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

Senkowski, W.; Gall-Mas, L.; Falco, M. M.; Li, Y.; Lavikka, K.; Kriegbaum, M. C.; Oikkonen, J.; Bulanova, D.; Pietras, E. J.; Vossgröne, K.; Chen, Y.-J.; Erkan, E. P.; Gronning Hog, M. K.; Larsen, I. M.; Lamminen, T.; Kaipio, K.; Huvila, J.; Virtanen, A.; Engelholm, L. H.; Christiansen, P.; Santoni-Rugiu, E.; Huhtinen, K.; Carpen, O.; Hynninen, J.; Hautaniemi, S.; Vähärautio, A.; Wennerberg, K.

doi:10.1101/2022.04.21.489027

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bioRxiv · 10.1101/2022.04.21.489027

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

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Abstract

The broad research use of organoids from high-grade serous ovarian carcinoma (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 (55% 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 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 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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Senkowski, W., Gall-Mas, L., Falco, M. M., Li, Y., Lavikka, K., Kriegbaum, M. C., Oikkonen, J., Bulanova, D., Pietras, E. J., Vossgröne, K., Chen, Y.-J., Erkan, E. P., Gronning Hog, M. K., Larsen, I. M., Lamminen, T., Kaipio, K., Huvila, J., Virtanen, A., Engelholm, L. H., Christiansen, P., Santoni-Rugiu, E., Huhtinen, K., Carpen, O., Hynninen, J., Hautaniemi, S., Vähärautio, A., Wennerberg, K.. 2022-04-21. A platform for efficient establishment, expansion and drug response profiling of high-grade serous ovarian cancer organoids. https://doi.org/10.1101/2022.04.21.489027

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