"Humanized Mice Models for Primary Bone Tumor and Bone Metastasis Research"

Dietmar Hutmacher, Ph.D.
Professor
Chemistry, Physics, Mechanical Engineering,
Biomedical Engineering and Medical Physics
Queensland University of Technology

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human”. To get answers to questions that would be prognostic of outcomes in human medicine, the mouse’s genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumour development and progression. However, the translational benefits of these platforms have still to be proven.

Bone is a site prone to the development of different tumors and a preferred site for hematogenous metastasis from solid tumors such as breast, prostate or lung cancer. Studying the bone microenvironment and its malignancies is challenging as it hosts the interplay of numerous cellular and extracellular components, and its location and structure render it difficult to access and investigate. Over the last decade, major research efforts have focused on developing alternative models to study physiological and pathological processes within the bone microenvironment. Bioengineered tissues generated subcutaneously in immunodeficient mice have proven advantageous in terms of the ease of surgical procedure, accessibility for live imaging and monitoring, and design flexibility, which allows interrogating the contribution of different tissue components to tumor development or metastatic invasion. The talk provides an overview of the state of the art of humanized mice models and highlights future developments in the field such as the application of tissue engineering & regenerative medicine (TE&RM) strategies to further enhance humanized murine model systems.