2121 results about "Fibroblast" patented technology

A cultured skin and a grafting cultured skin sheet are provided, each of which is a cultured reconstructive skin with a high take rate using cells collectable from cells originated from tissue included in an umbilical cord such as tissue included in an umbilical cord originated from a human fetus. The grafting cultured skin stratified sheet is prepared by placing an epithelium sheet on the top surface of a cultured dermis. The cultured dermis includes as components a cultured skin containing cells originated from a tissue included in an umbilical cord, such as umbilical cells, more concretely, umbilical fibroblast cells, being separated and cultured, preferably in a collagen nonwoven fabric. On the other hand, the epithelium sheet is prepared by culturing and stratifying the umbilical cord epithelium cells.

An apparatus for delivering a bioactive material to a subterranean layer of a skin architecture is provided that includes a head including one or more needles that are operable to penetrate a stratum corneum of a skin. A bioactive material is disposed on one or more of the needles, whereby movement of the head operates to pick up the bioactive material and to deliver a portion of the bioactive material to a selected location, the selected location being a dermis, or an epidermis, or both the dermis and the epidermis. In more particular embodiments, the bioactive material is a macromolecule substance that is part of a group of substances, the group consisting of a protein, a vitamin, a gene, a growth agent, a drug, and a peptide. The needles create an injury that triggers collagen production from one or more fibroblasts in the skin.

Pharmaceutical compositions, and methods of using the same, are provided utilizing effective amounts of one or more flavones, flavonols, flavanones, isoflavanones and isoflavones to increase cell proliferation in various tissues and cell lines. As examples, the composition and methods of the present invention can be used to increase proliferation of fibroblast cells and, more particularly, in the treatment of wounds as well as strengthening of the skin.

Flexible, bioactive glass meshes and scaffolds made therefrom are provided. The meshes comprise interwoven bioactive glass fibers that can be coated with resorbable polymers. Meshes can also be woven from glass fibers and resorbable polymers. Scaffolds can be constructed by a plurality of meshes, which can have varying porosities to create porosity gradients in the scaffold. Methods of making scaffolds are provided which can comprise pulling bioactive glass fibers, winding the fibers, forming the fibers into bundles, coating the fibers with a resorbable polymer, and creating a biaxial weave with the bundles. Soft tissue engineering methods are also provided for creating scaffolds for incubating cells such as fibroblasts and chondroblasts. Meshes and scaffolds are suitable for tissue engineering, such as bone tissue engineering and cartilage tissue engineering.

The present invention provides defined serum-free cell culture media useful in culturing fibroblasts, especially articular chondrocytes, that avoids problems inherent in the use of serum-containing media. The defined media comprise platelet-derived growth factor (PDGF), and chemically defined lipids, or combinations of these compounds. In another aspect, the present invention also provides tissue culture methods that comprise incubating chondrocytes in the defined serum free media. The methods enhance attachment and proliferative expansion of chondrocytes seeded at low density while maintaining their redifferentiation potential.

The present methods and compositions are of use for treatment of conditions involving fibrosis, such as Peyronie's disease plaque, penile corporal fibrosis, penile veno-occlusive dysfunction, Dupuytren's disease nodules, vaginal fibrosis, clitoral fibrosis, female sexual arousal disorder, abnormal wound healing, keloid formation, general fibrosis of the kidney, bladder, prostate, skin, liver, lung, heart, intestines or any other localized or generalized fibrotic condition, vascular fibrosis, arterial intima hyperplasia, atherosclerosis, arteriosclerosis, restenosis, cardiac hypertrophy, hypertension or any condition characterized by excessive fibroblast or smooth muscle cell proliferation or deposition of collagen and extracellular matrix in the blood vessels and/or heart. In certain embodiments, the compositions may comprise a PDE-4 inhibitor, a PDE-5 inhibitor, a compound that elevates cGMP and/or PKG, a stimulator of guanylyl cyclase and/or PKG, a combination of a compound that elevates cGMP, PKG or NO with an antioxidant that decreases ROS, or a compound that increases MMP activity.

Immunogenic compositions and prophylactic or therapeutic vaccines for use in protecting and treating against human cytomegalovirus (CMV) are disclosed. Subunit vaccines comprising a human CMV protein complex comprising pUL128 or pUL130, and nucleic acid vaccines comprising at least one nucleic acid encoding a CMV protein complex comprising pUL128 or pUL130 are described. Also disclosed are therapeutic antibodies reactive against a CMV protein complex comprising pUL128 or pUL130, as well as methods for screening compounds that inhibit CMV infection of epithelial and endothelial cells, methods for immunizing a subject against CMV infection, methods for determining the capability of neutralizing antibodies to inhibit human CMV infection of cell types other than fibroblasts, and methods of diminishing an CMV infection.

The invention provides a composition for promoting regeneration of tissue which has degenerated in a subject as a result of a disease or disorder and a method of using the composition is provided. The composition comprises a biodegradable acellular matrix, and passaged autologous fibroblasts substantially free of immunogenic proteins, e.g., culture medium serum-derived proteins, integrated within the matrix. Also provided is an injectable composition comprising an acellular filler material (e.g., any type of collagen) and passaged autologous fibroblasts substantially free of immunogenic proteins, e.g., culture medium serum-derived proteins, for correcting defects in skin, such as wrinkles or scars, and for augmenting tissue in the subject, particularly facial tissue.

An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. One particularly important tissue sample preparation technique is the initial preparation of cohesive multicellular particulates of the tissue sample, rather than enzymatically dissociated cell suspensions or preparations, for initial tissue culture monolayer preparation. With respect to the culturing of malignant cells, for example, it is believed (without any intention of being bound by the theory) that by maintaining the malignant cells within a multicellular particulate of the originating tissue, growth of the malignant cells themselves is facilitated versus the overgrowth of fibroblasts or other cells which tends to occur when suspended tumor cells are grown in culture. Practical monolayers of cells may thus be formed to enable meaningful screening of a plurality of treatments and/or agents. Growth of cells is monitored to ascertain the time to initiate the assay and to determine the growth rate of the cultured cells; sequence and timing of drug addition is also monitored and optimized. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated.

The invention discloses a double-layer membranous tissue repair material and a preparation method thereof, wherein, a cell-free membranous biological derivative material is used as a surface layer, and a fibroblast is compounded in the interior of a biological support material to form a substrate, and then the surface layer and the substrate are combined in a chimeric way to form the double-layer membranous tissue repair material; a compact surface layer structure can effectively reduce the loss of water, electrolytes and protein from surface of wound, avoid the invading and the reproduction of bacteria to the impaired surface of wound as well as prevent the infection of the surface of wound, thus being beneficial to epitheliosis and epithelial growth; the substrate can directly repair the surface of wound, promote the ingrowth of cells around the surface of wound and the angiogenesis, induce the differentiation from stem cells to skin cells and quicken wound healing; compared with the existing products, the tissue repair material has the advantages of being capable of promoting the regeneration of skin, improving the elasticity, the flexibility and the mechanical abrasion resistance of skin after the surface of wound is healed, reducing hyperplasia of scar tissues, controlling the contracture, having excellent biocompatibility, increasing the success rate of transplant and improving the quality of healing; the invention has wide material resources and simple production method; the double-layer membranous tissue repair material prepared is applicable to the clinical treatment of skin defect caused by inflammation, ulcer, thermal burns, iatrogenicity and the like.

The invention provides an overexpression porcine co-stimulatory 4-1BB vector and application thereof. PCR (polymerase chain reaction) amplification is performed on a left homologous arm and a right homologous arm of an intron 1 of a rosa26 gene, a 4-1BB regulatory sequence and an OCT4 specific promoter; the left homologous arm, a 4-1BB expression cassette, LoxP locus-contained Cre and Neo expression cassettes, the right homologous arm and negative selection DTA diphtheria toxin are connected in sequence to obtain a 4-1BB homologous recombinant vector p4BOCNDR; the vector and a CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated) targeting vector of sgRNA (small guide ribonucleic acid) containing the intron 1 of the specific targeting porcine rosa26 gene are transferred together into a porcine fetus fibroblast; by taking a positive cell as a donor cell and an oocyte as a recipient cell, a cloned embryo is obtained through a somatic cell nuclear transfer technique; the cloned embryo is transplanted into a porcine uterus for fetation to obtain a transgenic pig integrating a 4-1BB gene at the fixed point of a first intron of the rosa26 gene and automatically deleting a marker gene.

Methods and compositions for the biological repair of cartilage using a hybrid construct combining both an inert structure and living core are described. The inert structure is intended to act not only as a delivery system to feed and grow a living, core component, but also as an inducer of cell differentiation. The inert structure comprises concentric internal and external and inflatable/expandable balloon-like bio-polymers. The living core comprises the cell-matrix construct comprised of HDFs, for example, seeded in a scaffold. The method comprises surgically removing a damaged cartilage from a patient and inserting the hybrid construct into the cavity generated after the foregoing surgical intervention. The balloons of the inert structure are successively inflated within the target area, such as a joint, for example. Also disclosed herein are methods for growing and differentiating human fibroblasts into chondrocyte-like cells via mechanical strain.

Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin(TM), interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions that produce abnormal growth, including treatment of malignant and benign neoplasias, vascular malformations (hemangiomas), inflammatory conditions, keloid formation, abdominal or plural adhesions, endometriosis, congenital or endocrine abnormalities, and other conditions that can produce abnormal growth such as infection. Efficacy of treatment with the therapeutic biologicals is detected by determining specific criteria, for example, cessation of cell proliferation, regression of abnormal tissue, or cell death, or expression of genes or proteins reflecting the above.

The invention discloses single guide ribonucleic acid (sgRNA) capable of effectively editing a pig ROSA26 gene, and application of the sgRNA. Based on the sgRNA capable of specifically identifying the pig ROSA26 gene in a pig genome, a cell line of enhanced green fluorescent protein (EGFP) site-specific integrated porcine fetal fibroblasts is successfully established by using a CRISPR/Cas9-mediated gene knock-in technique; the results show that the cell line can stably and efficiently express an EGFP gene; furthermore, in the preparation process of the cell line, exogenous promoter genes and positive and negative screening marker genes are not introduced into the cell line. Therefore, the sgRNA greatly improves the safety of transgenic pigs, and has important significance for eliminating the biological and food potential safety hazards of agricultural products of the transgenic pigs.

A biomedical material for transplant to a subject is provided according to embodiments of the present invention which includes an isolated donor tissue enzyme-treated to reduce the amount of proteoglycans in the donor tissue compared to untreated tissue. Isolated cells are optionally added to the enzyme-treated donor tissue, including leukocytes, particularly monocytes; macrophages; platelets; cells derived from an intervertebral disc such as chondrocyte-like nucleus pulposus cells; fibrocytes; fibroblasts; mesenchymal stem cells; mesenchymal precursor cells; chondrocytes; or a combination of any of these. The isolated donor tissue is articular cartilage or an intervertebral disc tissue such as nucleus pulposus tissue and/or annulus fibrosis tissue enzyme-treated to remove proteoglycans normally present in these tissues. A biomedical material of the present invention is administered to a subject to treat a disorder or injury, such as a disorder or injury to connective tissue.

The present invention relates to a population of blood borne mammalian cells that express a unique profile of surface markers that includes certain markers typical of connective tissue fibroblasts, and are referred to herein as "blood-borne mesenchymal cells." In particular, it relates to the isolation, characterization and uses of such blood-borne mesenchymal cells. The cells of the present invention can be distinguished from peripheral blood leukocytes by their distinct size, morphology, cell surface phenotype and biologic activities, and are likewise distinguishable from connective tissue fibroblasts by other surface phenotypic markers. These cells proliferate in culture, and in vivo, as demonstrated in animal models, are capable of migrating into wound sites from the blood. Therefore, such blood-borne mesenchymal cells may have a wide range of applications, including, but not limited to, the promotion of wound healing, tissue remodeling, and for gene therapy.

To control cardiac arrhythmias, various conduction-modifying agents include biopolymers, fibroblasts, neurotoxins, and growth factors are introduced either epicardially or endocardially to the fat pads in proximity to the ganglia therein. Any desired technique may be used for injection, including injection from a catheter inserted percutaneously, or direct injection through the epicardial during open heart surgery. Preferably the patient's heart is beating throughout the Injection.

The present invention provides a novel method to isolate and expand pure progenitor/stem cells from a primary tissue explant, which produces a population enriched in multipotent functional progenitor/stem cells free of contaminating fibroblasts and other cell types. Cardiac progenitor/stem cells isolated by this method maintain their self-renewal and clonogenic character in vitro and differentiate into normal cells in myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells, after transplantation into ischemic hearts. The present invention also includes substantially pure populations of multipotent progenitor/stem cells, e.g., cardiac progenitor/stem cells, and their use to treat and prevent diseases and injuries, including those resulting from myocardial infarction.

Agonists of the adenosine A2 receptor promote the migration of endothelial cells, fibroblasts and epithelial cells. Thus, methods and pharmaceutical compositions useful for treating wounds and promoting wound healing comprise agents which cause stimulation of the adenosine A2 receptor, preferably receptor agonists and adenosine uptake blockers. Preferred agonists include 2-phenylaminoadenosine, 2-para-2-carboxyethylphenyl-amino-5'N-ethylcarboxamidoadenosine, 5'N-ethylcarbox-amidoadenosine, 5'N-cyclo-propyladenosine, 5'N-methylcarboxamidoadenosine and PD-125944. Preferred uptake blockers include dipyridamole, nitrobenzylthio-inosine, dilazep and R75231.

The present invention relates to a population of blood borne mammalian cells that express a unique profile of surface markers that includes certain markers typical of connective tissue fibroblasts, and are referred to herein as "blood-borne mesenchymal cells." In particular, it relates to the isolation, characterization and uses of such blood-borne mesenchymal cells. The cells of the present invention can be distinguished from peripheral blood leukocytes by their distinct size, morphology, cell surface phenotype and biologic activities, and are likewise distinguishable from connective tissue fibroblasts by other surface phenotypic markers. These cells proliferate in culture, and in vivo, as demonstrated in animal models, are capable of migrating into wound sites from the blood. Therefore, such blood-borne mesenchymal cells may have a wide range of applications, including, but not limited to, the promotion of wound healing, tissue remodeling, and for gene therapy.