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.
Highlights
Organoids are microscopic three-dimensional (3D) tissue-like structures that outgrow from primary tissue explants or from single cells
While embryonic stem cells (ESCs)- and induced pluripotent stem cells (iPSCs)-derived organoids recapitulate embryonic developmental processes, organoids derived from adult stem cells (ASCs) represent a diversity of organotypic cultured tissues [1,2], where tissue homeostasis, or its disruption during disease, is recapitulated
Organoids can be originated from different sources: ESCs, ASCs, iPSCs and primary tissue
Summary
Organoids are microscopic three-dimensional (3D) tissue-like structures that outgrow from primary tissue explants or from single cells. 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 showed to be a promising tissue source for regenerative medicine (c)
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