I will be initiating a project to study therapeutic effects of immune engagers on HCC. If I want to study therapeutic effects of immune engagers against hepatocellular carcinoma, is it better to use an ectopic tumor mouse models or is it better to use HCC organoids? Can anyone tell me the best commercial source of liver cancer organoids and is ATCC a good option? Is use of human organoids in initial studies better than testing directly on ectopic or orthotropic HCC mouse models?
Hello Dirghau Manishbhai Patel
Liver organoids are ideal tools for HCC. But for the liver, improved organoid models reflecting the cell heterogeneity consisting not only hepatocytes and cholangiocytes but also inclusion of Kupffer cells and hepatic stellate cells is important. The lack of physiological complexity of organoid culture can be tackled by performing organoid co-culture approach. The tumor microenvironment (TME) plays a crucial role in tumorigenesis, as it has been identified to sustain and maintain tumor growth and metastasis. Of the cells circulating in the TME, the cancer-associated fibroblasts (CAFs) have been shown to support tumor growth and invasion and promote tumor resistance.
A co-culture between primary liver cancer-derived organoids and CAFs could provide a more reliable ex vivo liver cancer microenvironment model through direct cell-to-cell interaction between the tumor cells and CAFs.
On the other hand, ectopic implantation do not allow study of complex tumor–host interactions, but orthotopic implantation makes it possible to investigate the neoplastic hepatocytes in their natural environment. So, you should go for orthotropic HCC mouse models.
You may refer to the paper attached below which describes the formation strategies of liver organoids. Liver organoids may be derived from single type cell culture, such as induced pluripotent stem cells (iPSCs), adult stem cells, primary hepatocytes, and primary cholangiocytes and multi-type cells co-culture, such as iPSC-derived hepatic endoderm cells co-cultured with mesenchymal stem cells and umbilical cord-derived endothelial cells.
Article Liver Organoids: Formation Strategies and Biomedical Applications
Yes, the use of human organoids in initial studies is better than testing directly on orthotropic HCC mouse models though there are certain limitations such as lack of complete reconstitution of the cellular niche provided by neural, immune, and stromal cells limiting physiological relevance. Nevertheless, organoids are inherently heterogeneous, which more or less is a representative of in vivo tissue.
Yes, ATCC is a good option. ATCC should be having organoids from human small intestine, colon, esophagus, stomach, pancreas as well as liver. Please refer to the links below for more information on organoids.
https://www.atcc.org/resources/culture-guides/organoid-culture-guide#Intro
https://www.atcc.org/cell-products/collections-and-projects/human-cancer-models-initiative#t=productTab&numberOfResults=24
Best.
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