195results about "Tissue screening" patented technology

A stromal cell-based three-dimensional cell culture system is prepared which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The living stromal tissue so formed provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and / or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue. For example, and not by way of limitation, the three-dimensional cultures can be used to form tubular tissue structures, like those of the gastrointestinal and genitourinary tracts, as well as blood vessels; tissues for hernia repair and / or tendons and ligaments; etc.

A stromal cell-based three-dimensional cell culture system is provided which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells along with connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. Living stromal tissue so formed provides support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and / or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue. The three-dimensional cultures can be used to form tubular tissue structures, like those of the gastrointestinal and genitourinary tracts, as well as blood vessels; tissues for hernia repair and / or tendons and ligaments. A three-dimensional filamentous tissue having tendon or ligament function is prepared containing fibroblasts and collagen naturally secreted by the fibroblasts attached to and substantially enveloping a three-dimensional filamentous framework.

A multilayer microculture capable of modeling complex in vitro structures such as mammalian tissues and organ structures is provided, along with methods for producing such a microculture and methods of using such microcultures for assaying for modulators of cell-cell interaction, cell migration, cell proliferation, cell adhesion or cellular or organismal physiology. Further provided are methods of identifying hazardous materials such as environmental toxins and pollutants (e.g., carcinogenic compounds), and methods of monitoring organismal physiology.

Disclosed is a cervico-vaginal tissue equivalent comprised of vaginal epithelial cells and immune cells, cultured at the air-liquid interface. The tissue equivalent is capable of being infected with a sexually transmitted pathogen such as a virus (e.g., HIV), a bacteria, a helminthic parasite, or a fungus. The tissue equivalent is also capable of undergoing an allergic-type reaction or an irritant-type reaction. The tissue equivalent is characterized as having nucleated basal layer cells and nucleated suprabasal layer cells, and further as having cell layers external to the suprabasal layer progressively increasing in glycogen content and progressively decreasing in nuclei content. Immune cells of the tissue equivalent are primarily located in the basal and suprabasal layers. Also disclosed are methods for producing the tissue equivalent. The methods involve providing vaginal epithelial cells and immune cells, seeding the cells onto a porous support, and co culturing the seeded cells at the air-liquid interface under conditions appropriate for differentiation. One such method disclosed is for generation of the tissue equivalent in serum free medium. Specific cells from which the tissue equivalent is generated, and also specific preferred components of the medium in which the tissue equivalent is generated are provided. Also disclosed is a cervico-vaginal tissue equivalent produced by the methods disclosed herein.

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.

The present invention provides for an engineered three dimensional (3D) pulmonary model tissue culture which is free of any artificial scaffold.

The present invention generally relates to the field of diagnostic microbiology, and, more particularly, to compositions and methods for detecting and differentiating one or more viruses or other intracellular parasites present in a specimen. The present invention also provides compositions and methods to evaluate the susceptibility of a organisms to antimicrobial agents.

The present invention generally relates to the field of diagnostic microbiology, and, more particularly, to compositions and methods for detecting and differentiating one or more viruses or other intracellular parasites present in a specimen. The present invention also provides compositions and methods to evaluate the susceptibility of a organisms to antimicrobial agents.

The invention relates to a method of in vitro testing of the efficacy of a potentially active substance comprising monitoring the effect of said potentially active substance on an artificial skin, comprising a composite product forming a collagen support comprising at least one porous collagen layer covered on at least one side with a collagen membrane component selected from the group consisting of a collagen membrane prepared by compression of a collagen sponge at a pressure of at least about 50 bar and of a collagen membrane comprising a collagen film prepared by drying a collagen gel separately from the porous collagen layer, thereby providing a reliable method for finding new potentially active substances.

The invention relates to a method of in vitro testing of the efficacy of a potentially active substance comprising monitoring the effect of said potentially active substance on an artificial skin, comprising a composite product forming a collagen support comprising at least one porous collagen layer covered on at least one side with a collagen membrane component selected from the group consisting of a collagen membrane prepared by compression of a collagen sponge at a pressure of at least about 50 bar and of a collagen membrane comprising a collagen film prepared by drying a collagen gel separately from the porous collagen layer, thereby providing a reliable method for finding new potentially active substances.

The invention relates to a construction method for in-vitro three-dimensional human liver tissue. The construction method comprises the following steps: (1) uniformly mixing a solution of seed cells with an aqueous solution of biological ink so as to obtain a cell printing solution; (2) under the control of a computer, uniformly extruding the cell printing solution with a cell printer at a set speed according to a designed path and allowing the cell printing solution to rapidly coagulate at a certain temperature so as to form gel microfilaments, and repeating the above operations so as to finish construction of a multilayer cell structure in a layer-upon-layer scanning manner; (3) subjecting the multilayer cell structure to secondary crosslinking and culturing the multilayer cell structure with a cell culture solution so as to obtain a stable multilayer cell structure; and (4) culturing the stable multilayer cell structure with an induction medium so as to obtain the in-vitro three-dimensional human liver tissue. The method provided by the invention can construct in-vitro three-dimensional human liver tissue with good functionality, and the constructed in-vitro three-dimensional human liver tissue is applicable to fields like treatment of hepatopathy, medicinal development, medicine screening, etc.

The present invention is directed to an in vitro cultured permissive niche, or human bone marrow microenvironment, comprising a scaffold coated with human mesenchymal stem cells and a culture medium, wherein the stem cells are viable and proliferate in culture and the niche is permissive for the establishment of introduced hematopoietic or leukemic cell populations. The present invention is also directed to establishment of a permissive niche in a non-human animal model comprising a scaffold coated with human mesenchymal stem cells introduced into the animal ectopically, wherein the niche and the model are permissive for the establishment of introduced hematopoietic or leukemic cell populations. The implanted scaffold forms an ectopic human bone marrow microenvironment to study the mesenchymal leukemic stem cell niche. In addition, the present invention is directed to methods of using the in vitro cultured human bone marrow microenvironment and the non-human animal model to evaluate an agent for anti-leukemic properties.

The invention relates to the use of CD14+ monocytes for the production of dendritic cells. The invention comprises the use of CD14+ monocytes isolated from peripheral circulating blood for obtaining, by differentiation, at least one mixed population of Langerhans cells and interstitial dendritic cells, both Langerhans cells and interstitial dendritic cells being preconditioned and undifferentiated, and / or differentiated and immature, and / or mature, and / or interdigitated. The invention comprises their use in suspension, monolayer and three-dimensional cell and tissue models. The invention comprises the use of these cells and of these models as study models for the assessment of immunotoxicity / immunotolerance, for the development of cosmetic and pharmaceutical active principles and for the development and implementation of methods of cell and tissue therapy.

The invention discloses an in-vitro recombined human skin epidermis model.A layer of hemidesmosome protein is arranged on the lower surface of a basal cell layer, the upper surface of the basal cell layer is covered with 6-8 spinous cell layers containing short protruding spinous cells, the upper surface of the spinous cell layers is covered with 3-4 granular cell layers containing transparent granular cells, the upper surface of the granular cell layers is covered with a keratinocyte layer, all the cell layers are obviously separated, and the overall barrier function of a lipid composition is approximate to that of human skin.A preparation method comprises the steps of preparation of matrigel particles, screening and amplification of epidermal stem cells, preparation of the basal cell layer, preparation of the spinous cell layers, preparation of the granular cell layers, and maturation and keratinization of the in-vitro recombined epidermis model.The model is applied to evaluation of cosmetics with the human skin barrier repair effect, screening of plant extract with the human skin barrier repair effect, evaluation and detection of irritation of medical apparatus materials on the human skin and detection of irritation of chemicals on the skin.

Leukemia Inhibitory Factor (“LIF”), an LIF analogue, an LIF mimetic and a product capable of stimulating the expression of endogenous LIF, and mixtures thereof are useful, for (i) promoting the multiplication, in vitro, of a population of human skin stem cells and / or epidermal progenitors while maintaining them in an undifferentiated state, and / or for (ii) maintaining and / or increasing their capacity to generate a pluristratified epithelium, in particular a pluristratified epidermis and / or all or some of the skin appendages; also a library or a culture of human undifferentiated skin stem cells and / or epidermal progenitors is obtained in the presence of LIF, as are reconstructed epidermides and / or reconstructed skin, and kits for producing libraries of cells or reconstructed epidermides, and stem cells or reconstructed epidermides are prepared for the treatment of individuals exhibiting damaged skin (individuals suffering from third degree burns and individuals suffering from genetic diseases affecting the skin).

The present invention provides tissue scaffolds, methods of generating such scaffolds, and methods of use of such scaffolds to generate aligned and functional tissues for use in methods including regenerative medicine, wound repair, and transplantation.

The invention provides compositions and methods to generate pilosebaceous units. In one aspect, the invention comprises a biocompatible scaffold and an effective amount of dermal and epidermal precursor cells.

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.

The present invention provides methods and compositions for augmenting organ functions using small-scale matrix implants generated by seeding tissue-specific or undifferentiated cells onto a matrix materials (e.g., a wafer, sponge, or hydrogel). The seeded matrix composition can then be implanted and will develop into an organ-supplementing structure in vivo. Continued growth and differentiation of the seeded cells on the implanted matrix results in the formation of a primitive vascular system in the tissue. The primitive vascular system can then develop into a mature vascular system, and can also support the growth and development of additional cultured cell populations. The seeded matrix system can be used to introduce a variety of different cells and tissues in vivo.

This invention relates to a three dimensional bioengineered sphincter such as a bioengineered internal anal sphincter (IAS) and three-dimensional physiological models of smooth muscle cells. The invention also related to methods for generating a bioengineered sphincter and smooth muscle rings in culture. In addition, the invention provides for methods of using a bioengineered sphincter or bioengineered smooth muscle ring to identify agents that modify contractile force and relaxation in smooth muscle cells.

A neural network is disclosed. The neural network comprises a plurality of optogenetically modified neural cells being three-dimensionally distributed in a hydrogel medium and being disconnected from any solid support having a shear modulus above 1 GPa.

The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.

A cell culture medium for culturing an organoid which comprises at least two members selected from the group consisting of insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2) and epiregulin (EREG), and at least one member selected from components i) to iii): i) a Wnt agonist; ii) a bone morphogenesis protein (BMP) inhibitor; and iii) a transforming growth factor-beta (TGF-beta)inhibitor.

The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the tissues of the immune system in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates and other materials in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system, coupled with disease models to provide a more complete representation of an immune response.

A chimeric skin comprising immortalized human keratinocyte cells cocultured with donor keratinocytes is disclosed.

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

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

Described herein are in vitro cell constructs (or “organoids”) useful as a tumor model, the constructs comprising live tumor cells from a subject. In some embodiments, provided are in vitro cell constructs comprising: (a) a core comprised of live tumor cells; and (b) a shell surrounding (e.g., encapsulating) the core, the shell comprised of live benign cells (e.g., tissue cells, benign or differentiated tumor cells, etc.). Also described herein are methods of making and using such constructs. Further provided are devices useful for evaluating tumor cells in vitro, comprising: (a) a microfluidic device having a chamber, and a channel in fluid communication with the chamber; (b) a live tumor cell construct (e.g., an organoid) in the chamber; (c) a growth media in the chamber and the channel; (d) a pump operatively associated with the chamber and channel and configured for circulating the media from the chamber through the channel and back to the chamber; (e) a microporous membrane (e.g., a TRANSWELL® microporous membrane) in the channel and positioned so that the media flows therethrough.