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HP2 Heps 20 Human Pooled Primary Hepatocytes
Cat.No.: CSC-C4109X
Species: Human
Source: Liver
Cell Type: Hepatocyte
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Cell Features:
Each donor's hepatocytes have been cryopreserved ONCE immediately after isolation and purification.
Pools of 10 or 20 donors are available. Each donor is represented by a statistically significant number of cells relative to the pool.
There is extensive quality control providing characterization of viability and enzyme activity from both individual donors and the total pool.
Creative Bioarray guarantees performance and quality.
Donor information is available.
Creative Bioarray's HP2 Heps 20 human pooled primary hepatocytes is a composite of primary hepatocytes derived from 20 adult liver donors. This heterogeneous pool includes cells from donors of varying genders, ages, and health conditions, thus eliminating potential inter-donor variability and resulting in greater functional, activity, and phenotypic consistency. Consequently, this diversified cell pool offers broader population representativity and has extensive applications in drug metabolism, cytotoxicity, disease pathology, regenerative medicine, and personalized medicine.
In drug metabolism studies, pooled hepatocytes can more accurately simulate interindividual variability, aiding researchers in understanding the metabolic pathways that drugs undergo in the human body. Furthermore, they faithfully replicate the complex physiological environment of the human liver, providing a comprehensive enzyme profile that includes the cytochrome P450 enzyme system and other drug-metabolizing enzymes, which are critical for assessing drug metabolic rates and pathways. In disease model construction, pooled hepatocytes offer a more stable and genetically diverse model, thus better simulating the complexity of the human liver. This allows researchers to develop disease models that closely approximate real-life conditions, essential for studying disease mechanisms and evaluating drug efficacy. Additionally, pooled hepatocytes exhibit enhanced regenerative capabilities. Since they incorporate cells from multiple donors, they are instrumental in studying cell interactions and environmental factors during liver regeneration. Moreover, they provide a high-quality cell source for developing bioartificial livers and 3D bioprinting technologies, making them valuable assets in liver tissue engineering and regenerative medicine, with vast potential for future research and application.
Fig. 1. Primary culture of adult hepatocytes (Joshi M G, Gadgil A, et al., 2014).
Heterocyclic Amines Disrupt Lipid Homeostasis in Cryopreserved Human Hepatocytes
Heterocyclic amines (HCAs) are mutagens formed when cooking meat at high temperatures. Previous research has linked HCA exposure to insulin resistance and type II diabetes, but its effects on hepatic lipid dynamics were unexplored. Walls et al. tested two HCAs, MeIQx and PhIP on lipid homeostasis in cryopreserved human hepatocytes.
The results showed a significant increase in lipid droplets and neutral lipid content in human hepatocytes after treatment with MeIQx and PhIP (Fig. 1A-C). Changes in lipid droplet-associated gene expression revealed that patatin-like phospholipase domain-containing protein 3 (PNPLA3) and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) expression significantly increased in human hepatocytes after PhIP treatment, but not after MeIQx treatment (Fig. 1D-E). Perilipin 2 (PLIN2). significantly increased after both PhIP and MeIQx treatment (Fig. 1F). Neutral lipids mainly consist of triglycerides and cholesterol esters.
Neutral lipids mainly consist of triglycerides and cholesterol esters. They next examined the expression of triglycerides and related genes. The results showed no significant change in triglyceride content after MeIQx treatment, while the content significantly increased after PhIP treatment. Fatty acid synthase (FAC) and a cluster of diferentiation 36 (CD36) significantly increased only after PhIP treatment, whereas stearoyl-CoA desaturase (SCD) significantly increased only after MeIQx treatment, and diacylglycerol O-acyltransferase 2 (DGAT2) significantly increased after both MeIQx or PhIP treatment. Carnitine palmitoyltransferase 1A (CPT1A) significantly decreased after PhIP treatment (Fig. 2A-G). Total cellular cholesterol content detection showed that content the in human hepatocytes significantly increased after MeIQx and PhIP treatment, while the expression of PON1, a gene encoding a protein that stimulates cholesterol efflux, significantly decreased (Fig. 2H-I).
Fig. 1. Lipid droplet and neutral lipid accumulation following HCA exposure in cryopreserved human hepatocytes (Walls, K. M., Joh, J. Y., et al., 2024).
Fig. 2. Changes in intracellular triglycerides and expression of genes involved in lipid synthesis and metabolism (A-G) and cholesterol and PON1 (H-I) following HCA exposure in cryopreserved human hepatocytes (Walls, K. M., Joh, J. Y., et al., 2024).
In Vitro Metabolism of Evodiamine in Human Liver Microsomes and Hepatocytes
Evodiamine is an indoloquinazoline alkaloid isolated from the fruit of Evodia rutaecarpa and possesses anti-tumor and anti-inflammatory properties. Detailed analyses of its metabolites have not yet been reported. Zhang et al. used UHPLC-Q exactive mass spectrometry to identify the metabolites of evodiamine after incubation with human liver microsomes and hepatocytes, exploring its metabolic pathways in the human body.
The results showed that there were four pathways for the metabolism of evodiamine in human liver microsomes and hepatocytes. The first pathway is oxidation of indole moiety to form oxygenated metabolites M1 and M9, which undergo further metabolism to form GSH conjugates (M3 and M4) via reactive quinone-imine intermediate, to form glucuronide conjugates (M5 and M10), and to form di-oxygenation metabolites (M11 and M13). The second pathway is oxidation of C-3 position to form M2, which were further metabolized via oxygenation, glucuronidation and N-demethylation to form M6, M7, and M8, respectively. The third metabolic pathway is N-demethylation to form M16, which was further metabolized into oxygenated metabolites (M8, M17, M18, and M19). The fourth metabolic pathway is direct conjugation with GSH via reactive imine-methide intermediate to form GSH adducts (M14 and M15). Therefore, oxygenation, demethylation, GSH conjugation, and glucuronidation were the predominant metabolic pathways of evodiamine in human liver microsomes and hepatocytes.
Fig. 3. Proposed metabolic pathways of evodiamine in human hepatocytes and liver microsomes (Zhang, Z., Fang, T., et al., 2018).
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Description: Bioarray offers an assortment of various human and non-human hepatic derived cells. These include Hepatocytes, Total Liver Cell Population (TLC), Stellates, Progenitors and Intra-hepatic biliary epithelial cells. We offer these as cryopreserved cells for convenience. Cryopreserved cells are suitable for a variety of assays including induction, toxicity, drug metabolism and systems biology. Both adherent and suspension cells are available. Custom configurations are available upon request.
Description: Bioarray offers an assortment of various human and non-human hepatic derived cells. These include Hepatocytes, Total Liver Cell Population (TLC), Stellates, Progenitors and Intra-hepatic biliary epithelial cells. We offer these as cryopreserved cells for convenience. Cryopreserved cells are suitable for a variety of assays including induction, toxicity, drug metabolism and systems biology. Both adherent and suspension cells are available. Custom configurations are available upon request.
Description: Bioarray offers an assortment of various human and non-human hepatic derived cells. These include Hepatocytes, Total Liver Cell Population (TLC), Stellates, Progenitors and Intra-hepatic biliary epithelial cells. We offer these as cryopreserved cells for convenience. Cryopreserved cells are suitable for a variety of assays including induction, toxicity, drug metabolism and systems biology. Both adherent and suspension cells are available. Custom configurations are available upon request.
Description: Bioarray offers an assortment of various human and non-human hepatic derived cells. These include Hepatocytes, Total Liver Cell Population (TLC), Stellates, Progenitors and Intra-hepatic biliary epithelial cells. We offer these as cryopreserved cells for convenience. Cryopreserved cells are suitable for a variety of assays including induction, toxicity, drug metabolism and systems biology. Both adherent and suspension cells are available. Custom configurations are available upon request.
Description: Bioarray offers an assortment of various human and non-human hepatic derived cells. These include Hepatocytes, Total Liver Cell Population (TLC), Stellates, Progenitors and Intra-hepatic biliary epithelial cells. We offer these as cryopreserved cells for convenience. Cryopreserved cells are suitable for a variety of assays including induction, toxicity, drug metabolism and systems biology. Both adherent and suspension cells are available. Custom configurations are available upon request.
