Summarization on present status of current organoids research for liver cancer

Organoids for Study of Liver Cancer

As already mentioned, the use of organoids in the assessment of developmental pathophysiology is confirmed and applied in several branches of medicine.[12] Starting from potent stem cell, the organoids development using advanced stem cell technology can help derive a model that can reflect the developmental process of organ in living things.[12] In hepatology, the development of organoids model is already successful. As noted by Xu et al., “Together with efficient gene-editing protocol, organoids are emerging as powerful in vitro disease models.”[13] In fact, the organoids model for liver is a new thing and actual new development in hepatology.[14] [15] At present, a small liver cell can be harvested and further used for cell processing by stem cell technology to provide liver organoids that can be able for further pathophysiology study.[14] [15] Mitaka and Ooe noted that the liver organoids is a realistic cellular model since it can represent the liver tissue’s physiological and biochemical functions.[15] Therefore, the study of several complex hepatic disorders can be based on the organoids model. This can be applied for several liver diseases including genetic, infectious, and cancer liver diseases.

In this short article, the author will focus on the cancerous problem. In fact, the study on liver cancer has been performed in clinical medicine and medical science for a long time. Within the past few years, there are many interesting new emerging advanced technologies that help better assess on the liver cancer. Of several new technologies, the advanced cell technologies for assessment of liver cancer, organoids technology is very interesting. As noted by Gao and Chen, “cancer ’organoid’ culture conditions have been developed to establish in vitro growth of patient-derived samples at higher efficiency and they are very promising for large-scale drug screening and fundamental cancer biology research.”[16] The author summarizes and discusses on applied organoids technology for studying on various kinds of liver cancers. The application can be seen on primary hepatocellular carcinoma, secondary liver cancer, metastatic liver cancer, cholangiocarcinoma, hepatoblastoma, as well as other rare liver cancers.

Use of Organoids in Pre-Liver Cancer Condition

Viral hepatitis

Viral hepatitis is accepted as an important underlying cause of liver cancer. The hepatitis B virus and hepatitis C virus infections are confirmed as the major causes of liver cancer worldwide.[17] [18] The application of organoids technique in viral hepatitis is very interesting. Nevertheless, according to the literature review, there are extremely few reports on organoids research for viral hepatitis. A possible reason might be the advanced molecular technology already helps clarify most problem of pathophysiology of viral hepatitis. Nevertheless, there is a recent interesting research on using organoids technique to study the antiviral drug for hepatitis C virus infection in the case of Zika virus infection,[19] which is an actual further application of organoids research on viral hepatitis.

Alcoholic hepatitis

Focusing on alcoholic hepatitis, it is also accepted as an important cause of liver cancer. Similar to viral hepatitis, there are extremely limited reports on organoids research for alcoholic hepatitis. According to the record in database (Scopus and PubMed), there is no report on organoids research on alcoholic hepatitis.

Use of Organoids in Different Kinds of Liver Cancer

Primary hepatocellular carcinoma

Organoids research on primary hepatocellular carcinoma is an actual applied organoids technique in oncology.[20] For hepatocellular carcinoma research, organoids can be used for the assessment on genetic backgrounds. In addition, the disease modeling can further be useful for finding a proper personalized cancer therapy planning.[21] The first requirement that brings success for the use of organoids tool in primary hepatocellular carcinoma research is the success in the development of effective organoids model. For example, in 2006, there was a report on the successful development of a new liver organoids based on a functional human hepatocellular carcinoma cell line.[22] The organoids model in that study also made use of mouse cell lines for generation. This model is the basic reference for further organoids development for primary hepatocellular research.

Another interesting model was proposed by Kobayashi et al. in 2013.[23] Kobayashi et al. used advanced stem cell technology to manipulate hepatocytes and fibroblasts accompanied with primary hepatocellular carcinoma cell line to form the organoids model.[23]

In addition to the organoids model development, the actual applied of the developed model is very interesting. First, the study on genetic underlying of hepatocellular carcinoma is a good example of application of organoids technique for pathophysiological study of primary hepatocellular carcinoma. Crosas-Molist et al. studied on the interrelationship between oncogene and hepatoma by mean of organoids model and concluded the cellular pathophysiological mechanism of tumor aggressiveness of primary hepatocellular carcinoma.[24] Second, the study on cancer therapy for primary hepatocellular carcinoma by organoids technique should also be mentioned. In fact, the attempt of using spheroids technique, which is a preorganoids development, for study in anticancerous agent has been published for many years.[25] For organoids, Lu et al. recently reported on anticancer effect of triterpenoid preparation using organoids model.[26] Lu et al. found that triterpenoid preparation had strong cytotoxic effect and also identified drug–drug interaction according to the studied preparation.[26] This report by Lu et al.[26] is a good example of report from organoids technique that might be further useful in new anticancer drug search.

Secondary liver cancer

The secondary liver cancer, caused by cancer metastatic cells from other primary origin, due to other cancer is a common problem in oncology since the liver is the common site of cancer metastasis. Skardal et al. recently reported an interesting organoids technique research on secondary liver cancer.[27] Skardal et al. reported the success in developed organoids model of secondary liver cancer due to colon cancer metastasis and mentioned for using the potential of in vitro 3D liver-tumor organoids for serving as a model for metastasis growth as well for assessment the response of malignant cells to present and newly launched drugs.[26]

Metastatic liver cancer

The metastasis of primary hepatocellular carcinoma is a common problem in advanced primary hepatocellular carcinoma. Metastatic liver cancer, caused by metastatic liver cancer cells in another organ, is difficult to manage in oncology. Although there is a success in organoids development for metastatic cancer model, such as model for metastatic colorectal cancer,[28] there is still no report on the success on the development of organoids model of metastatic liver cancer

Cholangiocarcinoma

Cholangiocarcinoma is a common biliary tract cancer. The intrahepatic cholangiocarcinoma is a deadly liver cancer with a poor prognosis. In tropical Southeast Asia, the relationship between cholangiocarcinoma and liver fluke infestation is confirmed.[29] [30] Focusing on the use of organoids model for cholangiocarcinoma research, there is still no report on success in the development of organoids model for cholangiocarcinoma.

Hepatoblastoma

Hepatoblastoma is an important kind of liver cancer seen in pediatric hepatology. The application of organoids research on this liver cancer is limited. Nevertheless, there is an interesting report on using spheroids technique.[31] In that study, Kosaka et al. successfully used spheroid cultures of human hepatoblastoma cells for studying on alcoholic toxicity and development of cancer.[31] The future organoids development can be referred to the basic information from the study by Kosaka et al.[31]

Hepatic lymphoma

Hepatic lymphoma is a rare type of liver cancer.[32] Although the development of organoids model for lymphoma is successful,[33] there is still no application on organoids research for hepatic lymphoma.

Conclusion

Organoids is a new cellular technology with used on stem cell knowledge for modeling realistic model to reflect medical disorder. It can be useful for cellular developmental pathophysiology study. In hepatology research, the new advanced organoids tool can be very useful on the etiopathophysiology study of several liver problems including liver cancer. It is widely applied for studying on several precancer conditions and several kinds of liver cancer. The rapid progression of the cell biotechnology can be seen and this is very useful for liver cancer pathophysiology and therapeutic research. Although the development and maintenance of organoids is still a big technical problem for many settings, the use of this new cellular tool warrants further attempt of the medical scientist who works on liver cancer research to learn, develop, and use the organoids technique for hepatic cancer research and development. The organoids is an actual hope for the future in hepatology. Nevertheless, it is still far incomplete in terms of coverage of models. It should be well clarified that there are several types of organoid culture. Sometimes, the effectiveness of technique is due to the difference of transport phenomena and diffusion limitation. It is still the interesting topic for further study on required culture condition for the truly effective organoids.

Conflict of Interest

There are no conflicts of interest.

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Publication History

Article published online:
17 June 2021

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