Organoid culture system for patient-derived lung metastatic osteosarcoma
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ORIGINAL PAPER
Organoid culture system for patient‑derived lung metastatic osteosarcoma Aina He1,2 · Yujing Huang1 · Wanying Cheng3 · Deng Zhang3 · Weiwei He4 · Yueqing Bai5 · Chao Gu5 · Zhongping Ma6 · Zhenfang He6 · Guifan Si6 · Bing Chen6 · David T. Breault7 · Min Dong2 · Dongxi Xiang8,9 Received: 10 April 2020 / Accepted: 9 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Osteosarcoma (OS) is the most common primary bone malignancy with high rates of recurrence and metastasis. OS often spreads to lungs, an optimized model for studying lung metastatic OS cells may help develop potential therapies for patients with lung metastasis. Here we firstly report an organoid culture system for lung metastatic OS tissues. We provided a fully described formula that was required for establishing lung metastatic OS organoids (OSOs). Using this protocol, the lung OSOs were able to be maintained and serially propagated for at least six months; the OSOs can also be generated from cryopreserved patient samples without damaging the morphology. The patient-derived lung OSOs retained the cellular morphology and expression of OS markers (Vimentin and Sox9) that recapitulate the histological features of the human OS. The microenvironment of primary lung metastatic OSOs preserved a similar T cell distribution with the human lung OS lesions; this provided a possible condition to explore how OS cells may react to immunotherapy. OSOs established from this protocol can be further utilized for studying various aspects of OS biology (e.g., tumorigenesis and drug screen/discovery) for precision medicine. Keywords Osteosarcoma · Organoid culture · Immunotherapy · PD-1 Abbreviations OS Osteosarcoma OSOs OS organoids PDXs Patient-derived xenograft models ECM Extracellular matrix EGF Epidermal growth factor Aina He and Yujing Huang have contributed equally to the work. * Aina He [email protected] * Dongxi Xiang [email protected]; [email protected] 1
Department of Oncology, Shanghai Jiaotong University, Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China
2
Department of Urology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
3
Shanghai Bioheb Biomed Technology Company, Shanghai, People’s Republic of China
4
Department of Thoracic Surgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China
Rspo1 R-spondin 1 RBC Red blood cell FBS Fetal bovine serum PBS Phosphate buffer saline IHC Immunohistochemistry TME Tumor microenvironment FACS Fluorescence-activated cell sorting TILs Tumor-infiltrating lymphocytes 5
Department of Pathology, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China
6
Shanghai OneTar Biomedicine, Shanghai, People’s Republic of China
7
Division of Endocrinology, Boston Children’s Hospital, Boston, MA 02115, USA
8
State Key Laboratory of Oncogenes and Related Genes, Shanghai Research Center of Bili
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