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Matrigel is the trade name for the solubilized basement membrane matrix secreted by Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells produced by Corning Life Sciences. Matrigel resembles the laminin/collagen IV-rich basement membrane extracellular environment found in many tissues and is used by cell biologists as a substrate (basement membrane matrix) for culturing cells. [1] [2]
A common laboratory procedure is to dispense small volumes of chilled (4 °C) liquid Matrigel onto plastic tissue culture labware. When incubated at 37 °C (body temperature) the Matrigel proteins polymerize (solidify) producing a recombinant basement membrane that covers the labware's surface.
Cells cultured on Matrigel demonstrate complex cellular behavior that is otherwise difficult to observe under laboratory conditions. For example, endothelial cells create intricate spiderweb-like networks on Matrigel-coated surfaces but not on plastic surfaces. [3] Such networks are highly suggestive of the microvascular capillary systems that suffuse living tissues with blood. Hence, Matrigel allows them to observe the process by which endothelial cells construct such networks that are of great research interest.
In some instances researchers may prefer to use greater volumes of Matrigel to produce thick three-dimensional gels. Thick gels induce cells to migrate from the gel's surface to its interior. This migratory behavior is studied by researchers as a model of tumor cell metastasis.[ citation needed ]
Pharmaceutical scientists use Matrigel to screen drug molecules. A typical experiment consists of adding a test molecule to Matrigel and observing cellular behavior. Test molecules that promote endothelial cell network formation are candidates for tissue regeneration therapies whereas test molecules that inhibit endothelial cell network formation are candidates for anti-cancer therapies. Likewise, test molecules that inhibit tumor cell migration may also have potential as anti-cancer drugs. Matrigel is also commonly used to prepare human tumor xenografts in rodents as part of a cancer drug discovery program. [4] Matrigel is mixed with immortalized human cancer cells and the mixture is injected subcutaneously in immunodeficient mice. A human tumor usually forms in two to four weeks. This model system allows a researcher to test an anti-cancer compound in a surrogate host.
The ability of Matrigel to stimulate complex cell behavior is a consequence of its heterogeneous composition. The chief components of Matrigel are structural proteins such as laminin, nidogen, collagen and heparan sulfate proteoglycans which present cultured cells with the adhesive peptide sequences that they would encounter in their natural environment. [1] Also present are growth factors like TGF-beta and EGF that prevent differentiation and promote proliferation of many cell types. A growth-factor-reduced Matrigel is also available. Matrigel contains other proteins in small amounts and its exact composition can vary from lot to lot. For this reason, Matrigel may not be appropriate for experiments that require precise knowledge of all proteins and concentrations.
Matrigel is also used as an attachment substrate in embryonic stem cell culture. [5] When embryonic stem cells are grown in the absence of feeder cells, extracellular matrix components are needed to maintain the pluripotent, undifferentiated state (self-renewal). One of these matrices that can be used is diluted Matrigel. When used undiluted, Matrigel promotes stem cell growth and differentiation.
Morphogenesis is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of tissue growth and patterning of cellular differentiation.
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals.
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.
Haptotaxis is the directional motility or outgrowth of cells, e.g. in the case of axonal outgrowth, usually up a gradient of cellular adhesion sites or substrate-bound chemoattractants. These gradients are naturally present in the extracellular matrix (ECM) of the body during processes such as angiogenesis or artificially present in biomaterials where gradients are established by altering the concentration of adhesion sites on a polymer substrate.
The basement membrane, also known as base membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium and endothelium, and the underlying connective tissue.
Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina, the protein network foundation for most cells and organs. The laminins are an important and biologically active part of the basal lamina, influencing cell differentiation, migration, and adhesion.
Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the HSPG2 gene. The HSPG2 gene codes for a 4,391 amino acid protein with a molecular weight of 468,829. It is one of the largest known proteins.
Intravasation is the invasion of cancer cells through the basement membrane into a blood or lymphatic vessel. Intravasation is one of several carcinogenic events that initiate the escape of cancerous cells from their primary sites. Other mechanisms include invasion through basement membranes, extravasation, and colonization of distant metastatic sites. Cancer cell chemotaxis also relies on this migratory behavior to arrive at a secondary destination designated for cancer cell colonization.
Cardiomyoplasty is a surgical procedure in which healthy muscle from another part of the body is wrapped around the heart to provide support for the failing heart. Most often the latissimus dorsi muscle is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged myocardium to be treated in other ways, such as remodeling by cellular therapies.
Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the SPARC gene.
Stem-cell niche refers to a microenvironment, within the specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate. The word 'niche' can be in reference to the in vivo or in vitro stem-cell microenvironment. During embryonic development, various niche factors act on embryonic stem cells to alter gene expression, and induce their proliferation or differentiation for the development of the fetus. Within the human body, stem-cell niches maintain adult stem cells in a quiescent state, but after tissue injury, the surrounding micro-environment actively signals to stem cells to promote either self-renewal or differentiation to form new tissues. Several factors are important to regulate stem-cell characteristics within the niche: cell–cell interactions between stem cells, as well as interactions between stem cells and neighbouring differentiated cells, interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, growth factors, cytokines, and the physicochemical nature of the environment including the pH, ionic strength and metabolites, like ATP, are also important. The stem cells and niche may induce each other during development and reciprocally signal to maintain each other during adulthood.
Microvesicles are a type of extracellular vesicle (EV) that are released from the cell membrane. In multicellular organisms, microvesicles and other EVs are found both in tissues and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs or as large as 1000 nm. They are considered to be larger, on average, than intracellularly-generated EVs known as exosomes. Microvesicles play a role in intercellular communication and can transport molecules such as mRNA, miRNA, and proteins between cells.
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2.
Laminin subunit alpha-4 is a protein that in humans is encoded by the LAMA4 gene.
Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.
Laminin–111 is a protein of the type known as laminin isoforms. It was among the first of the laminin isoforms to be discovered. The "111" identifies the isoform's chain composition of α1β1γ1. This protein plays an important role in embryonic development. Injections of this substance are used in treatment for Duchenne muscular dystrophy, and its cellular action may potentially become a focus of study in cancer research.
In biology, fractones are structures consisting primarily of laminin and heparan sulfate proteoglycan (HSPG) first discovered in the extracellular matrix niche of the subventricular zone of the lateral ventricle (SVZa) in the mouse brain. Recent research has suggested its importance in adult neurogenesis, gliogenesis, and angiogenesis.
Cultrex Basement Membrane Extract (BME) is the trade name for a extracellular protein mixture secreted by Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells and manufactured into a hydrogel by R&D Systems, a brand of Bio-Techne. Similar to Matrigel, this hydrogel is a natural extracellular matrix that mimics the complex extracellular environment within complex tissues. It is used as a general cell culture substrate across a wide variety of research applications.
Karl Tryggvason is an Icelandic medical researcher.
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