Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells’ Escape from the Bone Marrow Microenvironment

Author:

Verbruggen Stefaan W.123ORCID,Freeman Ciara L.4,Freeman Fiona E.56789ORCID

Affiliation:

1. Digital Environment Research Institute, Queen Mary University of London, London E1 4NS, UK

2. Center for Predictive In Vitro Models, School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK

3. INSIGNEO Institute for In Silico Medicine, University of Sheffield, Sheffield S1 3JD, UK

4. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA

5. School of Mechanical and Materials Engineering, Engineering and Materials Science Centre, University College Dublin, D04 V1W8 Dublin, Ireland

6. Conway Institute of Biomolecular and Biomedical Research, University College Dublin, D04 V1W8 Dublin, Ireland

7. Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland

8. Department of Mechanical Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, D02 PN40 Dublin, Ireland

9. Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, D02 YN77 Dublin, Ireland

Abstract

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments. To build upon these advances, it is crucial to develop models of MM evolution, particularly focusing on understanding the biological mechanisms behind its development outside the bone marrow. This comprehensive understanding is essential to devising innovative treatment strategies. This review emphasizes the role of 3D models, specifically addressing the bone marrow microenvironment and development of extramedullary sites. It explores the current state-of-the-art in MM modelling, highlighting challenges in replicating the disease’s complexity. Recognizing the unique demand for accurate models, the discussion underscores the potential impact of these advanced 3D models on understanding and combating this heterogeneous and still incurable disease.

Funder

U.K. Engineering and Physical Sciences Research Council

Publisher

MDPI AG

Reference98 articles.

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