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A fibroblast is a type of
biological cell The cell (from Latin ''cella'', meaning "small room") is the basic structural, functional, and biological unit of all known organisms. Cells are the smallest units of life, and hence are often referred to as the "building blocks of life". The s ...
that synthesizes the
extracellular matrix In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, ...
and
collagen Collagen () is the main structural in the found in the body's various s. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole-body protein content. Collagen consists of ...

collagen
, produces the structural framework ( stroma) for animal tissues, and plays a critical role in
wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis The epidermis is the outermost of the three layers that comprise the skin Skin is the layer of ...
. Fibroblasts are the most common cells of
connective tissue Connective tissue is one of the many basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consum ...
in animals.


Structure

Fibroblasts have a branched
cytoplasm In , the cytoplasm is all of the material within a , enclosed by the , except for the . The material inside the nucleus and contained within the is termed the . The main components of the cytoplasm are (a gel-like substance), the s (the cell' ...
surrounding an elliptical, speckled
nucleus ''Nucleus'' (plural nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA ...

nucleus
having two or more
nucleoli The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis. Nucleoli also participate in the formation of signal recognition particles and play a role ...
. Active fibroblasts can be recognized by their abundant
rough endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
. Inactive fibroblasts (called fibrocytes) are smaller, spindle-shaped, and have a reduced amount of rough endoplasmic reticulum. Although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters. Unlike the
epithelial Epithelium is one of the four basic types of animal Tissue (biology), tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed Cell (biology), cells with little Extr ...
cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a
basal lamina The basal lamina is a layer of extracellular matrix In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular ...

basal lamina
on one side, although they may contribute to basal lamina components in some situations (e.g. subepithelial
myofibroblasts A myofibroblast is a cell that is in between a fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix In biology Biology is the natural science that studies life and living organisms, including thei ...
in
intestine The gastrointestinal tract, (GI tract, GIT, digestive tract, digestion tract, alimentary canal) is the tract from the mouth to the anus which includes all the organs of the digestive system The human digestive system consists of the human ...

intestine
may secrete the α-2 chain-carrying component of the
laminin Laminins are high-molecular weight A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically Electricity is the set of physical phenomena assoc ...
, which is absent only in regions of follicle-associated epithelia which lack the myofibroblast lining). Fibroblasts can also migrate slowly over substratum as individual cells, again in contrast to epithelial cells. While epithelial cells form the lining of body structures, it is fibroblasts and related connective tissues which sculpt the "bulk" of an organism. The life span of a fibroblast, as measured in chick embryos, is 57 ± 3 days.


Relationship with fibrocytes

Fibroblasts and
fibrocyte A fibrocyte is an inactive mesenchymal cell, that is, a cell showing minimal cytoplasm, limited amounts of rough endoplasmic reticulum and lacks biochemical evidence of protein synthesis Protein biosynthesis (or protein synthesis) is a core biol ...
s are two states of the same cells, the former being the activated state, the latter the less active state, concerned with maintenance and tissue metabolism. Currently, there is a tendency to call both forms fibroblasts. The suffix "-blast" is used in cellular biology to denote a
stem cell In multicellular organisms Multicellular organisms are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies the Life#Biology, properties o ...
or a cell in an activated state of
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life Life is a characteristic that distinguishes physical entities that have biological processes, such as Cell signaling, signaling and self-sustaining ...

metabolism
. Fibroblasts are morphologically heterogeneous with diverse appearances depending on their location and activity. Though morphologically inconspicuous, ectopically transplanted fibroblasts can often retain positional memory of the location and tissue context where they had previously resided, at least over a few generations. This remarkable behavior may lead to discomfort in the rare event that they stagnate there excessively.


Development

The main function of fibroblasts is to maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix. Fibroblasts secrete the precursors of all the components of the extracellular matrix, primarily the
ground substanceGround substance is an amorphous gel-like substance in the extracellular space that contains all components of the extracellular matrix In biology Biology is the natural science that studies life and living organisms, including their anatomy, ...
and a variety of
fibers Fiber or fibre (from la, fibra, links=no) is a natural Nature, in the broadest sense, is the natural, physical, material world or universe The universe ( la, universus) is all of space and time and their contents, including ...
. The composition of the extracellular matrix determines the physical properties of connective tissues. Like other cells of connective tissue, fibroblasts are derived from primitive
mesenchyme Mesenchyme () is a type of loosely organised animal embryonic ''Embryonic'' is the twelfth studio album by experimental rock band the Flaming Lips released on October 13, 2009, on Warner Bros. Records, Warner Bros. The band's first double album, ...
. Thus they express the intermediate filament protein
vimentin Vimentin is a structural protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, incl ...

vimentin
, a feature used as a marker to distinguish their
mesodermal In all bilaterian animals, the mesoderm is one of the three primary germ layer A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrate Vertebrates () comprise all species of ani ...
origin. However, this test is not specific as epithelial cells cultured in vitro on adherent substratum may also express vimentin after some time. In certain situations, epithelial cells can give rise to fibroblasts, a process called
epithelial-mesenchymal transition
epithelial-mesenchymal transition
(EMT). Conversely, fibroblasts in some situations may give rise to epithelia by undergoing a mesenchymal to epithelial transition (MET) and organizing into a condensed, polarized, laterally connected true epithelial sheet. This process is seen in many developmental situations (e.g.
nephron The nephron is the microscopic structural and functional unit of the kidney The kidneys are two reddish-brown bean-shaped organ (anatomy), organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in ...

nephron
and notocord development), as well as in wound healing and tumorigenesis.


Function

Fibroblasts make
collagen fibre
collagen fibre
s,
glycosaminoglycan . For polysaccharide nomenclature see oligosaccharide nomenclature, here. R1, R2, R3 may have different values. Glycosaminoglycans (GAGs) or mucopolysaccharides are long linear polysaccharides consisting of repeating disaccharide units (i.e. two-su ...
s, reticular and
elastic fibers Elastic fibers (or yellow fibers) are an essential component of the extracellular matrix composed of bundles of proteins (elastin) which are produced by a number of different cell types including fibroblasts, endothelial, smooth muscle, and airw ...
. Growing individuals' fibroblasts are dividing and are synthesizing
ground substanceGround substance is an amorphous gel-like substance in the extracellular space that contains all components of the extracellular matrix In biology Biology is the natural science that studies life and living organisms, including their anatomy, ...
. Tissue damage stimulates fibrocytes and induces the production of fibroblasts.


Inflammation

Besides their commonly known role as structural components, fibroblasts play a critical role in an immune response to a tissue injury. They are early players in initiating inflammation in the presence of invading microorganisms. They induce chemokine synthesis through the presentation of receptors on their surface. Immune cells then respond and initiate a cascade of events to clear the invasive microorganisms. Receptors on the surface of fibroblasts also allow regulation of
hematopoietic cells
hematopoietic cells
and provide a pathway for immune cells to regulate fibroblasts.


Tumour mediation

Fibroblasts, like the tumor-associated host fibroblasts (TAF), play a crucial role in immune regulation through TAF-derived extracellular matrix (ECM) components and modulators. TAF are known to be significant in the inflammatory response as well as immune suppression in tumors. TAF-derived ECM components cause alterations in the ECM composition and initiate the ECM remodeling. The ECM remodeling is described as changes in the ECM as a result of enzyme activity which can lead to degradation of the ECM. Immune regulation of tumors is largely determined by the ECM remodeling because the ECM is responsible for regulating a variety of functions, such as proliferation, differentiation, and morphogenesis of vital organs. In many tumor types, especially those related to the epithelial cells, ECM remodeling is common. Examples of TAF-derived ECM components include Tenascin and Thrombospondin-1 (TSP-1), which can be found in sites of chronic inflammation and carcinomas, respectively. Immune regulation of tumors can also occur through the TAF-derived modulators. Although these modulators may sound similar to the TAF-derived ECM components, they differ in the sense that they are responsible for the variation and turnover of the ECM. Cleaved ECM molecules can play a critical role in immune regulation. Proteases like matrix metalloproteineases (MMPs) and the uPA system are known to cleave the ECM. These proteases are derived from fibroblasts.


Secondary actions

Mouse embryonic fibroblast Mouse Embryonic Fibroblasts (MEFs) are a type of fibroblast prepared from mouse embryo. MEFs show a spindle shape when cultured ''in vitro'', a typical feature of fibroblasts. The MEF is a limited cell line. After several transmission, MEFs will se ...
s (MEFs) are often used as "feeder cells" in human embryonic
stem cell In multicellular organisms Multicellular organisms are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies the Life#Biology, properties o ...
research. However, many researchers are gradually phasing out MEFs in favor of culture media with precisely defined ingredients of exclusively human derivation. Further, the difficulty of exclusively using human derivation for media supplements is most often solved by use of "defined media" where the supplements are synthetic and achieve the primary goal of eliminating the chance of contamination from derivative sources. In view of the clinical application of stem cell derived tissues, the use of human fibroblast as feeders has been studied. Whereas the fibroblasts are usually used to maintain pluripotency of the stem cells, they can also be used to facilitate development of the stem cells into specific type of cells such as cardiomyocytes.


Host immune response

Fibroblasts from different anatomical sites in the body express many genes that code for and proteins. These mediators of immune response enable the
cellular communication A mobile phone, cellular phone, cell phone, cellphone, handphone, or hand phone, sometimes shortened to simply mobile, cell or just phone, is a portable telephone that can make and receive telephone call, calls over a radio frequency link wh ...
with hematopoietic immune cells. The immune activity of non-hematopoietic cells, such as fibroblasts, is referred to as “structural immunity”. In order to facilitate a fast response to immunological challenges, fibroblasts encode crucial aspects of the structural cell immune response in the
epigenomeAn epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome c ...

epigenome
.


See also

*
Fibrocartilage callus Comminuted midshaft humerus fracture with callus formation. A fibrocartilage callus is a temporary formation of fibroblasts and chondroblasts which forms at the area of a bone fracture as the bone attempts to healing, heal itself. The cells even ...


References


External links

* * {{Authority control Non-terminally differentiated (blast) cells Connective tissue cells GAG secreting cells