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Cancer metastasis in vitro models - can 3D biofabrication and microfluidics sow the seeds in the right soil
Yordan Sbirkov1,2, Ilian Koev3, Azad Ozanian3
1Department of Medical Biology, Medical University of Plovdiv, Plovdiv, Bulgaria.
Abstract:
More than 140 years after the first observations that cancer cells spread to secondary sites nonrandomly, the lack of representative pre-clinical models of metastasis precludes our understanding of the processes of metastasis. The development of new 3D biotechnologies, biomaterials, tissue engineering and more intricate in vitro experimental systems, however, can allow for the in-depth study of the main steps of metastasis-invasion, intravasation, circulation in the bloodstream, extravasation and colonization of new sites. In this review, we discuss the improvement of pre-clinical models with a focus on 3D biofabrication and organ-on-a-chip techniques. A systematic and critical description of the current models based on the most common sites of metastasis-the liver, the lungs, the brain and the bones is presented. The current progress in the development of the toolbox to study the mechanisms behind tumour spreading is provided. Several limitations and challenges are also highlighted with the goal to ultimately understand and prevent the major cause of cancer related deaths-metastasis. The convergence of microfluidic chip devices and bioprinting with micrometer precision, together with the implementation of biosensors measuring cellular parameters, can provide tools for the creation of vascularised multi-organ experimental systems. They reflect the complexity of human organs much more accurately than current models and can pave the way for personalised medicine and anti-metastatic drug discovery.
Insights
New 3D biofabrication and organ-on-a-chip models improve the study of cancer metastasis. These advanced pre-clinical tools help understand tumor spreading to prevent cancer deaths.
Area of Science:
- Oncology
- Biotechnology
- Biomaterials
Background:
- Cancer metastasis, the spread of cancer cells to secondary sites, remains poorly understood due to limitations in current pre-clinical models.
- Despite over 140 years of observation, a lack of representative models hinders the study of metastasis's complex processes.
Purpose of the Study:
- To review advancements in pre-clinical models for studying cancer metastasis, focusing on 3D biofabrication and organ-on-a-chip technologies.
- To critically describe current models for common metastasis sites (liver, lungs, brain, bones) and highlight progress in research tools.
- To identify limitations and challenges in metastasis research, aiming to prevent cancer-related mortality.
Main Methods:
- Review of literature on 3D biofabrication and organ-on-a-chip techniques for metastasis modeling.
- Systematic description of existing pre-clinical models for liver, lung, brain, and bone metastasis.
- Analysis of current tools for studying tumor spreading mechanisms.
Main Results:
- 3D biotechnologies, biomaterials, and tissue engineering offer intricate in vitro systems to study invasion, intravasation, circulation, extravasation, and colonization.
- Organ-on-a-chip and bioprinting technologies, combined with biosensors, enable the creation of vascularized multi-organ systems.
- These advanced systems more accurately reflect human organ complexity than traditional models.
Conclusions:
- Improved pre-clinical models, particularly those using 3D biofabrication and organ-on-a-chip, are crucial for understanding metastasis.
- The convergence of microfluidics, bioprinting, and biosensors offers powerful tools for personalized medicine and anti-metastatic drug discovery.
- Addressing limitations in current models is essential for ultimately preventing cancer deaths caused by metastasis.
