581 results about "Stromal cell" patented technology

Novel products comprising conditioned cell culture medium compositions and methods of use are described. The conditioned cell medium compositions of the invention may be comprised of any known defined or undefined medium and may be conditioned using any eukaryotic cell type. The medium may be conditioned by stromal cells, parenchymal cells, mesenchymal stem cells, liver reserve cells, neural stem cells, pancreatic stem cells and / or embryonic stem cells. Additionally, the cells may be genetically modified. A three-dimensional tissue construct is preferred. Once the cell medium of the invention is conditioned, it may be used in any state. Physical embodiments of the conditioned medium include, but are not limited to, liquid or solid, frozen, lyophilized or dried into a powder. Additionally, the medium is formulated with a pharmaceutically acceptable carrier as a vehicle for internal administration, applied directly to a food item or product, formulated with a salve or ointment for topical applications, or, for example, made into or added to surgical glue to accelerate healing of sutures following invasive procedures. Also, the medium may be further processed to concentrate or reduce one or more factors or components contained within the medium.

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.

Methods and compositions for directing adipose-derived stromal cells cultivated in vitro to differentiate into cells of the chondrocyte lineage are disclosed. The invention further provides a variety of chondroinductive agents which can be used singly or in combination with other nutrient components to induce chondrogenesis in adipose-derived stromal cells either in cultivating monolayers or in a biocompatible lattice or matrix in a three-dimensional configuration. Use of the differentiated chondrocytes for the therapeutic treatment of a number of human conditions and diseases including repair of cartilage in vivo is disclosed.

The invention relates to methods and compositions for the differentiation of stromal cells from adipose tissue into hematopoietic supporting stromal cells and myocytes of both the skeletal and smooth muscle type. The cells produced by the methods are useful in providing a source of fully differentiated and functional cells for research, transplantation and development of tissue engineering products for the treatment of human diseases and traumatic tissue injury repair.

The invention is in the area of pleuripotent stem cells generated from adipose tissue-derived stromal cells and uses thereof. In particular, the invention includes isolated adipose tissue derived stromal cells that have been induced to express at least one phenotypic characteristic of a neuronal, astroglial, hematopoietic progenitor, or hepatic cell. The invention also includes an isolated adipocyte tissue-derived stromal cell that has been dedifferentiated such that there is an absence of adipocyte phenotypic markers.

Methods and compositions for directing adipose-derived stromal cells cultivated in vitro to differentiate into cells of the chondrocyte lineage are disclosed. The invention further provides a variety of chondroinductive agents which can be used singly or in combination with other nutrient components to induce chondrogenesis in adipose-derived stromal cells either in cultivating monolayers or in a biocompatible lattice or matrix in a three-dimensional configuration. Use of the differentiated chondrocytes for the therapeutic treatment of a number of human conditions and diseases including repair of cartilage in vivo is disclosed.

A method of expanding / maintaining undifferentiated hemopoietic stem cells or progenitor cells by obtaining undifferentiated hemopoietic stem cells or progenitor cells; and either seeding the undifferentiated hemopoietic stem cells or progenitor cells into a stationary phase plug-flow bioreactor in which a three-dimensional stromal cell culture has been pre-established on a substrate in the form of a sheet, the substrate including a non-woven fibrous matrix forming a physiologically acceptable three-dimensional network of fibers, thereby expanding / maintaining undifferentiated hemopoietic stem cells or progenitor cells, or culturing the undifferentiated hemopoietic stem cells or progenitor cells in conditioned medium obtained from such a reactor.

Clinical information, molecular information and / or computer-generated morphometric information is used in a predictive model for predicting the occurrence of a medical condition. In an embodiment, a model predicts whether a patient is likely to have a favorable pathological stage of prostate cancer, where the model is based on features including one or more (e.g., all) of preoperative PSA, Gleason Score, a measurement of expression of androgen receptor (AR) in epithelial and stromal nuclei and / or a measurement of expression of Ki67-positive epithelial nuclei, a morphometric measurement of a ratio of area of epithelial nuclei outside gland units to area of epithelial nuclei within gland units, and a morphometric measurement of area of epithelial nuclei distributed away from gland units. In some embodiments, quantitative measurements of protein expression in cell lines are utilized to objectively assess assay (e.g., multiplex immunofluorescence (IF)) performance and / or to normalize features for use within a predictive model.

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.

The present invention generally relates to use of adult Adipose-derived stromal cells (ASC) and genetically engineered ASC for the treatment of cancer. In particular, the present invention generally relates, in part to a method for treating a subject with cancer comprising administering to the subject a composition comprising engineered ASCs which have been modified to express a gene encoding at least one anti-cancer agent. In some embodiments, an anti-cancer agent is a pro-apoptotic agent. In some embodiments an anti-cancer agent is an agent which inhibits the expression of an oncogene.

The invention provides cells, compositions and methods based on the differentiation of adipose tissue-derived stromal cells into a cell expressing at least one genotypic or phenotypic characteristic of a pancreas cell. The cells produced in the method are useful in providing a source of differentiated and functional cells for research, implantation, transplantation and development of tissue engineered products for the treatment of diseases of the pancreas and pancreatic tissue repair.

Provided herein are novel methods and compositions utilizing adipose tissue-derived stromal stem cells for treating fistulae.

The invention provides cells, compositions and methods based on the use of stromal cells to support the proliferation of undifferentiated embryonic or adult stem cells in vitro. The stem cells produced in the method are useful in providing a source of uncommitted or differentiated and functional cells for research, transplantation and development of tissue engineered products for the treatment of human diseases and traumatic tissue injury repair in any tissue or organ site within the body.

Novel products comprising conditioned cell culture medium compositions and methods of use are described. The conditioned cell medium compositions of the invention may be comprised of any known defined or undefined medium and may be conditioned using any eukaryotic cell type. The medium may be conditioned by stromal cells, parenchymal cells, mesenchymal stem cells, liver reserve cells, neural stem cells, pancreatic stem cells and / or embryonic stem cells. Additionally, the cells may be genetically modified. A three-dimensional tissue construct is preferred. Once the cell medium of the invention is conditioned, it may be used in any state. Physical embodiments of the conditioned medium include, but are not limited to, liquid or solid, frozen, lyophilized or dried into a powder. Additionally, the medium is formulated with a pharmaceutically acceptable carrier as a vehicle for internal administration, applied directly to a food item or product, formulated with a salve or ointment for topical applications, or, for example, made into or added to surgical glue to accelerate healing of sutures following invasive procedures. Also, the medium may be further processed to concentrate or reduce one or more factors or components contained within the medium.

The present invention provides methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells. In particular, the present invention includes a debulking step that uses a microfabricated filters for filtering fluid samples and the enriched rare cells can be used in a downstream process such as identifies, characterizes or even grown in culture or used in other ways. The invention also include a method of determining the aggressiveness of the tumor or of the number or proportion of cancer cells in the enriched sample by detecting the presence or amount of telomerase activity or telomerase nucleic acid or telomerase expression after enrichment of rare cells. This invention further provides an efficient and rapid method to specifically remove red blood cells as well as white blood cells from a biological sample containing at least one of each of red blood cells and white blood cells, resulting in the enrichment of rare target cells including circulating tumor cells (CTC), stromal cells, mesenchymal cells, endothelial cells, fetal cells, stem cells, non-hematopoietic cells etc from a blood sample. The method is based upon combination of immuno-microparticles (antibody coated microparticles) and density-based separation. The final enriched target cells can be subjected to a variety of analysis and manipulations, such as flowcytometry, PCR, immunofluorescence, immunocytochemistry, image analysis, enzymatic assays, gene expression profiling analysis, efficacy tests of therapeutics, culturing of enriched rare cells, and therapeutic use of enriched rare cells. In addition, depleted plasma protein and white blood cells can be optionally recovered, and subjected to other analysis such as inflammation studies, gene expression profiling, etc.

A method for preparing a tissue culture insert that is used for constructing a transplantable graft of an engineered tissue equivalent comprising living main functional cells, stromal cells and tissue matrix on / in a biological supporting membrane for treatment of body tissue defects.

The present invention is differentiated adipose tissue-derived stromal cells that exhibit the improved properties of increased extracellular matrix proteins and / or a lower amount of lipid than a mature isolated adipocyte. Methods for the expansion and differentiation of these cells are also provided. The cells of the invention are used for the treatment, repair, correction and / or regeneration of soft tissue cosmetic defects.

Three-dimensional tissue-like organization of cells by high cell-seeding-density culture termed as macromass culture is described. By macromass culture, cells can be made to organize themselves into a tissue-like form without the aid of a scaffold and three-dimensional macroscopic tissue-like constructs can be made wholly from cells. Tissue-like organization and macroscopic tissue-like constructs can be generated from fibroblastic cells of mesenchymal origin (at least), which can be either differentiated cells or multipotent adult stem cells. In this work, tissue-like organization and macroscopic tissue-like constructs have been generated from dermal fibroblasts, adipose stromal cells-derived osteogenic cells, chondrocytes, and from osteoblasts. The factor causing macroscopic tissue formation is large scale culture at high cell seeding density per unit area or three-dimensional space, that is, macromass culture done on a large scale. No scaffold or extraneous matrix is used for tissue generation, the tissues are of completely cellular origin. No other agents (except high cell-seeding-density) that aid in tissue formation such as tissue-inducing chemicals, tissue-inducing growth factors, substratum with special properties, rotational culture, etc, are employed for tissue formation. These tissue-like masses have the potential for use as tissue replacements in the human body. Tissue-like organization by high cell-seeding-density macromass culture can also be generated at the microscopic level.

Disclosed are engineered, living, three-dimensional connective tissue constructs comprising connective tissue cells. In some embodiments, the connective tissue cells are derived from multi-potent cells such as mesenchymal stem / stromal cells. In some embodiments, the cells are cohered to one another. In some embodiments, the multi-potent cells have been exposed to one or more differentiation signals to provide a living, three-dimensional connective tissue construct. In some embodiments, the constructs are substantially free of pre-formed scaffold at the time of use. Also disclosed are implants for engraftment, arrays of connective tissue constructs for in vitro experimentation, as well as methods of making the same.

The present invention relates to methods of using granulocyte colony stimulating factor (G-CSF) polypeptide, alone and in conjunction with stromal cell derived factor (SDF-1) polypeptide, to increase the mobilization of c-Kit+ stem cells in the blood, bone marrow, tissue, heart or other organs for the subsequent production of embryoid body-like cell clusters. These embryoid body-like cell clusters can be used for cell replacement therapy, for the treatment of cardiac myopathy and other diseases and disorders, and for screening agents that drive or inhibit differentiation and proliferation.

The present invention relates to a treatment of neural injury and neurodegenerative diseases. Also included in the present invention is the use of adipose tissue derived stromal cells for the treatment of neural injury (stroke, traumatic brain injury, spinal cord injury) and neurodegeneration (i.e. Parkinson's disease).

The present disclosure relates generally to processes, devices and systems for separating and concentrating stem and stromal cells from adipose tissue using a combination of mechanical disruption and filtration-centrifugation to obtain a highly enriched population of stem cells.

The invention discloses acellular cornea or acellular corneal stroma, a preparation method and application thereof. The method comprises the following steps of: (1) obtaining fresh animal full-thickness cornea or corneal stroma; (2) removing corneal epithelium, corneal endothelium and stroma cells, namely 1, soaking the full-thickness cornea or the corneal stroma in pure water at room temperature; 2, placing the soaked full-thickness cornea or corneal stroma into enzyme solution, digesting with oscillating, and washing with balanced salt solution with oscillating; and 3, repeating freeze-thaw processes of the full-thickness cornea or the corneal stroma for 4 to 8 times and washing with balanced salt solution with oscillating to obtain the acellular cornea or the acellular corneal stroma; (3) dehydrating; and (4) sterilizing and storing. In the method, the decellularization processing time of the cornea is short; the influence on the structure and the physiological property of the cornea is small; and the processed cornea has very low immunogenicity which is similar to the property of natural cornea. The acellular cornea or the acellular corneal stroma can be applied to artificial cornea construction of tissue engineering and also can serve as a medical material applied to corneal transplantation and refraction surgery.

Use of the antimicrobial cathelicidin peptide ll-37, N-terminal fragments of LL-37 or extended sequences of LL-37 having 1-3 amino acids in the C-terminal end, for stimulating proliferation of epithalial and stromal cells and thereby healing of wounds, such as chronic ulcers. The cytotoxic effect of LL-37 may be reduced by including a bilayer-forming polar lipid, especially a digalactosyldiacylglycerol, in pharmaceutical compositions and growth media comprising LL-37.

Provided is a method of culturing a successor cell from a precursor cell comprising co-culturing a precursor cell such as, without limitation, a human embryonic stem cell or a neuronal stem cell with an adult mesenchymal stem cell. In one embodiment, the adult mesenchymal stem cell is derived from adipose tissue. Also provided is a composition comprising mesenchymal stem cells in a growth matrix biologically-compatible with the cells. In another embodiment, a method of regenerating tissue is provided comprising introducing into a patient a cell growth niche comprising either or both of mesenchymal stem cells and neuronal stem cell or successor cell in a growth matrix biologically-compatible with the cells. In another embodiment, a method of regenerating tissue is provided comprising introducing into a patient a cell growth niche comprising matrix, cells and slow release polymer beads containing growth factors.

The present invention is directed stromal cell derived factor-1 peptides that have been mutated to make them resistant to digestion by the proteases dipeptidyl peptidase IV (DPPIV) and matrix metalloproteinase-2 (MMP-2) but which maintain the ability of native SDF-1 to attract T cells. The mutants may be attached to membranes formed by self-assembling peptides and then implanted at sites of tissue damage to help promote repair.

A method of preparing a stromal cell conditioned medium useful in expanding undifferentiated hemopoietic stem cells to increase the number of the hemopoietic stem cells is provided. The method comprising: (a) establishing a stromal cell culture in a stationary phase plug-flow bioreactor under continuous flow on a substrate in the form of a sheet, the substrate including a non-woven fibrous matrix forming a physiologically acceptable three-dimensional network of fibers, thereby expanding undifferentiated hemopoietic stem cells; and (b) when a desired stromal cell density has been achieved, collecting medium from the stationary phase plug-flow bioreactor, thereby obtaining the stromal cell conditioned medium useful in expanding the undifferentiated hemopoietic stem cells.

Adipose tissue-derived stromal cells induced to form multicellular aggregates can be formed reliably and consistently, they can be maintained for prolonged periods in adherent or suspension culture, and they are able to survive, grow, and / or differentiate in serum-free media conditions. The present invention provides compositions and methods for the use of such aggregates in tissue repair. This culture platform provides a controlled and defined system in which to study and standardize adult stem cell biology, and begets an instinctive “modular” approach to the predictable replacement and regeneration of adipose tissue.

A method is provided for facilitating treatment of a patient, including stressing a portion of the patient to an extent sufficient to induce homing of progenitor cells to the portion of the patient. A method is additionally provided for use with tissue of a patient, including evaluating an indication of a level of stromal cell-derived factor-1 (SDF-1) in the tissue, and determining an indication of a number of stem cells in the tissue responsive to the indication of the level of SDF-1. A method is yet additionally provided for use with tissue of a patient, including evaluating an indication of a level of SDF-1 in the tissue, and determining an indication of a level of stress of a portion of the patient, responsive to the indication of the level of SDF-1. Other embodiments are also described.