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A B

C D

Figure 5. Core bone marrow microenvironment niche models constructed by the bone marrow-on-a-chip technique. (A) 3D bone marrow construct
engineering strategy (on-chip). (B) Microfluidic bone marrow microenvironment-on-chip containing osteoblastic, endothelial layers, and entire bone
marrow cells. (C) Diagrammatic representation of a five-channel polydimethylsiloxane microfluidic chip (on the left) and an enlarged depiction of the
fluidic channels (on the right). (D) The layout of the human bone marrow-on-a-chip within a 96-well plate is depicted in a 3D assembly. Images reprinted
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with permission from: (A) Sieber et al. Copyright 2017 John Wiley and Sons, Ltd; (B) Sharipol et al., licensed under CC BY 4.0; and (C and D) Nelson
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et al. Copyright 2021, Elsevier.
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Abbreviations: BMSC: Bone marrow mesenchymal stem cell; EC: Endothelial cell; HSPC: Hematopoietic stem and progenitor cell; HUVEC: Human
umbilical vein endothelial cell; MSC: Mesenchymal stem cell; OB: Osteoblast.
cell factor, CXCL12, and jagged-1) and ECM components focusing on two domains: (i) hematopoietic disorders (e.g.,
(fibronectin). Functionally, it mediated enhanced HSC leukemias) where BMOCs enable real-time observation of
maintenance with suppressed proliferation and reduced clonal evolution in a vascularized niche, and (ii) metastatic
radiation-induced apoptosis, faithfully replicating human cancers that colonize bone, where integrated fluid flow and
marrow microphysiology for high-throughput investigation 3D architecture reveal previously inaccessible dormancy-
of hematopoietic homeostasis, cancer metastasis, and inducing mechanisms. By bridging engineering precision
clinical interventions. with pathophysiological complexity, these models not only
address limitations of animal translation—such as species-
Multi-niche BMOCs represent a significant leap in
recapitulating the structural and functional complexity of specific cytokine signaling—but also establish a unique
experimental foundation to systematically dissect tumor
the human BMME. This complexity is essential for studying dormancy regulation, positioning BMOCs as indispensable
tumor dormancy, as dormant cells potentially reside in platforms for probing therapeutic resistance.
specific, protective niches.
4.1. Human-specific hematopathology modeling
4. BMOC platforms: Engineering human-
specific disease models for dormancy The bone marrow niche orchestrates HSC maintenance
insights and differentiation under physiological conditions, yet
in hematological malignancies such as acute leukemia,
The BMOCs have emerged as transformative tools malignant cells exploit this niche to promote survival
for recapitulating the dynamic interplay between and chemoresistance. While traditional 2D or 3D
hematopoietic/stromal components and disease co-culture systems provide accessible platforms for
pathologies within the human BMME. This section pathological studies, they fundamentally lack the ability
critically examines how BMOC systems advance disease to recapitulate critical in vivo niche structures—including
modeling beyond traditional approaches, specifically the central sinus, medullary cavity, and hematopoietic

Volume 1 Issue 3 (2025) 13 doi: 10.36922/OR025200017