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Updated: Jun 8, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Advancing osteosarcoma 3D modeling in vitro for novel tumor microenvironment-targeted therapies development
Sofia Costa1, João Rodrigues2, Carolina Vieira3
1i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Abstract:
Osteosarcoma (OS) represents one of the most common primary bone cancers affecting children and young adults. The available treatments have remained unimproved for the past decades, hampered by the poor knowledge of OS etiology/pathophysiology and the lack of innovative, predictive and biologically relevant in vitro models, that can recapitulate the 3D OS tumor microenvironment (TME). Here, we report the development and characterization of an innovative 3D model of OS, composed of OS tumor cells, immune cells (macrophages) and mesenchymal stem cells (MSCs), that formed a multicellular tissue spheroid (MCTS). This fully humanized 3D model was shown to accurately mimic the native histological features of OS, while innately leading to the polarization of macrophages towards an M2-like phenotype, highly aggressive and pro-tumor profile. Upon the exposure to immunomodulatory molecules, the MCTS were shown to be responsive by shifting macrophages polarization, and dramatically altering the TME secretome. In agreement, when treated with immunomodulatory/stimulatory nanoparticles (NPSs), we were able to revert the TME secretome towards an anti-inflammatory profile. This study establishes an advanced 3D OS model capable of shedding light on macrophages and MSCs contributions to disease progression, paving the way for the development of innovative therapeutic approaches targeting the OS TME, while providing a biologically relevant in vitro tool for the efficacy screening of novel OS therapeutic approaches.
Insights
A new 3D osteosarcoma (OS) model using tumor cells, macrophages, and mesenchymal stem cells (MSCs) mimics the tumor microenvironment (TME). This model aids in developing targeted therapies for OS by testing nanoparticle efficacy.
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.
