| Fibroblast |
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NIH/3T3 Fibroblasts in cell culture
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| Details |
| Identifiers |
| Latin |
fibroblastus |
| Code |
TH H2.00.03.0.01002 |
| Anatomical terminology
[edit on Wikidata]
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A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen,[1] 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.
Contents
- 1 Background information
- 2 Embryologic origin
- 3 Structure and function
- 3.1 Immune System Functions
- 3.1.1 Initiation of Inflammation
- 3.1.2 Mediation of Tumors
- 4 Secondary actions
- 5 See also
- 6 References
- 7 External links
Background information
Fibroblasts and fibrocytes 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 or a cell in an activated state of 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[clarification needed] in the rare event that they stagnate there excessively.
Embryologic origin
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 substance and a variety of fibers. 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. Thus they express the intermediate filament protein vimentin, a feature used as a marker to distinguish their mesodermal origin.[2] 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 (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 and notocord development), as well as in wound healing and tumorigenesis.
Structure and function
Microfilaments, mitochondria, and nuclei in fibroblast cells
Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli. Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. Inactive fibrocytes are smaller, spindle shaped, and have a reduced rough endoplasmic reticulum. Although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters.
Fibroblasts make collagens, glycosaminoglycans, reticular and elastic fibers, glycoproteins found in the extracellular matrix, and cytokine TSLP. Growing individuals' fibroblasts are dividing and synthesizing ground substance. Tissue damage stimulates fibrocytes and induces the mitosis of fibroblasts.
Unlike the epithelial cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a basal lamina on one side, although they may contribute to basal lamina components in some situations (e.g. subepithelial myofibroblasts in intestine may secrete the α-2 chain carrying component of the laminin 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.[3]
Immune System Functions
Initiation of 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 and provide a pathway for immune cells to regulate fibroblasts.[4]
Mediation of Tumors
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.[5] 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.[6] 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.[5]
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.[5]
Secondary actions
Mouse embryonic fibroblasts (MEFs) are often used as "feeder cells" in human embryonic stem cell research. However, many researchers are gradually phasing out MEFs in favor of culture media with precisely defined ingredients of exclusively human derivation[citation needed]. Further, the difficulty of exclusively using human derivation for media supplements is most often solved by the use of "defined media" where the supplements are synthetic and achieve the primary goal of eliminating the chance of contamination from derivative sources.
See also
- 3T3 cells
- Fibrocartilage callus
- Fibrous connective tissue
References
- ^ "Fibroblast". Genetics Home Reference. U.S. National Library of Medicine. 2014-05-05. Retrieved 2014-05-10.
- ^ Dave, Jui M.; Bayless, Kayla J. (May 2014). "Vimentin as an Integral Regulator of Cell Adhesion and Endothelial Sprouting". Microcirculation. 21 (4): 333–344. PMID 24387004. doi:10.1111/micc.12111.
- ^ Weissmanshomer, P.; Fry, M. (1975). "Chick embryo fibroblasts senescence in vitro: Pattern of cell division and life span as a function of cell density". Mechanisms of Ageing and Development. 4 (2): 159–166. PMID 1152547. doi:10.1016/0047-6374(75)90017-2.
- ^ Smith, R. S.; Smith, T. J.; Blieden, T. M.; Phipps, R. P. (1997-08-01). "Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation.". The American Journal of Pathology. 151 (2): 317–322. ISSN 0002-9440. PMC 1858004 . PMID 9250144.
- ^ a b c Silzle, Tobias; Randolph, Gwendalyn J.; Kreutz, Marina; Kunz-Schughart, Leoni A. (2004-01-10). "The fibroblast: Sentinel cell and local immune modulator in tumor tissue". International Journal of Cancer. 108 (2): 173–180. ISSN 1097-0215. doi:10.1002/ijc.11542.
- ^ Bonnans, Caroline; Chou, Jonathan; Werb, Zena (2017-02-02). "Remodelling the extracellular matrix in development and disease". Nature Reviews. Molecular Cell Biology. 15 (12): 786–801. ISSN 1471-0072. PMC 4316204 . PMID 25415508. doi:10.1038/nrm3904.
External links
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Wikimedia Commons has media related to Fibroblast. |
- UIUC Histology Subject 240
- MedEd at Loyola Histo/practical/ctproper/hp3-15.html
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Connective tissue
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| Physiology |
- Soft tissue
- Fibrosis
- Scarring
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| Composition |
| Cells |
| Resident |
- Fibroblast
- Fibrocyte
- Reticular cell
- Tendon cell
- Adipocyte
- Melanocyte
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| Wandering cells |
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Extracellular
matrix |
| Ground substance |
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| Fibers |
- Collagen fibers
- Reticular fibers: COL3A1
- Elastic fibers: Elastin
- Fibrillin
- EMILIN1
- Elaunin
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|
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| Classification |
| Proper |
| Loose |
|
| Dense |
- Dense irregular connective tissue
- Dense regular connective tissue
- Ligament
- Tendon
- Aponeurosis
|
|
| Embryonic |
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| Specialized |
|
|
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Cells in humans derived from mesoderm
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| Paraxial |
| Mesenchymal stem cell |
| Osteochondroprogenitor cell |
- Bone (Osteoblast → Osteocyte)
- Cartilage (Chondroblast → Chondrocyte)
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| Myofibroblast |
- Fat
- Muscle
- Myoblast → Myocyte
- Myosatellite cell
- Tendon cell
- Cardiac muscle cell
- Other
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| Other |
- Digestive system
- Interstitial cell of Cajal
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| Intermediate |
| Renal stem cell |
- Angioblast → Endothelial cell
- Mesangial cell
- Intraglomerular
- Extraglomerular
- Juxtaglomerular cell
- Macula densa cell
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- Stromal cell → Interstitial cell → Telocytes
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- Simple epithelial cell → Podocyte
- Kidney proximal tubule brush border cell
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| Reproductive system |
- Sertoli cell
- Leydig cell
- Granulosa cell
- Peg cell
- germ cells
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Lateral plate/
hemangioblast |
| Hematopoietic stem cell |
- Lymphoid
- Lymphoblast
- see lymphocytes
- Myeloid
- CFU-GEMM
- see myeloid cells
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| Circulatory system |
- Endothelial progenitor cell
- Endothelial colony forming cell
- Endothelial stem cell
- Angioblast/Mesoangioblast
- Pericyte
- Mural cell
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