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

Wojciech Senkowski(University of Copenhagen), Laura Gall-Mas(University of Copenhagen), Matías Marín Falco(University of Helsinki), Yilin Li(University of Helsinki), Kari Lavikka(University of Helsinki), Mette C. Kriegbaum(University of Copenhagen), Jaana Oikkonen(University of Helsinki), Daria Bulanova(University of Copenhagen), Elin J. Pietras(University of Copenhagen), Karolin Voßgröne(University of Copenhagen), Yan-Jun Chen(University of Copenhagen), Erdoğan Pekcan Erkan(University of Helsinki), Jun Dai(University of Helsinki), Anastasia Lundgren(University of Helsinki), Mia Kristine Grønning Høg(University of Copenhagen), Ida Marie Larsen(University of Copenhagen), Tarja Lamminen(University of Turku), Katja Kaipio(University of Turku), Jutta Huvila(University of Turku), Anni Virtanen(University of Helsinki), Lars H. Engelholm(University of Copenhagen), P. Christiansen(Copenhagen University Hospital), Eric Santoni‐Rugiu(Copenhagen University Hospital), Kaisa Huhtinen(University of Helsinki), Olli Carpén(University of Helsinki), Johanna Hynninen(University of Turku), Sampsa Hautaniemi(University of Helsinki), Anna Vähärautio(University of Helsinki), Krister Wennerberg(University of Copenhagen)
Developmental Cell
May 5, 2023
Cited by 112Open Access
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Abstract

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.


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