A Humanized Bone Metastasis Model: Ex Vivo and In Vivo Applications

Abstract

Patients with breast or prostate cancer have a high chance of developing bone metastasis, which is associated with many skeletal-related events. The development of novel bone metastasis treatments is lagging behind due to the lack of reliable models. We aimed to develop a humanized bone metastasis model comprising vital human bone discs and human metastatic cancer cells (bone metastasis discs), which were subsequently cultured ex vivo or subcutaneously implanted into nude mice. Ex vivo culture experiments confirmed that cells within the bone metastasis discs remained metabolically active, while the presence of metastatic cancer cells could be monitored using bioluminescence. Although histological analyses confirmed the presence of relevant bone cells in the human bone tissue, no apparent formation of metastatic lesions was detected over the 2-week ex vivo culture period. In contrast, subcutaneously implanted bone metastasis discs demonstrated clear metastatic lesion formation, with osteolytic characteristics, that progressed from 3 to 6 weeks after implantation for both breast and prostate cancer bone metastasis discs. Histologically, healthy bone tissue with bone marrow compartments as well as anastomosis was observed. Cisplatin treatment of ex vivo cultured bone metastasis discs significantly decreased the bioluminescent signal from (prostate) cancer cells, while no effects of cisplatin treatment were observed for in vivo implanted bone metastasis discs. Our data provide a proof of concept for an ex vivo/in vivo bone metastasis model with vital human bone and human metastatic cancer cells but require further fine-tuning to improve robustness, relevance, and quantification methods. Future research could potentially use these models for the evaluation of novel bone metastasis treatments, accelerating their potential clinical application.

Impact Statement

Bone metastasis remains a major clinical challenge in breast and prostate cancer, in part due to the lack of physiologically relevant human-based experimental models for therapy development. This study presents a proof-of-concept humanized bone metastasis platform that integrates vital human bone tissue with human metastatic cancer cells in both ex vivo and in vivo settings. By demonstrating sustained tissue viability, tumor cell monitoring, and clinically relevant osteolytic lesion formation in vivo, this work advances current bone metastasis modeling beyond conventional animal and in vitro systems. Although further optimization is required, this dual ex vivo/in vivo approach provides a promising foundation for more predictive preclinical testing of bone-targeted anticancer therapies, with potential to accelerate translation toward clinical application.