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Review
. 2020 Mar 30;9(4):832.
doi: 10.3390/cells9040832.

Cholangiocarcinoma Disease Modelling Through Patients Derived Organoids

Francesco Amato  1 , Colin Rae  1 , Maria Giuseppina Prete  1 , Chiara Braconi  1   2
Affiliations
Review

Cholangiocarcinoma Disease Modelling Through Patients Derived Organoids

Francesco Amato et al. Cells. .

Abstract

Cancer organoids are 3D phenotypic cultures that can be established from resected or biopsy tumour samples and can be grown as mini tumours in the dish. Flourishing evidence supports the feasibility of patient derived organoids (PDO) from a number of solid tumours. Evidence for cholangiocarcinoma (CCA) PDO is still sparse but growing. CCA PDO lines have been established from resected early stage disease, advanced cancers and highly chemorefractory tumours. Cancer PDO was shown to recapitulate the 3D morphology, genomic landscape and transcriptomic profile of the source counterpart. They proved to be a valued model for drug discovery and sensitivity testing, and they showed to mimic the drug response observed in vivo in the patients. However, PDO lack representation of the intratumour heterogeneity and the tumour-stroma interaction. The efficiency rate of CCA PDO within the three different subtypes, intrahepatic, perihilar and distal, is still to be explored. In this manuscript we will review evidence for CCA PDO highlighting advantages and limitations of this novel disease model.

Keywords: CCA; PDO; biliary cancer; organoid; personalized medicine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Organoids establishment from different cell sources and their downstream applications. Organoids can be originated from different sources: ESCs, ASCs, iPSCs and primary tissue. The embedding of these cells in a basal membrane (BM), mostly represented by Matrigel, with appropriate growth factors has been reported to give rise to cholangiocytes [9] intestinal [3], hepatobiliary [10] organoids and lung [7]. For the capability to recapitulate 3D architecture, genotype and the histomorphology of the in vivo counterpart these constructs can be exploited for (a) disease modelling, (b) drug screening and precision medicine. Given their genome stability and the possibility to establish an organotypic culture with patient cells, organoids also showed to be a promising tissue source for regenerative medicine (c).
Figure 2
Figure 2
Patient derived organoid (PDO) lines from biliary tract malignancies. Graphic representation of four types of biliary tract malignancies with relative PDO lines generated so far for GBC [5] and iCCA (from top to bottom of the box [4,5,14], [32], [35], [36]). (N: number of patients; n: number of PDO lines).
See this image and copyright information in PMC

References

    1. Clevers H. Review Modeling Development and Disease with Organoids. Cell. 2016;165:1586–1597. doi: 10.1016/j.cell.2016.05.082. - DOI - PubMed
    1. Murrow L.M., Weber R.J., Gartner Z.J. Dissecting the stem cell niche with organoid models: An engineering-based approach. Development. 2017:998–1007. doi: 10.1242/dev.140905. - DOI - PMC - PubMed
    1. Sato T., Vries R.G., Snippert H.J., Van De Wetering M., Barker N., Stange D.E., Van Es J.H., Abo A., Kujala P., Peters P.J., et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;459:262–265. doi: 10.1038/nature07935. - DOI - PubMed
    1. Broutier L., Mastrogiovanni G., Verstegen M.M.A., Francies H.E., Gavarró L.M., Bradshaw C.R., Allen G.E., Arnes-Benito R., Sidorova O., Gaspersz M.P., et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat. Med. 2017;23:1424–1435. doi: 10.1038/nm.4438. - DOI - PMC - PubMed
    1. Saito Y., Muramatsu T., Kanai Y., Ojima H., Sukeda A., Hiraoka N., Arai E., Sugiyama Y., Matsuzaki J., Uchida R., et al. Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma. Cell Rep. 2019;27:1265–1276. doi: 10.1016/j.celrep.2019.03.088. - DOI - PubMed

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