Abstract: A synthetic scaffold for replacing at least a portion of an airway includes an airway mold, one or more structural ribs on the airway mold, and a non-structural wall. Each of the one or more structural ribs is formed from a first material and the non-structural wall is formed from a second material. The non-structural wall coats the airway mold and forms a conduit that incorporates the one or more structural ribs.

Abstract: Provided are methods of the production of patterned 3-dimensional biopolymer scaffolds containing living cells. The methods include selective photopolymerization of biopolymers to create patterned structures and the patterning of cells within relatively homogenous slabs of biopolymer using dielectrophoresis. Also provided are patterned 3-dimensional biopolymer scaffolds generated by the methods and their use.

Abstract: This present invention provides novel methods for deriving embryonic stem cells and embryo-derived cells from an embryo without requiring destruction of the embryo. The invention further provides cells and cell lines derived without embryo destruction, and the use of the cells for therapeutic and research purposes. It also relates to novel methods of establishing and storing an autologous stem cell line prior to implantation of an embryo, e.g., in conjunction with reproductive therapies such as IVF.

Abstract: Described is a scaffold that is strong enough to resist forces that exist inside a body, while possessing biocompatible surfaces. The scaffold is formed of a layer of mesh (e.g., Stainless Steel or Nitinol) that is tightly enclosed by a multi-layer biological matrix. The biological matrix can include three layers, such a first layer (smooth muscle cells) formed directly on the metal mesh, a second layer (fibroblast/myofibroblast cells) formed on the first layer, and a third layer (endothelial cells) formed on the second layer. The scaffold can be formed to operate as a variety of tissues, such as a heart valve or a vascular graft. For example, the mesh and corresponding biological matrix can be formed as leaflets, such that the scaffold is operable as a tissue heart valve.

Abstract: The present invention relates to a culture support for cultivating hematopoietic stem cells (HSCs) and/or hematopoietic progenitors (HPs), comprising a calcium biomaterial, osteoclasts, endothelial cells and mesenchymatous stem cells (MSCs) and/or osteoblasts and/or adipocytes. The present invention also relates to a method for preparing such a culture support, and an in vitro HSC and/or HP cultivation method. The use of such a culture support for studying cellular mechanisms involved in hematopoiesis and/or differentiation of HSC/HPs and/or for studying the efficacy and/or the toxicity of a medicament candidate is also described.

Abstract: The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Abstract: A process for producing a cultured multi-layered skin cell sheet is provided.

Abstract: Co-culturing of mesenchymal stem cells or tissues comprising mesenchymal stem cells with myocytes or myocyte containing tissues provide for the long term culture and expansion of myocytes. The co-culture gives rise to three-dimensional functioning cardiac tissue grafts or constructs.

Abstract: A cell culture substrate is used comprising a photopolymerization initiator immobilized on a surface of the cell culture substrate, and a linear polymer immobilized on a part or the entirety of the surface via the photopolymerization initiator, and wherein the photopolymerization initiator is thioxanthone. Thereby, advantageously, a single type or multiple types of cells are efficiently cultured on specific regions of the culture substrate, and efficiently detached only by changing temperature on the surface of the substrate.

Abstract: In some embodiments, the present disclosure provides a method for fabricating a three-dimensional artificial cardiac patch construct. In some embodiments, such method includes the steps of coating a substrate with an organic polymer; allowing the organic polymer coating to air dry; mounting anchors on the organic polymer coating; and sterilizing the organic polymer coating and the anchors. In further embodiments, the method includes the steps of forming a biodegradable gel-based support scaffold on top of the organic polymer coating and seeding the biodegradable gel-based support scaffold with neonatal cardiac cells. In yet further embodiments, the method comprises culturing the neonatal cardiac cells in vitro to form a real cardiac layer, under culture conditions that are suitable for the cells to self-organize into a monolayer and detach from the substrate to form the three-dimensional cardiac patch.

Abstract: The invention provides a method for transferring cells to carriers, including: (a) providing a hydrophobic cell culture container or a cell culture container coated with a hydrophobic material on a bottom thereof; (b) adding carriers which are more hydrophilic than the hydrophobic cell culture container or hydrophobic materials and a culture medium containing cells into the hydrophobic cell culture container or the cell culture container coated with the hydrophobic material on the bottom thereof; and (c) culturing the cells, wherein the cells attach to the carriers and grow.

Abstract: Disclosed herein is the finding that treatment with a ROCK inhibitor increases proliferation and induces immortalization of primary keratinocytes. Accordingly, provided is a method of immortalizing primary keratinocytes by exposure to a ROCK inhibitor. Also provided are immortalized primary keratinocytes produced by the described method, as well as organotypic tissue equivalents and cell cultures comprising the immortalized primary keratinocytes. Furthermore, ROCK inhibitor-treated cells show a greatly increased ability to support viral DNA replication of both “low risk” and “high risk” HPV genomes, indicating that ROCK inhibitors will be useful for studying the life cycles of a wide range of HPVs.

Abstract: Methods and devices for applying hemodynamic patterns to human/animal cells in culture are described. Hemodynamic flow patterns are measured directly from the human circulation and translated to a motor that controls the rotation of a cone. The cone is submerged in fluid (i.e., cell culture media) and brought into close proximity to the cells. Rotation of the cone creates time-varying shear stresses. This model closely mimics the physiological hemodynamic forces imparted on endothelial cells in vivo. A TRANSWELL coculture dish (i.e., a coculture dish comprising an artificial porous membrane) may be incorporated, permitting two, three, or more different cell types to be physically separated within the culture dish environment. In-flow and out-flow tubing may be used to supply media, drugs, etc. separately and independently to both the inner and outer chambers. The physical separation of the cell types permits each cell type to be separately isolated for analysis.

Abstract: The present invention relates to a method for producing artificial skin, comprising: adding a matrix metalloproteinase inhibitor and a heparanase inhibitor to an artificial skin formation culture medium comprising human epidermal keratinocytes and human dermal fibroblasts, culturing the cells in the artificial skin formation culture medium, and forming artificial skin.

Abstract: The present invention provides methods and kits for measuring a cell-mediated immune (CMI) in a small volume of whole undiluted blood collected from a subject. In particular, the methods are for measuring responses in undiluted whole blood samples having a volume of, for example, 50 ?l to 500 ?l. Thus, capillary sampling and rapid testing of subjects including pediatric, adult or geriatric human subjects are facilitated.

Abstract: Immunogenic peptides from tumor associated stromal cell antigens, including combinations of such peptides, are disclosed herein. In some examples the peptides are useful for methods of eliciting an immune response. In additional examples the peptides are useful for methods of treating cancer. Methods for decreasing vascularization of a tumor using a Protein Delta Homolog 1 (DLK1) protein or a nucleic acid encoding the protein are also disclosed.

Abstract: The present invention relates to tissue engineered compositions and methods comprising nanotopographic surface topography (“nanotopography”) for use in modulating the organization and/or function of multiple cell types.

Abstract: This invention concerns HY epitopic polypeptides specifically presented by the HLA-DR7 molecule, a method for preparing these epitopic polypeptides, isolated T-lymphocytes capable of specifically recognizing an epitope from these polypeptides or from a polypeptide comprising the complete sequence of the protein encoded by the RPS4Y gene and presented by the HLA-DR7 molecule expressed on the surface of antigen-presenting cells, a method for preparing these T-lymphocytes, as well as the use of these epitopic polypeptides and these T-lymphocytes as medicaments, in particular for the treatment of cancers of immune cells.

Abstract: The present invention provides a method of obtaining aggregates containing a rostral hypothalamus tissue and a rostral head ectodermal tissue, a hypophysis precursor tissue and a hypophysis hormone producing cell, by using a serum-free medium (preferably substantially free of growth factor and insulins), forming homogeneous aggregates of stem cells from pluripotent stem cells such as ES cell and the like, which are plated at a high cell concentration, and subjecting the formed aggregates to floating-culture.

Abstract: The disclosure provides reagents, methods, and kits, for treating melanoma. The reagent encompasses interferon-gamma (IFN-gamma) responsive melanoma cells, where the cells are autophagic and non-apoptotic melanoma cells, and where the cells express MHC. Class II. In another aspect, the reagent encompassed dendritic cells loaded with the IFN-gamma responsive, non-apoptotic, MHC Class II-expressing melanoma cells.

Abstract: According to embodiments, a method of producing insulin-producing tissues (IPTs) by culturing comprises: preparing non-endocrinal epithelial cells (NEECs) and vascular endothelial cells (VECs), which have been isolated or originated from postnatal pancreata, preferably by capturing of NEECs by collagen; culturing in vitro the NEECs and the VECs at least partly separately from each other; and then generating in vitro a tissue complex (IPTs) that contains both the NEECs and the VECs. In another embodiment, the native islet cells are seeded on a monolayer of VECs that have preferably been separately cultured and purified. In a further embodiment, a method of enriching NEECs comprises: culturing NEECs adhering to a container or substrate; removing NEECs by treating with a tissue-dissociation enzyme to leave left-over cells (LOCs) still attached on the container or substrate; and culturing NEECs in a medium conditioned by, or in the presence of the LOCs.

Abstract: This invention relates to methods of expanding T regulatory cells through OX40L and Jagged-1 induced signaling. The methods can be used for treating autoimmune diseases.

Abstract: A composition for delivery of an angiogenesis inducing agent, including a temperature-sensitive liposome, a vascular cell-specific antibody, and an angiogenesis inducing agent, a tissue culture obtained using the composition, an artificial tissue including the tissue culture, and a method for preparing an artificial tissue are provided.

Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.

Abstract: A method for forming neuromuscular junctions includes forming functional neuromuscular junctions between motoneurons and muscle cells by co-culturing one or more human motoneurons and one or more human muscle cells in a substantially serum-free medium. A synthetic mammalian neuromuscular junction includes a human motoneuron functionally linked to a human muscle cell in a substantially serum-free medium. An artificial substrate may be used to support the one or more neuromuscular junctions.

Abstract: The invention provides compositions and methods useful for treating wounds and enhancing wound healing, particularly for diabetic wound healing. One embodiment provides a method of treating a wound comprising administering to a subject in need thereof a therapeutically effective amount of adipose tissue derived stem cells to treat said wound, wherein the cells are cultured in the absence of serum prior to the administration to said subject. Another embodiment provides a method of treating a wound comprising administering to a subject in need thereof a therapeutically effective amount of adipose tissue derived stem cells to treat said wound, wherein the cells are cultured to induce the formation of at least one self-organizing mesenchymal blastema (SOMB) prior to the administration to said subject, wherein said SOMB is formed by culturing adipose tissue derived stem cells in hanging droplets.

Abstract: The present invention provides isolated epitope peptides derived from TOPK and immunogenic fragments thereof have an ability to induce cytotoxic T lymphocytes (CTLs) and thus are suitable for use in cancer immunotherapy, more particularly as cancer vaccines. The peptides of the present invention encompass both of peptides including a TOPK-derived amino acid sequence and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted and/or added, provided such modified versions have CTL inducibility. Further provided are polynucleotides encoding any of the aforementioned peptides as well as pharmaceutical compositions that include any of the aforementioned peptides or polynucleotides. The peptides, polynucleotides, and pharmaceutical compositions of this invention find particular utility in either or both of the treatment and prevention of a number of cancers.

Abstract: The present invention provides a method of inducing myelination of isolated motoneurons by preparing a non-biological substrate having thereon a covalently attached monolayer of DETA; depositing isolated motoneurons on the substrate in a defined serum-free medium; plating isolated Schwann cells cultured in the defined serum-free medium onto the motoneurons, thereby initiating a co-culture; and passaging the co-culture as necessary into fresh, defined serum-free medium supplemented with L-ascorbic acid at least until the motoneurons form Nodes of Ranvier indicative of myelination. The invention also includes a method of testing for new drugs effective in demyelinating diseases. Additionally, cellular products provided by the invention include an isolated motoneurons myelinated or remyelinated in vitro according to the methods disclosed.

Abstract: The present invention provides peptides having an amino acid sequence as set forth in SEQ ID NO: 19, 22, 30, 34, 344, 358, 41, 44, 46, 48, 78, 376, 379, 80, 100, 101, 110, 111, 387, 112, 394, 114, 116, 117, 121, 395, 133, 135, 137, 426, 143, 147, 148, 149, 150, 152, 153, 154, 156, 160, 161, 162, 163, 166, 174, 178, 186, 194, 196, 202, 210, 213, 214, 217, 223, 227, 228, 233, 254, 271, 272 or 288, as well as peptides having the above-mentioned amino acid sequences in which 1, 2, or several (e.g., up to 5) amino acids are substituted, deleted, or added, provided the peptides possess cytotoxic T cell inducibility. The present invention also provides drugs for treating or preventing a disease associated with over-expression of the CDH3, EPHA4, ECT2, HIG2, INHBB, KIF20A, KNTC2, TTK and/or URLC10, e.g. cancers containing as an active ingredient one or more of these peptides. The peptides of the present invention find further utility as vaccines.

Abstract: The present invention provides a vaccine for the prophylactic or therapeutic treatment of a tumour in a mammalian subject, as well as methods of using the vaccine, including in treatment of tumours and in generating a CTL response. The vaccine comprises a plurality of nanoparticles and a pharmaceutically acceptable carrier, salt or diluents.

Abstract: A method is provided, including obtaining a population of antigen-presenting cells, enriching a population of stem/progenitor cells within a larger population of cells, activating the population of antigen-presenting cells and, following the activating, inducing at least one process selected from the group consisting of: differentiation, expansion, activation, secretion of a molecule, and expression of a marker, by exposing the enriched stem/progenitor cell population to the population of antigen-presenting cells. Other applications are also described.

Abstract: The present disclosure provides methods of generating neural stem cells from differentiated somatic cells. The present disclosure also provides induced neural stem cells generated using a subject method, as well as differentiated cells generated from a subject induced neural stem cell. A subject neural stem cell, as well as differentiated cells derived from a subject neural stem cell, is useful in various applications, which are also provided in the present disclosure.

Abstract: The invention provides a method of co-culturing mammalian muscle cells and mammalian motoneurons. The method comprises preparing one or more carriers coated with a covalently bonded monolayer of trimethoxysilylpropyl diethylenetriamine (DETA); suspending isolated fetal mammalian skeletal muscle cells in serum-free medium according to medium composition 1; suspending isolated fetal mammalian spinal motoneurons in serum-free medium according to medium composition 1; plating the suspended muscle cells onto the one or more carriers at a predetermined density and allowing the muscle cells to attach; plating the suspended motoneurons at a predetermined density onto the one or more carriers and allowing the motoneurons to attach; covering the one or more carriers with a mixture of medium composition 1 and medium composition 2; and incubating the carriers covered in the media mixture.

Abstract: Methods of promoting liver morphogenesis prior to the functioning of blood vessels by culturing liver cells with endothelial cells is provided. Also provided are cell cultures and method of promoting vasculogenesis of liver tissue by contacting liver cells with endothelial cells.

Abstract: Methods of regenerating tissue using progenitor cells in combination with primary cells from a target tissue are disclosed. In particular, progenitor cells catalyze proliferation and tissue production by primary cells allowing the use of fewer primary cells from a target tissue for effective tissue regeneration. Cell-based therapies combining progenitor cells and primary cells can be used for repair and regeneration of damaged tissue and organs for treating bodily injuries and degenerative diseases. For example, adipose-derived stem cells and neonatal articular chondrocytes, co-encapsulated in mixed or bilayered cultures in a hydrogel comprising chondroitin sulfate methacrylate and poly(ethylene)glycol diacrylate, generated cartilage that could be used for treatment of traumatic injuries or diseases involving cartilage degeneration.

Abstract: The invention relates to the field of medical science, in particular to technology directed at repairing defects in living, preferably human, tissue. The present invention provides a method for inducing differentiation of multipotent cells to a desired cell type, as well as a method for repairing a tissue defect in a human or animal patient using the concept of said method for inducing differentiation of multipotent cells. The invention further relates to a kit for carrying out the method for repairing a tissue defect.

Abstract: The invention relates to novel artificial antigen presenting cells (aAPCs). The aAPC comprises at least one stimulatory ligand and at least one co-stimulatory ligand where the ligands each specifically bind with a cognate molecule on a T cell of interest, thereby mediating expansion of the T cell. The aAPC of the invention can further comprise additional molecules useful for expanding a T cell of interest. The aAPC of the invention can be used as an “off the shelf” APC that can be readily designed to expand a T cell of interest. Also, the aAPC of the invention can be used identify the stimulatory, co-stimulatory, and any other factors that mediate growth and expansion of a T cell of interest. Thus, the present invention provides powerful tools for development of novel therapeutics where activation and expansion of a T cell can provide a benefit.

Abstract: Disclosed herein are cell preparations useful for modulating various peripheral immune functions, methods for making said cell preparations, and methods for their use.

Abstract: Isolated peptides composed of the amino acid sequence of SEQ ID NO: 33 or fragments thereof that bind to HLA antigens and have cytotoxic T lymphocyte (CTL) inducibility and thus are suitable for use in the context of cancer immunotherapy, more particularly cancer vaccines are described herein. The present invention further provides peptides that include one, two, or several amino acid insertions, substitutions or additions to the aforementioned peptides or fragments, but yet retain the requisite cytotoxic T cell inducibility. Further provided are nucleic acids encoding any of these aforementioned peptides as well as pharmaceutical agents, substances and compositions including any of the aforementioned peptides or nucleic acids. The peptides, nucleic acids, pharmaceutical agents, substances and compositions of this invention find particular utility in the treatment of cancers and tumors.

Abstract: Human progenitor T cells that are able to successfully engraft a murine thymus and differentiate into mature human T and NK cells are described The human progenitor T cells have the phenotype CD34+CD7+CD1a?CD5? or CD34+CD7+CD1a?CD5+ and are derived from human hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells b\ coculture with cells expressing a Notch receptor ligand (OP9-DL1 or OP9-DL4) Such cells are useful in a variety of applications including immune reconstitution, the treatment of immunodeficiencies and as carriers for genes used in gene therapy.

Abstract: Provided herein are pharmaceutical and transplant compositions and methods related to the treatment and prevention of diabetes. More specifically, the compositions and methods are related to activation of glial derived neurotrophic factor (GDNF) receptors or overexpression of the GFR-?1/c-Ret receptor complex in insulin secreting cells so as to promote cell survival and proliferation.

Abstract: A device, and method of making the device, capable of therapeutic treatment and/or for in vitro testing of human skin. The device may be used on skin wounds for burned, injured, or diseased skin, and provides structures and functions as in normal uninjured skin, such as barrier function, which is a definitive property of normal skin. The device contains cultured dermal and epidermal cells on a biocompatible, biodegradable reticulated matrix. All or part of the cells may be autologous, from the recipient of the cultured skin device, which advantageously eliminates concerns of tissue compatibility. The cells may also be modified genetically to provide one or more factors to facilitate healing of the engrafted skin replacement, such as an angiogenic factor to stimulate growth of blood vessels.

Abstract: A system and method for forming a bone construct include providing bone marrow stromal cells on a substrate without disposing the cells within an exogenous scaffold, and culturing the cells in vitro in osteogenic media such that the cells form a confluent monolayer and detach from the substrate to form a self-organized three-dimensional bone construct. A system and method for forming a ligament construct using fibrogenic media and a system and method for forming a functionally integrated bone-ligament construct are also provided.

Abstract: Disclosed is a microfluidic chip and method using the same. The microfluidic chip comprises a substrate having a surface, and at least a tissue culture area formed on the surface of the substrate. The tissue culture area has a microfluidic channel formed by a plurality of connected geometrical structures (nozzle-type channels) having a predetermined depth. The microfluidic channel has an inlet and an outlet, which are at two ends of the microfluidic channel, for medium inputting and outputting, respectively. Additionally, at least an air-exchange hole is formed on the bottom of the microfluidic channel. By using the microfluidic chip for tissue culture, lateral flow speed and stress can be decreased, so as to prolong survival time of tissues (e.g. liver tissues).

Abstract: The invention provides a method of obtaining a population of antigen-specific T cells from peripheral blood of a host. An embodiment of the method of the invention comprises (i) dividing PBMCs from peripheral blood of a host into more than one sub-population; (ii) contacting the PBMCs with an antigen and IL-2; (iii) obtaining a sample of PBMCs from each sub-population; (iv) identifying an antigen-reactive sub-population by determining by high throughput quantitative PCR the expression of a factor produced by the PBMCs of each sample; (v) dividing the antigen-reactive sub-population into microcultures; (vi) identifying the antigen-reactive microculture; and (vii) expanding the microculture, thereby obtaining a population of T cells specific for the antigen. The invention also provides a population of T cells obtained by the inventive method, a pharmaceutical composition comprising the same, and a method of treating a disease in a host using the pharmaceutical composition.

Abstract: Described herein are cell culture media, kits and methods for preparing cell culture media, and methods for culturing cells, for example, cells of the female reproductive tract, and tumor cells.

Abstract: As described below, the present invention features compositions and methods related to the isolation, culture and therapeutic use of CD31-expressing cells.

Abstract: Methods for purifying very small embryonic-like (VSEL) stem cells from populations of cells suspected of including VSEL stem cells are provided. In some embodiments, the methods include (a) providing a population of cells suspected of including a VSEL stem cell; and (b) isolating a CD45neg/GlyAneg/CD133+/ALDHhigh subpopulation, a CD45neg/GiyAneg/CD133+/ALDlow subpopulation, a CD45neg/Linneg/SSEA-4+/ALDHhigh subpopulation, a CD45neg/Linneg/SSEA-4/AiOlow subpopulation, or any combination thereof from the population, whereby a VSEL stem cell is purified from the population. Also provided are methods for generating in vitro hematopoietic colonies derived from VSEL stem cells and methods for generating lympho-hematopoietic chimerism in a subject.

Abstract: The invention provides a micro-organ composite which comprises a core group of cells and an outer layer of cells, wherein the cells of the core group are mesenchymal cells and the cells of the outer layer are epithelial cells or wherein the cells of the core group are epithelial cells and the cells of the outer layer are mesenchymal cells, and wherein the core group of cells is at least partially encapsulated by the outer layer of cells.

Abstract: As discussed in greater detail herein, isolated epitope peptides derived from MPHOSPH1 bind to an HLA antigen and induce cytotoxic T lymphocytes (CTL) and thus are suitable for use in the context of cancer immunotherapy, more particularly cancer vaccines. The inventive peptides encompass both the above-mentioned MPHOSPH1-derived amino acid sequences and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted or added, provided such modified versions retain the requisite CTL inducibility of the original sequences. Further provided are polynucleotides encoding any of the aforementioned peptides as well as pharmaceutical agents or compositions that include any of the aforementioned peptides or polynucleotides.