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REVIEW ARTICLE
Bone marrow microenvironment and organ

chips: Advances in tumor dormancy research

Renshan Li 1† , Jiaqi Zhou 2† , Man Shu 2 , Guoqing Zhong 2 , Jin Ke * , Zhidao Xia * , and Xiongfa Ji *
1
3
2
1 Department of Orthopaedics, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong, China
2 Department of Orthopaedics Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern
Medical University, Guangzhou, Guangdong, China
3 Institute of Life Science, Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, United Kingdom
*Corresponding authors: Jin Ke (kejin332500@163.com); Zhidao Xia (z.xia@swansea.ac.uk); Xiongfa Ji (jixiongfa@126.com)

† These authors contributed equally to Abstract
this work.
Citation: Li R, Zhou J, Shu M, Bone metastasis presents a major challenge in oncology, often involving prolonged
et al. Bone marrow microenvironment tumor dormancy within the complex bone marrow microenvironment (BMME).
and organ chips: Advances in tumor This dormancy, characterized by halted proliferation but sustained viability, poses
dormancy research. Organoid Res.
2025;1(3):025200017. risks for late recurrence and therapy resistance. Recent advancements in bone
doi: 10.36922/OR025200017 marrow-on-a-chip (BMOC) technology provide highly controllable, physiologically
Received: May 14, 2025 relevant biomimetic platforms to model the intricate cellular and molecular
interactions governing BMME-regulated dormancy. This review focuses on BMOC-
1st revised: August 04, 2025 based approaches, examining their principles, distinct advantages, applications, and
2nd revised: August 19, 2025 key findings in elucidating mechanisms of tumor dormancy regulation. Critically, it
Accepted: August 22, 2025 addresses current technical and biological limitations of BMOCs (e.g., replicating
full immune component complexity) and propose concrete future directions for
Published online: September 8,
2025 enhancing BMOC development and integration with complementary technologies.
Enhanced understanding through refined BMOC technology could fundamentally
Copyright: © 2025 Author(s). This uncover dormancy mechanisms and advance novel therapeutic strategies for
is an Open-Access article distributed
under the terms of the Creative metastatic control.
Commons Attribution License,
permitting distribution, and reproduction
in any medium, which provided that the Keywords: Bone marrow microenvironment; Organ-on-a-chip; Microfluidics; Tumor
original work is properly cited. dormancy; Organoid
Publisher’s Note: AccScience
Publishing remains neutral with regard
to jurisdictional claims in published
maps and institutional affiliations.

1. Introduction through complex interactions involving stromal, immune,
and cytokine networks. Traditional murine models face
5,6
Cancer remains a leading cause of global mortality, substantial limitations in capturing the dynamic interplay
with metastases driving advanced disease progression. and multicellular complexity of the human BMME. Key
1,2
7
Bone, a frequent metastatic site, poses significant clinical challenges include difficulties in real-time monitoring,
challenges due to debilitating skeletal complications a lack of precise microenvironmental manipulation,
and the elusive nature of tumor dormancy. During this and ethical/practical constraints highlighted by recent
3
clinically silent phase, disseminated tumor cells (DTCs) regulatory shifts, such as the FDA Modernization Act 2.0.
8
enter a state of mitotic arrest and metabolic quiescence, These shortcomings underscore the need for alternative,
evading detection and exhibiting resistance to conventional human-relevant models.
therapies. Crucially, the bone marrow microenvironment Bone marrow-on-a-chip (BMOC) technology emerges
4
(BMME) governs this dormancy–reactivation balance as a transformative solution. By integrating patient-

Volume 1 Issue 3 (2025) 1 doi: 10.36922/OR025200017