic particles, including particles selected from the list comprising cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos, comprises a hollow volume (10) that (a) is internally divided into at least first (14), second (16) and third (17) sub-volumes by at least two phaseguides (12, 13) formed inside the volume and (b) includes parts that are relatively upstream and relatively downstream when judged with reference to the movement of a meniscus or a bulk liquid in the volume (10). The apparatus includes at least first, second and third fluid conduits (19, 21, 22) connected to permit fluid communication between the upstream exterior of the volume (10) and a respective said sub-volume (14, 16, 17); and at least one further conduit (24) connected to permit fluid communication between the downstream exterior of the volume (10) and a said sub-volume.

Abstract: The subject application provides for an emulsion comprising an amount of a perfluorocarbon liquid dispersed as particles within a continuous liquid phase, wherein the dispersed particles have a monomodal particle size distribution and uses thereof. The subject application also provides for a method of manufacturing a perfluorocarbon emulsion, a process for preparing a pharmaceutical product containing a PFC emulsion and a process for validating a batch of an emulsion for pharmaceutical use.

Abstract: Methods for modification of tissue using covalent chemistry. Tissue can be modified through direct alkylation, reduction followed by alkylation, or oxidation followed by condensation to covalently attach small organic molecules or appropriately modified proteins. The modification can be spatially limited to desired regions of the tissue surface.

Abstract: This invention relates generally to a dehydration device and methods for drying biological materials to produce dried biological materials having enhanced structural properties. More specifically, the invention relates to a dehydration device and related methods for drying biological tissue to produce enhanced tissue grafts.

Abstract: The present invention relates to compounds that act as agonists of the Wnt signalling pathway, compositions comprising these compounds and the uses of these compounds, both therapeutic and in research. The invention also provides methods of identifying compounds that act as agonists of the Wnt signalling pathway.

Abstract: Methods and materials for making complex, living, vascularized tissues for organ and tissue replacement, especially complex and/or thick structures, such as liver tissue is provided. Tissue lamina is made in a system comprising an apparatus having (a) a first mold or polymer scaffold, a semi-permeable membrane, and a second mold or polymer scaffold, wherein the semi-permeable membrane is disposed between the first and second molds or polymer scaffolds, wherein the first and second molds or polymer scaffolds have means defining microchannels positioned toward the semi-permeable membrane, wherein the first and second molds or polymer scaffolds are fastened together; and (b) animal cells. Methods for producing complex, three-dimensional tissues or organs from tissue lamina are also provided.

Abstract: The present invention generally relates to methods and compositions to determine viability of an organ for transplantation and other medical purposes. One aspect of the invention relates to a method for assessing the viability of an organ by measuring the energy parameters to determine the energy level of the organ by determining the stored cellular energy (e.g., ATP levels), and/or energy consumption over a particular time period of viability. The energy parameters can be compared to reference energy parameters as a highly accurate and reliable prediction of viable cell yield, and organ viability. Another aspect of the invention relates methods to preserve or extend the time period of viability of an organ any combination of (i) preservation perfusion of the organ to prevent ischemic damage, (ii) chemical metabolic suppression of the organ e.g., using metabolic suppressants, (iii) metabolic suppression by physical or environmental conditions, e.g., sub-zero non-freezing storage.

Abstract: A liquid plasma expander or resuscitation fluid composition for use in a subject in need thereof, comprising, consisting of, or consisting essentially of: (a) a keratin derivative (preferably alpha keratose, gamma keratose, or combinations thereof, and with basic alpha keratose preferred over acidic alpha keratose); and (b) an electrolyte solution, with the keratin derivative solubilized in the electrolyte solution to form a homogeneous liquid composition. Blood substitutes formed therefrom and methods of making and using the same are also described.

Abstract: The current invention provides a new organ preservation solution, suitable for machine perfusion, for maintaining viability of organs, parts of organs and tissues. This solution has been designed to overcome a number of problems associated with hypothermic machine perfusion of donor organs, in particular organs obtained from non-heart-beating donors. The solution prevents or minimizes the adverse affects caused by ischemia, hypoxia, energy and nutrient depletion, acidification, hypothermia and reperfusion injury. The preservation solutions according to the current invention are superior to current state of the art preservation solutions, in particular for preservation and perfusion of organs obtained from non-heart-bearing donors, by supplying increased concentrations and an optimized balance of amino acids, vitamins, anti-oxidants, high molecular weight additives and enhanced buffering capacity.

Abstract: The present invention relates to a transgenic pig that expresses sTNFR1-Fc, wherein a gene encoding sTNFR1-Fc, which is a fusion protein of the extracellular domain of human soluble tumor necrosis factor receptor (sTNFR1) and an immunoglobulin Fc region, is introduced; a method for preparing the same; an organ isolated from the transgenic pig; a somatic donor cell line inserted with sTNFR1-Fc gene; a method for preparing a blood sample comprising sTNFR1-Fc; and a method for preparing human sTNFR1-Fc from the blood sample of the transgenic pig. As the transgenic pig can suppress immune response and inflammatory response by secreting an inhibitory substance that suppresses the activity of TNF-? in blood, it can be effectively used for xenograft. Furthermore, since the transgenic pig has a blood type O, it can be transplanted for suppressing inflammatory response, regardless of a blood type of recipient.

Abstract: Provided is a novel method capable of producing an artificial skin model. A method for producing an artificial skin model includes: providing coated cells (1), each of which is obtained by covering the surface of a cell (3) with a coating film (2) containing an extracellular matrix component; forming a dermis tissue layer (7), in which the coated cells (1) are laminated, by culturing the coated cells (1); and forming an epidermis layer (12) by arranging epidermis cells (8) on the dermis tissue layer (7).

Abstract: A perfusion apparatus including a perfusion circuit that perfuses an organ or tissue has a compartment that supports an organ or tissue during perfusion, an internal cover, and an external cover that closes the apparatus. A wall portion may extend substantially perpendicularly between the internal cover and the external cover to define a document compartment between the internal cover, the external cover and the wall portion. A tamper evident seal will not permit the external cover to open without creating a record of whether the external cover has been opened after the tamper evident seal has been activated.

Abstract: An apparatus for at least one of storage, treatment, assessment and transport of an organ or tissue includes a coolant container configured to cool the organ or tissue, a perfusion circuit configured to perfuse the organ or tissue, and a sample compartment for holding a biological sample. Preferred apparatus has a first internal compartment under a first cover (lid) of the apparatus that includes the coolant container and the sample compartment. The apparatus can include a second internal compartment under a second cover (lid) of the apparatus, the second internal compartment including at least part of the perfusion circuit and a sample compartment.

Abstract: The present invention provides certain donor animals, tissues and cells that are particularly useful for xenotransplantation therapies. In particular, the invention includes porcine animals, as well as tissue and cells derived from these, which lack any expression of functional alpha 1,3 galactosyltransferase (aGT) and express one or more additional transgenes which make these animals suitable donors for xenotransplantation of vascularized xenografts and derivatives thereof. Methods of treatment and using organs, tissues and cells derived from such animals are also provided.