A microfluidic bone marrow model combining CFD and organ-on-a-chip technologies to study leukemia niche dynamics

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Microfluidics

Background:

• B-cell acute lymphoblastic leukemia (B-ALL) significantly impacts bone marrow niche architecture and function.
• Existing in vitro and in vivo models inadequately replicate the complex spatial, biochemical, and mechanical aspects of the native bone marrow microenvironment.

Purpose of the Study:

• To develop a biomimetic bone marrow-on-a-chip platform that accurately reconstructs the human bone marrow microenvironment.
• To investigate niche-associated signaling in B-ALL using an advanced organ-on-a-chip system.

Main Methods:

• Integration of organ-on-a-chip technology, 3D hydrogel culture, and computational modeling (Computational Fluid Dynamics - CFD) to create distinct perivascular, central, and endosteal niches.
• Fabrication using 3D printing and soft lithography, incorporating phaseguide structures for hydrogel confinement and continuous perfusion.
• Co-culture of endothelial, stromal, osteoblast, and leukemic cells within a type I collagen matrix under dynamic conditions.

Main Results:

• The platform maintained high cell viability and supported compartmentalized spatial organization of multicellular co-cultures.
• Leukemic cells induced significant alterations in soluble signaling molecules, including increased cytokines, chemokines, and growth factors (e.g., IL-10, TNF-α, CCL2, G-CSF).
• Observed signaling patterns correlate with immunoregulation, leukemia support, and therapeutic resistance in B-ALL.

Conclusions:

• The bone-marrow-on-a-chip platform effectively captures critical niche-associated signaling relevant to B-ALL.
• This versatile system serves as a valuable tool for studying leukemia microenvironment interactions.
• The platform holds potential for drug screening and the development of preclinical models for B-ALL.