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.

Abstract: The present invention provides compositions comprising desiccated biologics comprising a cell, protein, virus, nucleic acid, carbohydrate, or lipid, or any combination thereof, along with at least one membrane penetrable sugar, and at least one membrane impenetrable sugar, wherein the moisture content is from 5% to 95%, and to methods of preparing the same, and to methods of treating animals using the same.

Abstract: Compressible and concentrated suspensions containing gas-filled microbubbles, uses thereof for delivering gas into a subject in need thereof, and systems for delivering the compressible suspensions. The gas-filled microbubbles each comprise a gas core surrounded by a lipid membrane, which includes (a) one or more lipids, such as 1,2-disteroyl-sn-glycero-3-phosphocholine (DSPC) or dipalmitoylphosphatidylcholine (DPPC), and (b) one or more stabilizing detergents, such as poloxamer 188, Pluronic F108, Pluronic F127, polyoxyethylene (100) stearyl ether, cholesterol, gelatin, polyvinylpyrrolidone (PVP), and sodium deoxycholate (NaDoc).

Abstract: The present invention relates to a method for reducing electrical disturbance of a cell's resting membrane potential comprising administering an effective amount of a composition comprising an effective amount of a local anaesthetic and of one or more of a potassium channel opener, an adenosine receptor agonist, an anti-adrenergic, a calcium antagonist, an opioid, an NO donor and a sodium hydrogen exchange inhibitor.

Abstract: The present invention relates to a composition for controlling viability of a tissue including a potassium channel opener or adenosine receptor agonist, a compound for inducing local anaesthesia and compound for reducing the uptake of water by a cell in the tissue. The present invention also relates to the use of the composition according to the invention for controlling viability of a tissue.

Abstract: A method of enhancing the formation of extracellular matrix in culture. Cells in culture secrete most of the collagen into the media as unprocessed procollagen, i.e., the cells do not convert procollagen to collagen. In contrast, normal extracellular matrix deposition involves procollagen processing to collagen, fibril assembly and deposition into the cell layer to form a collagenous extracellular matrix. The addition of certain growth factors and the addition of a thin layer of a certain volume exclusion agent on top of the cells dramatically enhances the conversion of procollagen to collagen and will increase the amount of collagen and extracellular matrix associated with the cells. This invention advances bioengineering of connective tissues for medical applications that require an extensive and functional extracellular matrix with high tensile strength such as those in the cornea stroma, skin, tendons, ligaments, articular cartilage and the intervertebral disks.

Abstract: A preservation solution for organs waiting to be transplanted is disclosed; the method of using the solution in a transplantation procedure is also disclosed. The preservation solutions comprise a balanced isotonic aqueous solution comprising sodium, potassium, calcium, magnesium and bicarbonate ions in a physiologically acceptable amount, together with an effective amount of a mutein of the C5a anaphylatoxin which is a C5a receptor antagonist wherein the amino acid residue naturally occurring at sequence position 69 is mutated.

Abstract: Disclosed herein, in certain instances, are tissue grafts derived from UCAM. Further disclosed herein, in certain instances, are use for tissue grafts derived from UCAM.

Abstract: A scaffold material for wound care and/or other tissue healing applications and methods for making the same is described. The scaffold material is constituted of a decellularized extracellular matrix from fish skin. The scaffold material may also include lipids from the lipid layer of the fish skin. Methods for making and using the scaffold material are also described.

Abstract: Method for manufacturing a tissue-engineered construct, such as a heart valve, comprising the steps of providing a-cell-seeded scaffold in a bioreactor chamber which bioreactor chamber is divided by the cell-seeded scaffold into a first compartment and a second compartment, subjecting the cell-seeded scaffold to a flow of nutrient medium within the bioreactor chamber for developing the cell-seeded scaffold to a tissue structure and next to the tissue construct, applying a dynamic pressure difference to the developing tissue structure by the flow of nutrient medium to induce dynamic strain on the tissue structure.

Abstract: The present invention provides a pancreatic islet isolation method comprising the steps of (1) injecting a protection solution containing a protease inhibitor into the pancreatic duct of an procured pancreas; (3) digesting the pancreas into which the protection solution has been injected; and (4) purifying the digested pancreatic tissue using a purification solution containing a density gradient reagent. The present invention also provides a protection solution for injection into the pancreatic duct, a pancreas preservation solution for the two-layer method, and an islet purification solution.

Abstract: A method to increase the time a donated organ will remain viable prior to transplantation, where the method includes infusing into a human patient declared brain dead, using a first intravenous line, a fluorocarbon fluid comprising a chain length from 1 to about 20 carbon atoms, and optionally synchronously with said infusing, exsanguinating said patient using a second intravenous line.

Abstract: A method is described and disclosed for harvesting and preparing porcine hearts that may be used, among other things, as an improved analog of the human heart in cardiac simulator systems for training surgical personnel for performing beating heart surgery.

Abstract: Provided herein are compositions and methods for disrupting at least one reward-related behavior in an individual through the use of light-responsive opsin proteins used to control the polarization state of the cholinergic interneurons of the nucleus accumbens or the striatum.

Abstract: The invention provides, in various embodiments, systems, devices and methods relating to ex-vivo organ care. In certain embodiments, the invention relates to maintaining an organ ex-vivo at near-physiologic conditions.

Abstract: This application describes compositions, methods of treatment, and methods of manufacturing a medicament for reducing injury or damage to cells, tissues or organs during ischemia, reperfusion, or following ischemia or trauma. The methods for reducing damage to a cell, tissue or organ comprise administering an effective amount of a composition including (i) a potassium channel opener or agonist and/or adenosine receptor agonist; and (ii) an antiarrhythmic agent. The methods may further include postconditioning the cell, tissue or organ.

Abstract: A method of preserving functionality of an organ. The method includes removing a whole organ and associated vasculature, cryo-preserving the whole organ, allowing a period of time to elapse, thawing the whole organ including vasculature and introducing the whole organ into a recipient so that the organ is supplied with blood by vasculature belonging to the recipient. Further disclosed is a method of preserving fertility of a patient undergoing a treatment expected to cause sterility. The method include removing a whole gonadal organ from the patient, cryo-preserving the whole gonadal organ, conducting the treatment and waiting for an effect thereof to subside, thawing the whole gonadal organ and introducing the whole gonadal organ where it is supplied with blood by the vasculature system of the patient.

Abstract: The invention provides methodologies and apparatus for producing a cellular soft-tissue implants, both in small quantities and in commercializable quantities. Such soft-tissue implants include vascular graft substitutes. An acellular graft is produced by subjecting the tissue sample to an induced pressure mediated flow of an extracting solution, followed by inducing a pressure mediated flow of a treating solution, then washing the treated tissue to produce the acellular graft. The acellular grafts produced are uniform and nonimmunogenic. The inventive method allows for the production of multiple decellularized soft tissue implants, where processing time is significantly less than prior art processes and the number of implants produced per day is increased over prior art processes. In clinical use, the decellularized grafts produced exhibit significantly improved in long-term durability and function.

Abstract: A demineralized bone matrix is produced by a process in which a bone body is placed in a first processing solution comprising an acid to demineralize the bone body. The bone body is periodically removed from the first solution at specific time intervals to perform at least one test, such as a compression test, on a mechanical property of the bone body. When the test yields a desired result, the bone body is exposed to a second processing solution that is less acidic than the first, thus minimizing the exposure of the bone body to the harsh acidic conditions of the demineralization phase of the process.

Abstract: The present invention relates to blood products, and more particularly to compositions comprising a modified oxygenated hemoglobin having a high affinity for oxygen and methods for making such compositions. Such compositions according to the present invention have better stability to auto oxidation and superior oxygen carrying characteristics.

Abstract: Methods and systems for preserving tissues in situ using critical point drying are disclosed. Such methods and systems are particularly applicable to the preservation of a deceased body, such as a deceased person or animal, with or without removal of internal tissues or organs. A fixative can be perfused through the vascular system of the body while blood is removed from the body. The exterior of the body can also be immersed in a bath of fixative. The fixative in the vascular system and the bath can be replaced by subsequent washes of buffer, de-ionized water, and/or alcohol. The alcohol-infused and fixated body can be disposed in a pressure chamber and subjected to a critical point drying process using carbon dioxide. After the critical point drying process, the body is in a preserved state.

Abstract: The invention provides methodologies and apparatus for producing devitalized soft-tissue implants where the implant retains metabolically non-viable and/or reproductively non-viable cells, and preferably retains large molecular weight cytoplasmic proteins, such implants produced both in small quantities and in commercializable quantities. Such soft-tissue implants include vascular graft substitutes. A devitalized graft is produced by subjecting the tissue sample to an induced pressure mediated flow of an extracting solution, optionally followed by inducing a pressure mediated flow of a salt solution, then washing the tissue to produce the devitalized graft. The devitalized grafts produced are uniform and non-immunogenic. The inventive method allows for the production of multiple devitalized soft tissue implants, where processing time is significantly less than prior art processes and the number of implants produced per day is increased over prior art processes.

Abstract: In a process of fabricating a tissue array, a tissue block is sliced to obtain sheet-form pieces of tissue, and each of the sheet-form pieces is closely rolled around a guide member to form a spiral shape tissue around the guide member. Then, the spiral shape tissues are inserted in an axial direction into holes arrayed in a base block.

Abstract: Subpopulations of spore-like cells expressing specific cell surface and gene expression markers are provided. In one embodiment, the cells express at least one cell surface or gene expression marker selected from the group consisting of Oct4, nanog, Zfp296, cripto, Gdf3, UtF1, Ecat1, Esg1, Sox2, Pax6, nestin, SCA-1, CD29, CD34, CD90, B1 integrin, cKit, SP-C, CC10, SF1, DAX1, and SCG10. Also provided are methods for purifying a subpopulation of spore-like cells of interest from a population of spore-like cells, and methods for inducing differentiation of the isolated spore-like cells into cells of endodermal, mesodermal or ectodermal origin. The spore-like cells can be used to generate cells originating from all three germ layers and can be used to treat a patient who has a deficiency of functional cells in any of a wide variety of tissues, including the retina, intestine, bladder, kidney, liver, lung, nervous system, or endocrine system.

Abstract: A device is provided for securing a tissue sample from biological material. The tissue sample is housed in bottom and top platens that are configured to promote fluid communication between the tissue sample and the exterior environment to permit transport or cryogenic fluid to contact the sample. Additionally, diskette assemblies may be provided within the platens that permit sub-samples to be separated without directly handling the tissue sample. The diskette assemblies may also be configured to promote fluid communication with the sub-sample housed therein.

Abstract: Embodiments of the present disclosure provide for three-dimensional (3D), prevascularized, engineered tissue constructs, 3D prevascularized engineered tissue models of cancer, and bioreactors and bioreactor arrays including the tissue constructs. The present disclosure also provides methods of making the tissue constructs, methods of using the tissue constructs, methods of drug discovery using the tissue constructs and/or cancer models, and the like.

Abstract: Compositions, kits, cells and methods for treating cardiovascular (e.g., myocardial ischemia and heart failure), immunological, and inflammatory diseases or disorders involve the use of the mature and precursor sequences of microRNAs 142-5p, 142-3p, 17-5p, 17-3p, 374, and 20a, and of antisense molecules complementary to these sequences, to manipulate processes relevant to, for example, the cardiac response to stress, including survival signaling, angiogenesis, stem cell differentiation along muscle or vascular lineages, and repression or promotion of cardiac myocyte growth. Also described are methods to treat cardiovascular, immunological and inflammatory diseases by engineering cells containing specific micro-RNAs or antagomirs against specific mRNAs. The engineered cells can then be used to treat patients with such diseases by autologous stem cell therapy.

Abstract: The present invention relates to a method of modulating apoptosis of a granulosa cell. The method includes one or more of the following steps: (i) modulating the concentration and/or activity of BMP-15 and/or BMP-6 that the granulosa cell is exposed to; (ii) modulating activity of a BMP-15 dependent signalling pathway in the granulosa cell; and (iii) modulating activity of a BMP-6 dependent signalling pathway in a granulosa cell.

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 to 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: The invention relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the invention relates to inhibitors of NADPH-oxidase.

Abstract: A reduced dose inseminate and method for producing and using such reduced dose inseminate to fertilize the eggs of a female animal by artificial insemination with fewer sperm cells than compared with conventional dose inseminates.

Abstract: The invention is related to compounds for prevention of cell injury or protection of cells. The compounds are involved in the maintenance or the increase of hydrogen sulphide in cells, which results in a protection of the cells or the prevention of cell injury. The compounds of the invention can be used in cell culture and tissue culture techniques. They can also be used in several medical conditions such as ischemia, reperfusion and hypothermia, or for preserving organs which are used for transplantation.

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. 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: The invention relates to a liver organoid, uses thereof and method for obtaining them.

Abstract: Methods for increasing the efficiency of target tissue penetration of an adeno-associated virus (AAV) vector in a patient are provided. In some aspects, the methods involve inhibiting the interaction of the serum protein galectin 3 binding protein (G3BP) with AAV vector. Further provided are methods for reducing tissue distribution of a virus or for neutralizing a virus harbored by an organ destined for transplant, or newly transplanted, by administering a composition comprising G3BP.

Abstract: Methods to reduce damage to organelles, cells, tissues, organs and organ systems or components thereof caused by strain due to mechanical stress, including stretch stress and shear stress, are provided. The methods involve treating the organelles, cells, tissues, organs, and organs systems or components thereof (such as veins used for grafts in bypass surgery) with PX-18 and related compounds. Treatment with PX-18 and related compounds reduces damage due to stress and improves the functioning of the cells, tissues, organs or organs systems or components thereof. For example, the methods prevent the buildup of atherosclerotic plaque in transplanted (grafted) veins after coronary bypass surgery.

Abstract: The present invention relates to a method for arresting, protecting and/or preserving an organ which includes administering effective amounts of (i) a potassium channel opener or agonist and/or an adenosine receptor agonist and (ii) local anaesthetic to a subject in need thereof. The present invention also relates to a method for arresting, protecting and/or preserving an organ which comprises adding a composition which includes effective amounts of (i) a potassium channel opener or agonist and/or an adenosine receptor agonist and (ii) a local anaesthetic to the organ. The present invention further provides a pharmaceutical or veterinary composition which includes effective amounts of (i) a potassium channel opener or agonist and/or an adenosine receptor agonist and (ii) a local anaesthetic.

Abstract: Tissue matrices having anti-microbial properties are provided. In certain embodiments, the tissue matrices include cationic anti-microbial agents that form a stable bond with the tissue matrices without adversely affecting the biologic properties of the tissue matrices.

Abstract: A method of treating tissue, including organs, with electromagnetic energy to decrease the fat content of the tissue comprises the steps of providing a source of electromagnetic energy, and subjecting adipose cells to the source of electromagnetic energy at hypothermic conditions. The tissue may be harvested and in an isolated state, such as being placed in an organ preservation system. Electromagnetic energy between 600 nm to 700 nm is used for treatment. During treatment, target tissue such as a harvested organ is subject to perfusion.

Abstract: A bag includes an organ transporter compartment to contain an organ transporter disposed in the transporter compartment. The bag may include openings to access portions of the organ transporter, such as a battery or power cable, when the organ transporter is disposed in the bag. The bag may also include a frame and handles. The handles may include structure adapted to mate with handles on the organ transporter. The bag may also include a single cover that provides access to multiple compartments with their own internal covers. Also, the bag may include windows to view documents stored in the bag and/or to view and/or display control panels on the organ transporter.

Abstract: Disclosed herein is a method for measuring the contractility of intestinal tissue upon treatment with GLP-2 or a GLP-2 ligand. Also disclosed is an assay which directly measures the activity of GLP-2 or GLP-2 ligands ex vivo and permits the screening of putative GLP-2 ligands in native tissue.

Abstract: The present invention relates to a retinal pigment epithelial stem cell isolated from a posterior region of the retinal pigment epithelium of an adult mammal. The invention also relates to a method of inducing differentiation of retinal epithelial stem and progenitor cells in vitro, wherein the cells of the invention are highly plastic, multipotential stem cells. The invention also includes methods for the treatment of retinal diseases and vision loss involving the transplantation of retinal pigment epithelial stem cells or cells differentiated from retinal pigment epithelial stem cells to the retina of a patient in need of treatment.

Abstract: The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer or a mixture of stereoisomers in any proportion, in particular a mixture of enantiomers, and particularly a racemate mixture, as well as to their process of preparation, their use in the peptide synthesis, said peptide and the use of said peptide.

Abstract: A method is provided for preparing a tissue implant for implantation. The method includes treating a pericardium tissue material, which has been harvested from a donor and rendered essentially acellular, with a chlorine dioxide treatment solution; and thereafter treating the pericardium tissue material with an antioxidant solution, which comprises ascorbic acid or a salt thereof.

Abstract: A portable apparatus for collection and processing of human biological material containing adipose, such as extracted during a lipoplasty procedure, is useful for multi-step processing to prepare a concentrated product (e.g., stromal vascular fraction) or a fat graft composition. The apparatus has a container with a containment volume with a tissue retention volume and a filtrate volume separated by a filter and with a tapered portion to a collection volume for collecting concentrate product. Inlet and suction ports provide access to the tissue retention volume and filtrate volume, respectively, and an extraction port provides versatile access for removal of target processed concentrate material or fat graft material, which access may be via a lumen through a rotatable mixer shaft. Access ports may be configured for access only from above the container. The apparatus is incorporatable into a variety of assemblies, systems, kits, methods and uses.

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: This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that is effective to fix the phosphoproteins, and that has a sufficient water content to be soluble for a stabilizer and/or a permeability enhancing agent); (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g.

Abstract: The present invention relates to a method of reducing injury to cells, a tissue or organ to be explanted from a body and upon implantation into a body by administering a composition to the cell, tissue or organ, including: (i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and (ii) an antiarrhythmic agent. The invention also provides a composition for reducing injury to vasculature ex vivo including: (i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and (ii) an antiarrhythmic agent.

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: This invention relates to the production of biomaterials with variable stiffness by subjecting a gel which varies in at least one dimension to plastic compaction. These biomaterials may be useful, for example, for the directional control or guidance of cells within tissue equivalent implants.