What you need to know about human liver cells

The liver is the largest and most complex internal organ in the human body, weighing approximately 1.5 Kg. It is involved in an array of vital functions that help support metabolism, immunity, and detoxification among other functions. Apart from functioning as a metabolic organ, it is also considered an exocrine gland that produces and secretes bile.

The liver is divided into two lobes, the large right lobe, and the smaller left lobe. Each lobe is further divided into hexagonally shaped lobules, which are the functioning units of the liver. Each lobule is made up of rows of hepatocytes and surrounded by branches of the hepatic artery (which provides oxygen) and the portal vein (which provides nutrients). These vessels drain into capillary-like structures called sinusoids, which exchange materials directly with the hepatocytes. The sinusoids drain into a central vein, which feeds deoxygenated blood into the hepatic vein.

The different types of liver cells and their research objective application

The liver is composed of four major cell types – hepatocytes, hepatic stellate cells, kupffer cells, and liver sinusoidal endothelial cells. Hepatocytes are the primary parenchymal cells, making up the largest (~70%) total liver population. These specialized epithelial cells exhibit highly polarized architecture and organization of the cytoplasm and plasma membrane, to fulfill the multitude of tasks they are required to perform. They are primarily engaged in functions ranging from gluconeogenesis, albumin secretion, and lipid metabolism to drug metabolism.

Hepatic stellate cells are perisinusoidal resident cells that are central to Vitamin A and lipid storage. They also contribute to liver homeostasis by secreting cytokines and growth factors. They are also the primary source of myofibroblasts to drive fibrogenic process in response to liver damage by secreting extracellular matrix (ECM) proteins.

The kupffer cells are specialized macrophages in the liver. They are found within the lumen of the liver sinusoids and are adhesive to their endothelial cells made up of blood vessel walls. Kupffer cells play an important role in maintaining liver function and act as an innate immune system to protect the liver. They play roles in host defense and tissue homeostasis by scavenging bacteria and cellular debris and inducing immunological tolerance.

The liver sinusoidal endothelial cells form the wall of the blood vessels (sinusoids) that carry blood throughout the liver. They play an important role in lipid metabolism, coagulation, cellular growth, differentiation, immunity, and inflammatory response.

Cell Sources for Hepatic Culture

There are various in vitro liver cell culture models under development for predictive models in drug development and research. The types of liver cells used in hepatic in vitro research depend on the study’s aim and design. The ease of obtaining and availability of the cells are also critical factors for deciding on the types and sources of cells used. Some of the common sources of liver cells include primary human hepatocytes, hepatic cell lines, and stem cell-derived hepatocytes.

• Primary Human Hepatocytes: Primary human hepatocytes are widely accepted as the gold standard for in vitro cell culture models for the evaluation of metabolism, drug-drug interactions, drug transporter activity, and toxicity of drug candidates. As the primary human hepatocytes closely resemble the cells in their natural environment functionally and genetically, they provide highly predictive results in pharmacological and toxicological in in vitro research. However, the availability of primary human hepatocytes is limited and is not easily accessible, and they tend to lose functionality and polarity rapidly unless cultured in particular conditions, such as the collagen sandwich format. Therefore, 3D culture provides a good platform for ECM-cell interactions and cell-cell interactions which help maintain the mature hepatocyte phenotype.

• Human Hepatic Cell Lines: Human hepatic cell lines are immortalized cells that can be cultured indefinitely in the laboratory. Several hepatocyte cell lines have been established, such as HepG2, HepaRG, and Huh-7, which are derived from human liver cancer or hepatoma cells. These cells have the advantage of high proliferation capacity, unlimited availability, reproducibility, batch-to-batch consistency, and cost-saving. However, these cell lines are generally associated with loss of differentiated functions, and thus show less liver-specific metabolism compared with normal adult liver cells.

• Human Stem Cell-Derived Hepatocytes: Hepatocytes can be derived from stem cells such as adult stem cells, or pluripotent stem cells such as human embryonic stem cells (hESC)and human induced pluripotent stem cells (hiPSCs). Stem cells are capable of self-renewing and differentiating into multiple lineages. They also offer the advantage of deriving from the patient’s own cells, hence allowing personalized disease modelling and drug testing.

Where can you get liver cells for your research in Singapore and other parts of Asia?

High-quality primary human hepatocytes are important for the success of creating a reliable and reproducible hepatic in vitro culture. Atlantis Bioscience is working with our esteemed partner, BeCytes Biotechnologies, in providing high-quality human primary hepatocytes isolated from the liver tissues of consenting living donors. The primary hepatocytes are available in fresh or cryopreserved, plateable or suspension formats, and qualified for metabolism, induction, transporter, or 3D culture.  

We also offer mix human non-parenchymal cells, human hepatic stellate cells, human endothelial cells, human kupffer cells, NASH hepatocytes, and hepatocytes from a wide range of animals.

All BeCytes products come with a certificate of analysis (CoA), including data related to the donor’s medical record and histological analysis from the tissue before isolation. It also includes the number of hepatocytes per vial and its viability post-thawing; as well as the optimal cell seeding concentration in different culture plates, the number of days in cultures, and morphology pictures. Information about the enzyme expression levels, induction studies, and spheroid formation of the hepatocytes is also available.

Find the right cell type and solutions that fit your research needs to help you go from bench to bed at Atlantis Bioscience.

References:

Xu Q. Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications. Front Bioeng Biotechnol. 2021;9:730008. Published 2021 Sep 24. doi:10.3389/fbioe.2021.730008

Zaefarian, F.; Abdollahi, M.R.; Cowieson, A.; Ravindran, V. Avian Liver: The Forgotten Organ. Animals 2019, 9, 63. https://doi.org/10.3390/ani9020063

Zeilinger K, Freyer N, Damm G, Seehofer D, Knöspel F. Cell sources for in vitro human liver cell culture models. Exp Biol Med (Maywood). 2016 Sep;241(15):1684-98. doi: 10.1177/1535370216657448. Epub 2016 Jul 5. PMID: 27385595; PMCID: PMC4999620.