A hepatocyte is a cell of the main parenchyma
l tissue of the liver
. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrate
* Synthesis of cholesterol
, bile salts
* Detoxification, modification, and excretion of exogenous and endogenous substances
* Initiation of formation and secretion of bile
The typical hepatocyte is cubical with sides of 20-30 μm
, (in comparison, a human hair
has a diameter of 17 to 180 μm).
[The diameter of human hair ranges from 17 to 181 μm. ]
The typical volume of a hepatocyte is 3.4 x 10−9
Smooth endoplasmic reticulum
is abundant in hepatocytes, whereas most cells in the body have only small amounts.
Hepatocytes display an eosinophilic
cytoplasm, reflecting numerous mitochondria
, and basophilic
stippling due to large amounts of smooth endoplasmic reticulum
and free ribosomes
. Brown lipofuscin
granules are also observed (with increasing age) together with irregular unstained areas of cytoplasm; these correspond to cytoplasmic glycogen
stores removed during histological preparation. The average life span of the hepatocyte is 5 months; they are able to regenerate
are round with dispersed chromatin
and prominent nucleoli
. Anisokaryosis (or variation in the size of the nuclei) is common and often reflects tetraploidy
and other degrees of polyploidy
, a normal feature of 30-40% of hepatocytes in the adult human liver. Binucleate cells
are also common.
Hepatocytes are organised into plates separated by vascular channels (sinusoids
), an arrangement supported by a reticulin
(collagen type III
) network. The hepatocyte plates are one cell thick in mammals and two cells thick in the chicken. Sinusoids display a discontinuous, fenestrated endothelial
cell lining. The endothelial cells have no basement membrane
and are separated from the hepatocytes by the space of Disse
, which drains lymph
into the portal tract lymphatics
s are scattered between endothelial cells; they are part of the reticuloendothelial system
and phagocytose spent erythrocytes
. Stellate (Ito) cells
store vitamin A
and produce extracellular matrix
; they are also distributed amongst endothelial cells but are difficult to visualise by light microscopy.
The hepatocyte is a cell
in the body
that manufactures serum albumin
, and the prothrombin
group of clotting factor
s (except for Factors 3 and 4).
It is the main site for the synthesis of lipoprotein
, and glycoprotein
Hepatocytes manufacture their own structural proteins and intracellular enzyme
Synthesis of proteins is by the rough endoplasmic reticulum
(RER), and both the rough and 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.
forms fatty acids from carbohydrate
s and synthesizes triglycerides from fatty acids and glycerol.
Hepatocytes also synthesize apoprotein
s with which they then assemble and export lipoproteins (VLDL
The liver is also the main site in the body for gluconeogenesis
, the formation of carbohydrates from precursors such as alanine
, and oxaloacetate
The liver receives many lipid
s from the systemic circulation and metabolizes chylomicron
It also synthesizes cholesterol
and further synthesizes bile salt
The liver is the sole site of bile salts formation.
Hepatocytes have the ability to metabolize, detoxify, and inactivate exogenous compounds such as drugs
(see drug metabolism
s, and endogenous compounds such as steroid
The drainage of the intestinal 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
The most abundant organelle in liver cells is the smooth endoplasmic reticulum
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 whole liver or liver tissue by collagenase
digestion, which is a two-step process. In the first step, the liver is placed in an isotonic
solution, in which calcium is removed to disrupt cell-cell 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. Freshly-isolated hepatocytes that are not used immediately can be cryopreserved
and stored. 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 cryoprotectant
s there is still damage done while being cryopreserved. Nevertheless, recent cryopreservation and resuscitation protocols support application of cryopreserved hepatocytes for most biopharmaceutical applications.
File:Hepato-biliary.jpg|Schemic diagram of Biliary system
*List of human cell types derived from the germ layers
* - "Ultrastructure of the Cell: hepatocytes and sinusoids"
Hepatic Histology: Hepatocytes (Colorado State University