Advancing osteosarcoma 3D modeling in vitro for novel tumor microenvironment-targeted therapies development

Area of Science:

• Oncology
• Biomedical Engineering
• Immunology

Background:

• Osteosarcoma (OS) is a prevalent bone cancer in young individuals with limited treatment advancements.
• Existing in vitro models lack the complexity to replicate the 3D osteosarcoma tumor microenvironment (TME).
• Understanding OS pathophysiology and developing predictive models are crucial for therapeutic innovation.

Purpose of the Study:

• To develop and characterize an innovative 3D multicellular tissue spheroid (MCTS) model of osteosarcoma.
• To investigate the role of macrophages and mesenchymal stem cells (MSCs) within the OS TME.
• To establish a biologically relevant in vitro platform for screening novel therapeutic strategies.

Main Methods:

• Construction of a fully humanized 3D OS model comprising OS cells, macrophages, and MSCs.
• Assessment of the model's histological mimicry of native OS and macrophage polarization.
• Evaluation of MCTS response to immunomodulatory molecules and nanoparticles (NPSs).

Main Results:

• The 3D OS model accurately recapitulated histological features and promoted M2-like macrophage polarization.
• The model demonstrated responsiveness to immunomodulatory agents, altering TME secretome profiles.
• Treatment with nanoparticles reverted the TME secretome towards an anti-inflammatory state.

Conclusions:

• The developed 3D OS model provides insights into macrophage and MSC contributions to tumor progression.
• This advanced model serves as a valuable tool for evaluating therapeutic approaches targeting the OS TME.
• The study paves the way for developing innovative treatments for osteosarcoma.