Cocchi Claudia, Dapporto Massimiliano, Guerrieri Ania Naila, Liverani Chiara, Tavoni Marta, Bellotti Chiara, Spadazzi Chiara, Tampieri Anna, Gambarotti Marco, Miserocchi Giacomo, Sprio Simone, Lucarelli Enrico, Iafisco Michele, Ibrahim Toni, De Vita Alessandro, Mercatali Laura
Preclinic and Osteoncology Unit, Bioscience Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Via P. Maroncelli 40, 47014 Meldola, Italy.
Institute of Science, Technology and Sustainability for Ceramics (ISSMC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy.
J Funct Biomater. 2025 Jun 12;16(6):220. doi: 10.3390/jfb16060220.
Breast cancer (BC) frequently metastasizes to bone, leading to poor patient prognosis. The infiltration of cancer cells in bone impairs its homeostasis, triggering a pathological interaction between tumors and resident cells. Preclinical models able to mimic the bone microenvironment are needed to advance translational findings on BC mechanisms and treatments. We designed strontium-doped calcium phosphate cement to be employed for culturing cancer and bone cells and developed an in vitro bone metastasis model. The platform was established step by step, starting with the monoculture of cancer cells, mature osteoblasts (OBs) differentiated from mesenchymal stem cells, and mature osteoclasts (OCs) differentiated from Peripheral Blood Mononuclear Cells. The model was implemented with the co-culture of cancer cells with OBs or OCs, or the co-culture of OBs and OCs, allowing us to discriminate the interaction between the actors of the bone metastatic niche. The biomimetic material was further challenged with bone metastasis patient-derived material, showing good versatility and biocompatibility, suggesting its potential use as bone substitute. Overall, we developed a bone-mimicking model able to reproduce reciprocal interactions between cancer and bone cells in a biomimetic environment suitable for studying the biomolecular determinants of bone metastasis and, in the future, as a drug efficacy platform.
乳腺癌（BC）常转移至骨骼，导致患者预后不良。癌细胞在骨中的浸润会破坏其稳态，引发肿瘤与驻留细胞之间的病理相互作用。需要能够模拟骨微环境的临床前模型来推进关于BC机制和治疗的转化研究结果。我们设计了掺锶磷酸钙骨水泥用于培养癌细胞和骨细胞，并开发了一种体外骨转移模型。该平台是逐步建立的，首先是癌细胞、从间充质干细胞分化而来的成熟成骨细胞（OBs）以及从外周血单核细胞分化而来的成熟破骨细胞（OCs）的单培养。该模型通过癌细胞与OBs或OCs的共培养，或OBs和OCs的共培养来实现，使我们能够区分骨转移微环境中各参与者之间的相互作用。这种仿生材料进一步用骨转移患者来源的材料进行测试，显示出良好的通用性和生物相容性，表明其作为骨替代物的潜在用途。总体而言，我们开发了一种模拟骨的模型，能够在适合研究骨转移生物分子决定因素的仿生环境中重现癌细胞与骨细胞之间的相互作用，并且在未来可作为药物疗效平台。
