Investigation of human bone tumours in a mouse model with a human tissue-engineered bone niche

Malignant primary bone tumours, such as osteosarcoma, Ewing-Sarcoma and chondrosarcoma, often occur in adolescents and young adults and are associated with substantial health burdens for individual patients. Recurrence and metastasis in particular are associated with poor survival prognoses. To improve the treatment of these rare diseases in the future, innovative preclinical models are needed to better understand the patient-specific and entity-specific pathomechanisms and conduct future drug trials on a personalized level. The development of cutting-edge personalized preclinical models, particularly those that incorporate patient-derived tissue and address the bone microenvironment, is a promising strategy to make research more relevant to actual patient conditions and help bridge the gap to successful clinical applications. However, there remains a lack of models incorporating both a (human) bone microenvironment and a patient-specific tumour component. Therefore, the aim of our study is to establish a patient-specific mouse model for malignant primary bone tumours with a humanized bone nische to enhance the understanding of these rare diseases and to support more effective drug testing in the future. To achieve the mouse model, first patient-derived tumour tissue is combined with a tissue-engineered bone construct and pre-cultured in vitro. The tissue-engineered bone construct consists of osteoprogenitor cells seeded onto calcium phosphate coated 3D-printed mPCL scaffolds. The tumour tissue is subsequently placed on top and fixed using fibrin glue for co-culture. After in vitro culture, the co-constructs are implanted subcutaneously into the back of severely immunodeficient NXG mice for 12 weeks to allow for in vivo bone formation, tumour growth, as well as sufficient time for tissue interaction. Subsequently, ex vivo analysis of the tumor-bone interface will be carried out using micro-computed tomography, immunohistochemistry as well as gene expression analysis.