Abstract: The development and function of living tissues depends largely on interactions between cells that can vary in both time and space; however, temporal control of cell-cell interaction is experimentally challenging. By employing a micromachined silicon substrate with moving parts, herein is disclosed the dynamic regulation of cell-cell interactions via direct manipulation of adherent cells with micron-scale precision. The inventive devices and methods allow mechanical control of both tissue composition and spatial organization. The inventive device and methods enable the investigation of dynamic cell-cell interaction in a multitude of applications, such as intercellular communication, spanning embryogenesis, homeostasis, and pathogenic processes.

Abstract: This invention relates to methods for improved cell-based therapies for retinal degeneration and for differentiating human embryonic stem cells and human embryo-derived into retinal pigment epithelium (RPE) cells and other retinal progenitor cells.

Abstract: RNA interference using small interfering RNAs which target HIF-1 alpha mRNA inhibit expression of the HIF-1 alpha gene. As HIF-1 alpha is a transcriptional regulator of VEGF, expression of VEGF is also inhibited. Control of VEGF production through siRNA-mediated down-regulation of HIF-1 alpha can be used to inhibit angiogenesis, in particularly in diseases such as diabetic retinopathy, age related macular degeneration and many types of cancer.

Abstract: As described below, the present invention features methods for reprogramming somatic cells and related therapeutic compositions and methods.

Abstract: Provided is a method of inducing tubulogenesis in normal endothelial cells comprising co-culturing the normal endothelial cells with tumor cells and forming tubules from the normal endothelial cells.

Abstract: A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

Abstract: The present invention provides a method for preparing a hair dermal papilla cell preparation comprising preparing a cell suspension by removing epidermal tissue from skin tissue and subjecting the resulting dermal tissue fraction to collagenase treatment, and cyropreserving the cell suspension to kill the follicular epidermal cells. The present invention also provides a composition for regenerating hair follicles comprising hair dermal papilla cell and epidermal cells, wherein the ratio of the number of hair dermal papilla cell to the number of epidermal cells is from 1:10 to 10:1.

Abstract: Disclosed is a kit comprising a first component comprising fibrinogen, aprotinin, and a buffered solution, and a second component comprising, fibroblasts, keratinocytes, thrombin, glycerol, human serum albumin, and a buffered solution, wherein the first and second components are comprised in separate sterile containers.

Abstract: The present invention provides a novel approach to the modulation of the immune response, directing it towards specific antigens, away from antigens against which no response is desired. The invention is based on the use of viral immune evasion proteins, such as UL49.5, which block antigen presentation to CD8+ T cells. The viral immune evasion proteins are used for: 1) the induction of tumor-specific or virus-specific immunity in cases where a conventional immune response is absent due to antigen processing defects; 2) the induction of empty MHC class I molecules at the cell surface that can be loaded with peptides of a desired specificity; 3) the inhibition of unwanted immune responses against transplanted tissues or organs, e.g. against islets of Langerhans in type 1 diabetes or allogeneic stem cells, or against self antigens in the case of autoimmunity.

Abstract: The present application relates to a method for modulating the growth state of an lung tissue, or a cell thereof, e.g., by ectopically contacting the tissue, in vitro or in vivo, with a hedgehog therapeutic, a ptc therapeutic, or an FGF-10 therapeutic in an amount effective to alter the rate (promote or inhibit) of proliferation of cells in the lung tissue, e.g., relative to the absence of administration of the hedgehog therapeutic or ptc therapeutic. The subject method can be used, for example, to modulate the growth state of epithelial and/or mesenchymal cells of a lung tissue, such as may be useful as part of a regimen for prevention of a disease state, or in the treatment of an existing disease state or other damage to the lung tissue.

Abstract: The present invention refers to a cell culture system especially for investigating the sensitizing, allergenic and/or irritating effect of substances, comprising a first and a second compartment that can communicate with each other via a permeable interlayer, whereby the first compartment has an epidermis model and the second a cell culture based on immune cells.

Abstract: Described herein are tissue culture plates with permeable tissue culture plate inserts therein, which provides the tissue culture plates with apical chamber and a basolateral chambers, wherein cells are deposited on the permeable tissue culture inserts and essentially all of tissue culture medium has been removed from the apical chambers of the tissue culture plates and the basolateral chambers of the tissue culture plates contain a solidifiable form of cell culture medium. Also described are cells that can be deposited and grown on the described tissue culture inserts, methods for transporting a tissue culture plate with a permeable tissue culture plate insert therein on which cells are deposited. Also described is a kit for transporting the tissue culture plates described above, and corresponding methods of use.

Abstract: The present invention belongs to the field of tissue engineering and specifically relates to a method for obtaining three-dimensional structures for tissue engineering and to the structures obtained by said method. The invention also relates to an ex vivo method for regenerating a tissue using the three-dimensional structures of the invention and to the use of the structures thus treated for their transplanting to the area to be regenerated of the patient.

Abstract: Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

Abstract: The present invention relates to processes for obtaining melanocytes from a cell suspension, in particular from an epidermal cell suspension, by means of a culture vessel, wherein at least a part of the surface of the culture vessel facing the culture space, is modified, in particular functionalized, in particular by means of a low-pressure plasma process. Furthermore, the present invention relates to culture vessels which are modified, in particular functionalized, in particular by means of a low-pressure plasma process and are suitable for obtaining melanocytes and the use of such culture vessels for obtaining melanocytes.

Abstract: Provided are tissue scaffolds colonized by vertebrate cells expressing a transgenic bioactive molecule, where the vertebrate cells are unable to undergo mitosis. Also provided are methods of growing tissue in a mammal and methods of delivering a transgenic bioactive molecule to a tissue of a mammal, using the tissue scaffolds. Additionally, methods of making the tissue scaffolds are provided.

Abstract: The present invention provides a new method for identifying modulators of human orexin-2 receptor without utilizing recombinantly produced nucleic acid molecules encoding human orexin receptor protein. This method combines and utilizes known methods and cell lines selected for their natural expression of orexin-2 receptors to carry out the methods of the present invention. Exemplary methods of the present invention utilize PFSK-1 cells to produce non-recombinant human orexin-2 receptor protein.

Abstract: The invention relates to materials and methods for producing equivalents of tissues of the ocular surface, especially conjunctival tissue equivalents. The method of the invention involves biopsy of an appropriate tissue, primary culture in a certain medium, proliferative culture in a second medium, and differentiative culture in a third medium. The tissue equivalents are typically grown upon a substrate, typically amniotic membrane, which provides ease of handling as one advantage.

Abstract: The present invention relates to a culture system for and a method for propagation of human blastocyst-derived stem cells (hBS cells) upon enzymatic dissociation into a single cell suspension. The culture system for propagation of human blastocyst-derived stem (hBS) cells comprises i) human feeder cells at a density of at least 50,000 cells/cm2, ii) one or more dissociation agents for dissociation of hBS cell colonies into a single cell suspension, and iii) a supportive culture medium, which culture system makes it possible to propagate hBS cells by dissociation of hBS cell colonies into a single cell suspension at each consecutive passage for an extended time period, while maintaining the significant characteristics of hBS cells.

Abstract: A tissue graft construct for use in repairing diseased or damaged tissues is provided. The tissue graft construct comprises a matrix composition selected from the group consisting of liver basement membrane and extracts and hydrolysates thereof, and processed collagen from vertebrate non-submucosal sources, added endothelial cells, and at least one additional preselected, exogenous population of cells which enhance the initiation of vessel-like structures in the grant. The preselected population of cells can be a population of non-keratinized or keratinized epithelial cells or a population of mesodermally derived cells selected from the group consisting of fibroblasts, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, multi-potential progenitor cells, pericytes, osteogenic cells, and any other suitable cell type, preferably selected based on the tissue to be repaired.

Abstract: The present invention relates to a method for obtaining master adult pluripotent stem (MAPS) cells from adult human corneal epithelial tissues. The MAPS cells are obtained on the basis of pluripotent markers. Further the invention provides MAPS cells that are capable of self renewal and differentiation and have characteristics similar to that of human embryonic stem cells. The MAPS cells also retain the ability to differentiate into cells of different lineages. The composition comprising MAPS cells are useful for therapeutic purposes. Further, the invention provides a culture medium for proliferation of MAPS cells.

Abstract: An in vitro skin equivalent includes at least one epidermis equivalent and at least one dermis equivalent, and further includes melanocytes constitutively producing melanin and fibroblasts.

Abstract: Methods and compositions for identifying and isolating dermal papilla cells are described. DP cells can be identified based on corin expression. Isolated DP cells can be used, e.g., to modulate hair growth.

Abstract: The present invention is based on the discovery that teeth primordia can be generated using bone marrow cells and that bone marrow cells may be employed to generate teeth without the need for purification and expansion of a population of cells.

Abstract: Disclosed herein are reagent-cell complexes comprising one or more definitive endoderm cells. Also described herein are compositions for detecting definitive endoderm. Method of enriching, isolating and/or purifying definitive endoderm cells are also disclosed.

Abstract: The expansion of a population of stem cells or progenitor cells, or precursors thereof, may be accomplished by disrupting or inhibiting p21cip1/waf1 and/or p27, cyclin dependent kinase inhibitors. In the absence of p27 activity, progenitor cells move into the cell cycle and proliferate; whereas in the absence of p21 activity, stem cells move into the cell cycle and proliferate without losing their pluripotentiality (i.e., their ability to differentiate into the various cell lines found in the blood stream). Any type of stem cell or progenitor cell, or precursor thereof, including, but not limited to, hematopoietic, gastrointestinal, lung, neural, skin, muscle, cardiac muscle, renal, mesenchymal, embryonic, fetal, or liver cell may be used in accordance with the invention.

Abstract: The invention relates to a composite comprising a semi-permeable barrier layer that is permeable to oxygen and impermeable to moisture; and a scaffold fiber layer formed by electrospinning fibers on one side of the barrier layer.

Abstract: Provided is a composition comprising a primed engineered tissue construct, methods of making the composition, methods of using the composition in dermatologic surgery, and a kit for supplying surgical tissue graft components.

Abstract: Methods and cell culture medium for the generation and maintenance of human pluripotent embryonic stem cells are disclosed. Human embryonic stem cells are cultured with human feeder cell conditioned medium, and the embryonic stem cells maintain their pluripotent phenotype. The human pluripotent embryonic stem cells can be cultured without feeder cells, and in the presence of supplemental growth factors.

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 provides a bioartificial lacrimal gland which contains at least one unit that includes (a) a permeable housing having an interior and an exterior; (b) an outlet connecting the housing interior to the housing exterior; and (c) a population of lacrimal epithelial cells within the housing interior.

Abstract: The present invention relates generally to systems and methods for storing, shipping and using skin equivalents made by organotypic culture. In particular, the present invention relates to systems and methods for producing, transporting, storing and using skin equivalents produced by organotypic culture at reduced temperatures, preferably from 2-8 degrees Celsius. The methods include sterile packaging of the grafts so that the sterility and integrity of the package is maintained until the time of use for grafting purposes.

Abstract: Vectors capable of stably integrating a transgene in the genome of a non-dividing cell or of a slowly-dividing cell, said vector comprising or expressing at least one immortalization molecule and cells immortalized with said vectors.

Abstract: The present invention relates to in vitro cultured skin substitutes, and in particular to improved methods for organotypic culture of skin substitutes. In some embodiments, the dermal equivalent of the skin substitute is lifted to air interface of the culture prior to seeding with keratinocytes. In other embodiments, increased concentrations of collagen are used to form the dermal equivalent. In still other embodiments, optimized media are utilized to maintain the skin equivalents.

Abstract: The present invention provides an animal cell expressing a gene coding a ligand-responsive transcription control factor and securely maintaining a DNA comprising in a molecule, the following genes (a) and (b): (a) a reporter gene connected downstream from a transcription control region, in which said transcription control region substantially consists of a recognition sequence of said ligand-responsive transcription control factor and a minimum promoter which can function in said cell; and (b) a selective marker gene which can function in said cell; provided that the following gene (c): (c) a reporter gene connected downstream from a promoter which transcription activity is unchanged by having said responsive transcription control factor contacted with a ligand of said ligand-responsive transcription control factor, said reporter gene (c) coding a protein which can be differentiated from the protein coded by said gene (a) is not present in said cell and the like.

Abstract: Isolated human multipotent adult stem cell and isolated populations of cells that include human multipotent adult stem cells are disclosed. Human hair-follicle derived multipotent adult stem cells and methods of preparing isolated populations of cells that include human multipotent adult stem cells are disclosed. Isolated human hair-follicle derived multipotent adult stem cell that can differentiate in culture into a neuronal cell, a glial cell, a melanocyte cell, a muscle cell, an osteocyte, a chondrocyte, and a lymphocyte. Isolated human hair-follicle derived multipotent adult stem cell that can grow in cell culture in spheres are disclosed.

Abstract: A method of inducing liver regeneration in a damaged liver tissue region of an individual is provided. The method including the step of providing at least two distinct growth factors to the damaged liver tissue region of the individual, at least one of the at least two distinct growth factors being an angiogenic factor.

Abstract: A method for preparing a human or animal tissue by applying a compressive force to a stack of sheets of living tissue thereby inducing adjacent layers to fuse or adhere to each other. The force is applied in direction normal to the surface of the tissue. A multi-layer tissue produced by the method described above can also possess at least two different types of sheets and/or consist essentially of between two and twelve sheets of living tissue. The method can also be used to prepare a planar tissue that can further be incorporated in a multi-layer tissue construct. The methods and tissues described herein are useful for the preparation of engineered tissues.

Abstract: The present invention provides a cell composition for transplant comprising fibroblasts originating in buccal fat pad.

Abstract: The present invention relates to in vitro cultured skin tissue, and in particular to cultured skin tissue comprising exogenous genes encoding angiogenic growth factors. In some embodiments, the keratinocytes express exogenous angiopoietin-1 or a member of the VEGF family, preferably VEGF-A. In particularly preferred embodiments, the keratinocytes are incorporated into cultured skin tissue.

Abstract: The invention relates to the use of a cultured stem cell to produce a tooth progenitor cell.

Abstract: The invention provides methods of culturing mammalian taste cells, including taste receptor cells. Cells are maintained for a duration of up to three months and longer while maintaining molecular and functional characteristics of mature taste cells. The cells are cultured on coated cell culture vessels and, from first replacement of medium onwards, the medium is replaced in intervals of at least 5 days. The invention further provides isolation and culturing methods of taste cells wherein the time that the cells are exposed to isolation solution and proteolytic enzymes is minimized and the cells are cultured in coated culture vessels with the medium replaced in intervals of at least 5 days from first replacement onwards. The invention further provides cultured taste cells, transfection and assay methods, and taste cell assay buffers with an osmolarity of about 300-320 and pH of about 7.0-7.3.

Abstract: The invention provides compositions and methods for treating tumors that involve increasing the expression of Nod1 and/or the activity of NOD1.

Abstract: The present invention relates to immortal pluripotent stem cells derived from a human leukaemia cell line, preferably a human monocytoid cell line and more preferably the human monocytoid cell line, THP1. The present invention further relates to cell lines derived from the immortal pluripotent stem cell line having the phenotype of cell strains characteristic of human tissues, particularly having a human hepatocyte phenotype, as well as the methods for preparing thereof. The present invention further relates to the use of the derived cell line with a human hepatocytic phenotype for the production of albumin and blood coagulation factors.

Abstract: The invention is the modification of organs, tissues and cells with a storage/reperfusion solution comprising siRNAs specific for genes whose expression is associated with loss of viability or cell damage. The presence of siRNAs in the storage/reperfusion solution minimizes and/or prevents organ, tissue and cell damage such that the organs, tissues or cells can be used for in vivo transplantation. The invention is also directed generally to methods for maintaining organs, tissues and cells in a viable state using the storage/reperfusion solution.

Abstract: The present invention provides isolated apoptotic epithelial scaffolds. The scaffolds find use in promoting re-vascularization of wounded tissues. The present invention also provides isolated or ex vivo tri-layered cell sorted tissues comprised of a bottom layer comprised of an apoptotic epithelial scaffold, a middle layer comprised of mesenchymal cells, and a top layer comprised of non-differentiated epithelial cells. The invention further provides in vitro methods for generating isolated or ex vivo tri-layered cell sorted tissues by exposing cultured mixtures of epithelial and mesenchymal cells to an inflammatory cytokine. Further provided are methods of promoting wound healing and re-vascularization of wounds by contacting wounded tissue with the apoptotic epithelial scaffolds of the invention.

Abstract: A method for obtaining a response of a tissue model system to an activator includes contacting a bio-artificial tissue model system with an activator and measuring cellular mechanical response thereto of at least one of contractile force and tissue stiffness. A method for obtaining a response of a tissue model system to an activator includes contacting a bio-artificial tissue model system with an activator and measuring cellular mechanical response thereto of at least one of contractile force and hysteresis.

Abstract: The present invention provides the use and composition of matter of angiogenic or other growth/cytokine factors expressed by mixtures of allogeneic human cell strains or lines of various types and stages of differentiation. Also provided are unencapsulated preparations (mixed with or applied to extracellular matrix material or synthetic biocompatible substances) for the purpose of temporary application to wounds or defects in the skin or other tissues for the restoration of blood supplying connective tissue to enable organ-specific cells to reestablish organ integrity as well as to inhibit excessive scar formation.

Abstract: The present invention relates to the field of oncology and provides novel compositions and methods for diagnosing and treating pancreatic cancer. In particular, the present invention provides pancreatic cancer stem cells useful for the study, diagnosis, and treatment of solid tumors.

Abstract: The invention is directed to a chemically defined animal cell culture media, and methods for preparing such a medium, wherein the media are suitable for culturing epidermal cells, preferably human epidermal cells, including cells of the hair follicle. The invention further provides for methods of culturing epidermal cells, hair follicles, and skin explants in the media as well as uses of the cell cultures and explant cultures in screening assays.