Hepatocyte

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Hepatocyte
Hepatocyte and sinusoid (venule) in a section of rat liver
Details
LocationLiver
Identifiers
MeSHD022781
THH3.04.05.0.00006
FMA14515
Anatomical terms of microanatomy

A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in:

Structure

The typical hepatocyte is cubical with sides of 20-30 

human hair has a diameter of 17 to 180 μm).[1] The typical volume of a hepatocyte is 3.4 x 10−9 cm3.[2]
Smooth endoplasmic reticulum is abundant in hepatocytes, in contrast to most other cell types.[3]

Microanatomy

Hepatocytes display an

ribosomes. Brown lipofuscin granules are also observed (with increasing age) together with irregular unstained areas of cytoplasm; these correspond to cytoplasmic glycogen and lipid stores removed during histological preparation. The average life span of the hepatocyte is 5 months; they are able to regenerate
.

Hepatocyte

tetraploidy and other degrees of polyploidy, a normal feature of 30-40% of hepatocytes in the adult human liver.[4] Binucleate cells
are also common.

Hepatocytes are organised into plates separated by vascular channels (

lymphatics
.

light microscopy.

Function

Protein synthesis

The hepatocyte is a

clotting factors
(except for Factors 3 and 4).

It is the main site for the synthesis of lipoproteins, ceruloplasmin, transferrin, complement, and glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes.

Synthesis of proteins is by the

smooth endoplasmic reticulum
(SER) are involved in secretion of the proteins formed.

The endoplasmic reticulum (ER) is involved in conjugation of proteins to lipid and carbohydrate moieties synthesized by, or modified within, the hepatocytes.

Proteins produced by hepatocytes that function as hormones are known as hepatokines.

Carbohydrate metabolism

See also: Lipogenesis

The liver forms fatty acids from carbohydrates and synthesizes triglycerides from fatty acids and glycerol.[5] Hepatocytes also synthesize

HDL
).

The liver is also the main site in the body for

oxaloacetate
.

Lipid metabolism

The liver receives many lipids from the systemic circulation and metabolizes chylomicron remnants. It also synthesizes

bile salts
. The liver is the sole site of bile salts formation.

Detoxification

Hepatocytes have the ability to metabolize, detoxify, and inactivate exogenous compounds such as drugs (see drug metabolism), insecticides, and endogenous compounds such as steroids.

The drainage of the

venous blood into the liver requires efficient detoxification of miscellaneous absorbed substances to maintain homeostasis
and protect the body against ingested toxins.

One of the detoxifying functions of hepatocytes is to modify ammonia into urea for excretion.

The most abundant organelle in liver cells is the

smooth endoplasmic reticulum
.

Aging

As mammalian liver cells age,

7-methylguanine) increase with age.[6] Also, in rat liver, DNA single- and double-strand breaks, oxidized bases, and methylated bases increase with age; and in rabbit liver, cross-linked bases increase with age.[6] Liver cells depend on DNA repair pathways that specifically protect the transcribed compartment of the genome to promote sustained functionality and cell preservation with age.[7]

Society and culture

Use in research

Primary hepatocytes are commonly used in cell biological and biopharmaceutical research. In vitro model systems based on hepatocytes have been of great help to better understand the role of hepatocytes in (patho)physiological processes of the liver. In addition, pharmaceutical industry has heavily relied on the use of hepatocytes in suspension or culture to explore mechanisms of drug metabolism and even predict in vivo drug metabolism. For these purposes, hepatocytes are usually isolated from animal or human

tight junctions by the use of a calcium chelating agent. Next, a solution containing collagenase is added to separate the hepatocytes from the liver stroma. This process creates a suspension of hepatocytes, which can be seeded in multi-well plates and cultured for many days or even weeks. For optimal results, culture plates should first be coated with an extracellular matrix (e.g. collagen, Matrigel) to promote hepatocyte attachment (typically within 1-3 hr after seeding) and maintenance of the hepatic phenotype. In addition, and overlay with an additional layer of extracellular matrix is often performed to establish a sandwich culture of hepatocytes. The application of a sandwich configuration supports prolonged maintenance of hepatocytes in culture.[9][10] Freshly-isolated hepatocytes that are not used immediately can be cryopreserved and stored.[11] They do not proliferate in culture. Hepatocytes are intensely sensitive to damage during the cycles of cryopreservation including freezing and thawing. Even after the addition of classical cryoprotectants there is still damage done while being cryopreserved.[12] Nevertheless, recent cryopreservation and resuscitation protocols support application of cryopreserved hepatocytes for most biopharmaceutical applications.[13]

Additional images

  • Schemic diagram of Biliary system
    Schemic diagram of Biliary system

See also

References

  1. ^ The diameter of human hair ranges from 17 to 181 μm. Ley, Brian (1999). Elert, Glenn (ed.). "Diameter of a human hair". The Physics Factbook. Retrieved 2018-12-08.
  2. ^ Lodish, H., Berk, A., Zipursky, S. L., Matsudaira, P., Baltimore, D., Darnell, J. E. Molecular Cell Biology (Fifth Edition). W. H. Freeman and Company. New York, 2000, pp 10.
  3. OCLC 663096046
    .
  4. S2CID 22708555. Archived from the original
    (PDF) on 2012-04-25.
  5. PMID 27178543
    .
  6. ^ a b Holmes GE, Bernstein C, Bernstein H. Oxidative and other DNA damages as the basis of aging: a review. Mutat Res. 1992 Sep;275(3-6):305-15. doi: 10.1016/0921-8734(92)90034-m. PMID: 1383772
  7. ^ Vougioukalaki M, Demmers J, Vermeij WP, Baar M, Bruens S, Magaraki A, Kuijk E, Jager M, Merzouk S, Brandt RMC, Kouwenberg J, van Boxtel R, Cuppen E, Pothof J, Hoeijmakers JHJ. Different responses to DNA damage determine ageing differences between organs. Aging Cell. 2022 Apr;21(4):e13562. doi: 10.1111/acel.13562. Epub 2022 Mar 4. PMID: 35246937; PMCID: PMC9009128
  8. PMID 20645046
    .
  9. S2CID 449420
    . Erratum in: FASEB J 1989 May;3(7):1873.
  10. S2CID 27593521
    .
  11. PMID 11267922
    .
  12. S2CID 4981423
    .
  13. PMID 21605667
    .

External links
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