A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids

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  • Matías Marín Falco
  • Yilin Li
  • Kari Lavikka
  • Mette C. Kriegbaum
  • Jaana Oikkonen
  • Elin J. Pietras
  • Erdogan Pekcan Erkan
  • Jun Dai
  • Anastasia Lundgren
  • Tarja Lamminen
  • Katja Kaipio
  • Jutta Huvila
  • Anni Virtanen
  • Pernille Christiansen
  • Kaisa Huhtinen
  • Olli Carpén
  • Johanna Hynninen
  • Sampsa Hautaniemi
  • Anna Vähärautio

The broad research use of organoids from high-grade serous ovarian cancer (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here, we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (53% vs. 23%–38%). We established organoids from cryopreserved material, demonstrating the feasibility of using viably biobanked tissue for HGSC organoid derivation. Genomic, histologic, and single-cell transcriptomic analyses revealed that organoids recapitulated genetic and phenotypic features of original tumors. Organoid drug responses correlated with clinical treatment outcomes, although in a culture conditions-dependent manner and only in organoids maintained in human plasma-like medium (HPLM). Organoids from consenting patients are available to the research community through a public biobank and organoid genomic data are explorable through an interactive online tool. Taken together, this resource facilitates the application of HGSC organoids in basic and translational ovarian cancer research.

OriginalsprogEngelsk
TidsskriftDevelopmental Cell
Vol/bind58
Udgave nummer12
Sider (fra-til)1106-1121.e7
Antal sider24
ISSN1534-5807
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We thank Professor Kim Jensen for kindly providing R-Spondin 1- and Wnt-conditioned media for this study. We gratefully acknowledge the administrative support of Tiia M. Pelkonen. We thank Kylie Gallagher of Massachusetts Institute of Technology for assistance with medium optimization experiments. The results here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. Graphical abstract and Figures 1A, 3B, and 6A were created with BioRender.com. This work was supported by the European Union's Horizon 2020 research and innovation programme under grant agreements no. 667403 for HERCULES (O.C. K. H. J. Hynninen, S.H. A. Vähärautio, K.W.), no. 965193 for DECIDER (A. Virtanen, O.C. J. Hynninen, S.H.), and no. 845045 for RESIST3D (W.S.); Danish Cancer Society, grant no. R204-A12322 (W.S.); Novo Nordisk Foundation: Novo Nordisk Foundation Center for Stem Cell Biology, grant no NNF17CC0027852 (K.W.), High Content CRISPR Screens (HCCS) facility, grant number NNF-0061734 (K.W.); Innovation Fund Denmark and Academy of Finland for ERA PerMed JTC2020 PARIS project, grant numbers 0204-00005B (K.W.) and 344697 (A. Vähärautio), respectively; Academy of Finland, grant numbers 319243 (A. Vähärautio) and 1289059 (A. Vähärautio); the Sigrid Jusélius Foundation (A. Vähärautio); and The Cancer Foundation Finland (A. Vähärautio). Conceptualization: W.S. and K.W. Patient recruitment and management: O.C. and J. Hynninen. Patient sample processing: T.L. K.K. J. Huvila, A. Virtanen, and K.H. Organoid culture: W.S. L.G.-M, and D.B. Histological staining: A. Virtanen, M.C.K. M.K.G.H. and I.M.L. Pathologic analysis: P.C. and E.S.-R. Genomic analysis: Y.L. K.L. and J.O. Single-cell transcriptomics and analysis: M.M.F. E.P.E. J.D. A.L. A. Vähärautio. Drug response experiments and analysis: W.S. E.J.P. K.V. and Y.-J.C. Supervision: L.E. K.H. O.C. J. Hynninen, S.H. A.Vähärautio, K.W. Resources and funding acquisition: W.S. D.B. L.E. K.H. O.C. J. Hynninen, S.H. A. Vähärautio, and K.W. Writing—original draft: W.S. Writing—review and editing: W.S. L.G.-M. M.M.F. Y.L, K.L. M.C.K. J.O. D.B. E.J.P. K.V. Y.J.C. E.P.E. M.K.G.H. I.M.L. T.L. K.K. J. Huvila, A. Virtanen, L.E. P.C. E.S.-R. K.H. O.C. S.H. A. Vähärautio, and K.W. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.

Funding Information:
We thank Professor Kim Jensen for kindly providing R-Spondin 1- and Wnt-conditioned media for this study. We gratefully acknowledge the administrative support of Tiia M. Pelkonen. We thank Kylie Gallagher of Massachusetts Institute of Technology for assistance with medium optimization experiments. The results here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga . Graphical abstract and Figures 1 A, 3 B, and 6 A were created with BioRender.com . This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreements no. 667403 for HERCULES (O.C., K. H., J. Hynninen, S.H., A. Vähärautio, K.W.), no. 965193 for DECIDER (A. Virtanen, O.C., J. Hynninen, S.H.), and no. 845045 for RESIST3D (W.S.); Danish Cancer Society , grant no. R204-A12322 (W.S.); Novo Nordisk Foundation : Novo Nordisk Foundation Center for Stem Cell Biology , grant no NNF17CC0027852 (K.W.), High Content CRISPR Screens (HCCS) facility , grant number NNF-0061734 (K.W.); Innovation Fund Denmark and Academy of Finland for ERA PerMed JTC2020 PARIS project, grant numbers 0204-00005B (K.W.,) and 344697 (A. Vähärautio), respectively; Academy of Finland , grant numbers 319243 (A. Vähärautio) and 1289059 (A. Vähärautio); the Sigrid Jusélius Foundation (A. Vähärautio); and The Cancer Foundation Finland (A. Vähärautio).

Publisher Copyright:
© 2023 The Author(s)

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