Hepatotoxicity Evaluation by Liver Organoid Model

Hepatotoxicity is frequently the principal worry among numerous drug safety concerns because the liver is the pivotal organ in the body's biotransformation and removal of hazardous substances. Liver organoids help identify and classify hepatotoxic compounds in the early stages of drug development, resulting in safer drugs and a more streamlined drug development process. Creative Biolabs launches various liver organoid models to help customers with drug validation and hepatotoxicity assessment.

The Feature of the Liver Organoid Model

1	Reconstruct liver tissue structures in vitro.
2	Recapitulate the interactions between several types of cells in the organ during growth, homeostasis, or the progression of illness.
3	Higher biosimilarity, including multiple cell types.
4	Improve the physiological processes of the liver cells by simulating the tissue niche.
5	Promote both in vitro and in vivo vascularization of organoids.

Several Ways to Construct the Liver Organoid Model

Tissue-derived Biliary and Hepatic Organoids

Bipotent biliary organoids that have been extracted from patient liver tissue and are in the process of proliferating can be kept in culture as an expanding cell source and can be differentiated into useful cholangiocytes or hepatocytes.
Hepatocytes were isolated from liver tissue. These proliferating hepatocytes have the potential to develop into highly functioning hepatocytes.
Fibroblast differentiation into liver organoids. The fibroblast over-expressing SV40 large T antigen is transdifferentiated into human-induced hepatocyte organoids (HiHeps) in combination with FOXA3, HNF1A, and HNF4A. When different HCC oncogenes are introduced, HiHeps become liver cancer organoids.

Biliary organoids from patient liver tissue, being proliferating and bipotent, can be cultured as an expandable cell source and differentiated into cholangiocytes or hepatocytes. Fig.1 Stem cell and progenitor liver organoids.¹

Liver Cancer Organoids

Isolation of cancer organoids from the three most frequent kinds of liver tumors: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and hepato-cholangiocarcinoma.
The use of functional human-induced Hiheps derived from immortalized fibroblasts with the SV40 big T antigen, whose antigen inactivates p53 and Rb proteins. The HiHeps undergo an oncogenic transformation and develop tumors when engrafted when the Myc oncogene is overexpressed later.

Pluripotent Stem Cell-derived Liver Organoids

The most popular method for producing organ-like structures in a dish is to imitate organogenesis, which occurs during embryonic development. This method makes use of past knowledge gleaned from differentiation studies conducted with PSCs. PSCs' aptitude for self-renewal and developmental potential encouraged the use of these cells to create organoids that resembled various human organs.

PSC-derived liver organoids. Fig.2 Pluripotent stem cell (PSC) derived liver organoids.¹

Bio-engineered Liver Organoids

The use of one or more of these approaches in conjunction with various types of liver cells (primary cells, immortalized cell lines, and stem cell-derived hepatic cells).

Different parenchymal and non-parenchymal liver cell types have been employed with a variety of engineering tools to create bio-engineered liver organoids. Fig.3 Engineering approaches to create liver organoids.¹

Creative Biolabs' liver organoids contribute to the creation of safer pharmaceuticals and facilitate a more efficient drug development pathway. If you have related needs, please contact us for more information.

Reference

Lam, Do Thuy Uyen Ha et al. "Emerging liver organoid platforms and technologies." Cell regeneration (London). 10,1 (2021): 27. Distributed under Open Access license CC BY 4.0, without modification.

Research Model

3D Biology Based Biomarker Discovery

3D Biology Based Drug Discovery and Development

3D Biology Based Toxicity Evaluation

Supporting Assays

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