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Review

Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers

by
Kathryn A. Skelding
1,2,*,
Daniel L. Barry
1,2 and
Lisa F. Lincz
1,2,3
1
Cancer Cell Biology Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW 2308, Australia
2
Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
3
Hunter Haematology Research Group, Calvary Mater Hospital Newcastle, Waratah, NSW 2298, Australia
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(15), 2571; https://doi.org/10.3390/cancers17152571
Submission received: 23 June 2025 / Accepted: 1 August 2025 / Published: 4 August 2025
(This article belongs to the Section Tumor Microenvironment)

Simple Summary

Relapse and treatment resistance remain a major concern for hematological malignancies. Despite treatment advancements, many patients still have poor long-term outcomes. This is partly because current preclinical models do not always accurately mimic the in vivo environment. Herein, we review recent advancements in using 3D in vitro models to study hematological malignancies, focusing on models that better reflect human physiological conditions. Improved models could lead to better-informed research and, ultimately, more effective treatment for patients.

Abstract

Despite significant advancements in understanding the pathogenesis and treatment of hematological malignancies, including leukemia and multiple myeloma, the majority of patients continue to experience poor long-term outcomes. This is partly due to the difficulty of accurately recapitulating the malignant microenvironment in vitro, particularly the bone marrow niche. The complexity of the bone marrow microenvironment poses a challenge for the in vitro examination of hematological malignancies. Traditionally, 2D culture and animal models have been utilized, but these representations are limited and have been criticized for their lack of human physiological relevance. In an attempt to overcome this, 3D models have been developed that more accurately recapitulate the in vivo microenvironment. Herein, we present an overview of recent developments in 2D and 3D models used for studying the bone marrow niche in hematological malignancies, highlighting their advantages and limitations.
Keywords: bone marrow microenvironment; hematological cancers; hematological malignancies; co-culture; stromal cells; spheroids; bioreactors bone marrow microenvironment; hematological cancers; hematological malignancies; co-culture; stromal cells; spheroids; bioreactors

Share and Cite

MDPI and ACS Style

Skelding, K.A.; Barry, D.L.; Lincz, L.F. Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers. Cancers 2025, 17, 2571. https://doi.org/10.3390/cancers17152571

AMA Style

Skelding KA, Barry DL, Lincz LF. Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers. Cancers. 2025; 17(15):2571. https://doi.org/10.3390/cancers17152571

Chicago/Turabian Style

Skelding, Kathryn A., Daniel L. Barry, and Lisa F. Lincz. 2025. "Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers" Cancers 17, no. 15: 2571. https://doi.org/10.3390/cancers17152571

APA Style

Skelding, K. A., Barry, D. L., & Lincz, L. F. (2025). Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers. Cancers, 17(15), 2571. https://doi.org/10.3390/cancers17152571

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