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compartments—limiting mechanistic insights into disease leukemia niches, enabling real-time observation of
progression. 81,82 To overcome these constraints, BMOCs dynamic cell–ECM interactions. Comparative analysis
offer a transformative approach for reconstructing the with in vivo murine models revealed that the chip
leukemic BMME, enabling precise dissection of niche recapitulates leukemic spatial organization and identifies
interactions and chemoresistance pathways. 83-86 For subtype-specific mechanisms: for example, perivascular
example, Ma et al. developed an innovative “leukemia- and hematopoietic niche-derived signals (e.g., CXCL12
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on-a-chip” model to emulate the BMME and dissect cytokines and vascular cell adhesion protein 1/osteopontin
spatial-genetic heterogeneity in regulating chemotherapy adhesion molecules) promote B-ALL quiescence through
resistance across diverse B-cell acute lymphoblastic NF-κB pathway activation, elucidating heterogeneous
leukemia (B-ALL) subtypes (Figure 6A). Unlike traditional chemoresistance in patient-derived samples. Crucially, this
in vitro co-culture systems, which fail to replicate key model advances preclinical applications by demonstrating
niche structures such as the central sinus and endosteal niche-cotargeting therapies for personalized screening,
regions, this BMOC platform integrates microfluidic addressing translational gaps not captured in animal
channels and hydrogels to accurately mimic vascularized systems.

A C

B E

D

Figure 6. BMOC platforms for modeling human-specific bone marrow pathologies and metastatic niches. (A) Leukemia-on-a-chip architectural
schematic featuring three functionalized compartments. (B) The bone marrow-on-a-chip (center) was seeded with human bone marrow-derived cells
(right) to emulate the physiological environment found in vivo (left). (C) Comparative cluster of differentiation 34-positive (CD34 ) hematopoietic cell
+
culturing in bone marrow chips: Healthy donors versus Shwachman-Diamond syndrome patients (2-week culture). (D) Schematic diagram of the design
and construction of self-mineralizing bone-on-a-chip. (E) Design and application of a pre-metastatic niche-mimicking bone-on-a-chip platform. Images
reprinted with permission from: (A) Ma et al., licensed under CC BY-NC 4.0; (B) Ma et al., licensed under CC BY 4.0; (C) Chou et al. Copyright
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2020, Springer Nature; (D) Hao et al. Copyright 2018, Wiley-VCH; and (E) Ji et al. Copyright 2023, Wiley-VCH.
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Abbreviations: B-ALL: B-cell acute lymphoblastic leukemia; CAR-T: Chimeric antigen receptor T-cell; EC: Endothelial cell; ECM: Extracellular matrix;
GelMA: Gelatin methacrylate; HSPC: Hematopoietic stem and progenitor cell; HUVEC: Human umbilical vein epithelial cell; MSC: Mesenchymal
stem cell.
Volume 1 Issue 3 (2025) 14 doi: 10.36922/OR025200017