Patient‐derived organoids of cholangiocarcinoma

Christopher Fabian Maier, Lei Zhu, Lahiri Kanth Nanduri, Daniel Kühn, Susan Kochall, May Linn Thepkaysone, Doreen William, Konrad Grützmann, Barbara Klink, Johannes Betge, Jürgen Weitz, Nuh N. Rahbari, Christoph Reißfelder, Sebastian Schölch*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Cholangiocarcinoma (CC) is an aggressive malignancy with an inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are extremely rare, this manuscript reports a protocol of cholangiocarcinoma patient‐derived organoid culture as well as a protocol for the transition of 3D organoid lines to 2D cell lines. Tissue samples of non‐cancer bile duct and cholangiocarcinoma were obtained during surgical resection. Organoid lines were generated following a standardized protocol. 2D cell lines were generated from established organ-oid lines following a novel protocol. Subcutaneous and orthotopic patient‐derived xenografts were generated from CC organoid lines, histologically examined, and treated using standard CC proto-cols. Therapeutic responses of organoids and 2D cell lines were examined using standard CC agents. Next‐generation exome and RNA sequencing was performed on primary tumors and CC organoid lines. Patient‐derived organoids closely recapitulated the original features of the primary tumors on multiple levels. Treatment experiments demonstrated that patient‐derived organoids of cholangiocarcinoma and organoid‐derived xenografts can be used for the evaluation of novel treat-ments and may therefore be used in personalized oncology approaches. In summary, this study establishes cholangiocarcinoma organoids and organoid‐derived cell lines, thus expanding translational research resources of cholangiocarcinoma.

Original languageEnglish
Article number8675
JournalInternational Journal of Molecular Sciences
Volume22
Issue number16
DOIs
Publication statusPublished - 2 Aug 2021
Externally publishedYes

Keywords

  • Cholangiocarcinoma
  • Next‐generation sequencing
  • Organoids
  • Orthotopic xenograft
  • Patient‐derived organ-oids
  • Precision medicine
  • Response prediction
  • Translational surgical oncology
  • Xenograft model

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