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Updated: Jan 10, 2026
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Pulsed electromagnetic field stimulation subtly modulates doxorubicin sensitivity in a spheroid co-culture model of
Ksenia Menshikh1, Myriam Antonaci1, Valentina Radini1
1Center for Translational Research on Autoimmune and Allergic Diseases- CAAD, Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy.
Abstract:
Osteosarcoma is a rare but aggressive bone cancer primarily affecting children and adolescents. Current treatment options are limited by toxicity and reduced efficacy in advanced stages. Pulsed electromagnetic field (PEMF) stimulation has shown promise as a non-invasive anticancer strategy, though inconsistent experimental models and exposure protocols limit translational progress. In the present study, a co-culture spheroid model of osteosarcoma was optimized using human osteosarcoma U2OS cells and bone marrow-derived mesenchymal stem cells (hBMSCs) and used to investigate whether PEMF exposure (1.5 mT, 75 Hz, sinusoidal) enhances spheroid sensitivity to doxorubicin (DOX). The model was characterized by structural integrity, mechanical properties, and functionality: while U2OS monoculture spheroids lacked structural stability, 1:3 MSC-U2OS co-cultures produced compact, stiff spheroids with migratory potential. PEMF stimulation for 3 days at 4 h per day reduced cell metabolic activity and spheroid stiffness and caused the downregulation of several genes associated with proliferation, survival, and invasion. These changes were most evident when combined with low-dose DOX, suggesting altered sensitivity; however, the effect was not uniformly detectable across all assessment methods. Thus, PEMF stimulation induces biological changes consistent with increased chemosensitivity in a subset of conditions, though the effect is subtle and assay-dependent. The developed co-culture model offers a relevant platform for further investigation of PEMF as a modulator of anticancer treatment response.
Insights
Pulsed electromagnetic field (PEMF) stimulation may enhance osteosarcoma (bone cancer) sensitivity to doxorubicin. This study developed a novel co-culture model to investigate PEMF
Area of Science:
- Oncology
- Biophysics
- Biomaterials
Background:
- Osteosarcoma is an aggressive bone cancer with limited treatment options.
- Pulsed electromagnetic field (PEMF) stimulation shows potential as a non-invasive cancer therapy.
- Inconsistent models hinder PEMF's translation to clinical osteosarcoma treatment.
Purpose of the Study:
- To optimize a co-culture spheroid model for osteosarcoma.
- To investigate PEMF's effect on osteosarcoma spheroid sensitivity to doxorubicin (DOX).
- To assess PEMF's impact on spheroid structure, mechanics, and gene expression.
Main Methods:
- Developed and characterized a 3D co-culture spheroid model using U2OS cells and hBMSCs.
- Applied sinusoidal PEMF (1.5 mT, 75 Hz) for 3 days (4 h/day).
- Assessed spheroid structural integrity, mechanical properties, metabolic activity, and gene expression, with and without DOX.
Main Results:
- Optimized co-cultures formed stable, stiff spheroids with migratory potential.
- PEMF stimulation reduced spheroid metabolic activity, stiffness, and downregulated key genes.
- PEMF combined with low-dose DOX showed subtle, assay-dependent increases in chemosensitivity.
Conclusions:
- The developed co-culture model is a relevant platform for studying osteosarcoma.
- PEMF induces biological changes suggesting potential for enhanced doxorubicin efficacy.
- Further research is needed to optimize PEMF protocols and validate findings across assays.
