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Published on: July 17, 2013
A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing Sarcoma
Maria Vittoria Colombo1, Chiara Arrigoni2, Tobias Faehling3
1Regenerative Medicine Division, Institute for Translational Research, Ente Ospedaliero Cantonale - Università della Svizzera Italiana, via F Chiesa 5, Bellinzona 6500, Switzerland; Department of Chemistry, Materials and Chemical Engineering G.Natta, Politecnico di Milano, Piazzale Leonardo da Vinci 32, Milan 20100, Italy.
A new microphysiological system mimics endochondral ossification (bone development) to study Ewing Sarcoma (EwS). Hypertrophic conditions in this model promote EwS cell growth and migration, offering insights into tumor progression.
Area of Science:
- Biomedical Engineering
- Developmental Biology
- Oncology
Background:
- Endochondral ossification (ECO) is crucial for long bone development in children.
- Disruptions in bone development pathways are linked to pediatric bone cancers like Ewing Sarcoma (EwS).
- Existing preclinical models for EwS have limitations.
Purpose of the Study:
- To develop a microphysiological system that mimics ECO stages.
- To investigate the influence of ECO stages on EwS cell proliferation and migration.
- To establish a novel preclinical model for EwS research.
Main Methods:
- Constructed a microphysiological system using mesenchymal stromal cell spheroids in fibrin hydrogels.
- Differentiated cells through chondrogenic and hypertrophic stages, with and without vascular cells and mineralized particles.
- Assessed EwS cell proliferation and migratory behavior within the system.
Main Results:
- Successfully recapitulated hypertrophic ECO stages, enhanced by vascular cells.
- Hypertrophic conditions significantly increased EwS cell proliferation compared to other environments.
- Supported migration of aggressive EWSR1::FLI1 low EwS cells, unlike control gels.
Conclusions:
- The ECO-mimicking microphysiological system is a valuable preclinical model.
- This system can elucidate the role of developmental processes in EwS.
- Findings provide new avenues for understanding and potentially treating EwS.
