Imaging the Vascular Bone Marrow Niche During Inflammatory Stress

Area of Science:

• Hematology
• Immunology
• Vascular Biology
• Medical Imaging

Background:

• Bacterial lipopolysaccharide induces inflammatory stress, leading to hematopoietic stem cell expansion in the bone marrow niche.
• The bone marrow vasculature is crucial for regulating leukocyte production and release, impacting host defense and inflammatory diseases.

Purpose of the Study:

• To develop novel imaging tools for exploring bone marrow vascular adaptations during acute inflammation.

Main Methods:

• Multiparametric, multimodality, and multiscale imaging techniques were employed.
• Characterization involved ex vivo flow cytometry, histology, intravital microscopy, and positron emission tomography/magnetic resonance imaging.
• Vascular changes were assessed using integrin αVβ3 imaging and quantification of vascular leakiness.

Main Results:

• Lipopolysaccharide challenge induced significant vascular remodeling in the bone marrow niche.
• Proliferating endothelial cells contributed to new vasculature formation under hypoxic conditions.
• Increased vascular leakiness correlated with neutrophil egress and enhanced hematopoietic stem and progenitor cell proliferation.

Conclusions:

• A novel imaging toolkit provides cellular resolution and whole-skeleton noninvasive views of bone marrow vasculature.
• These findings illuminate angiogenic responses during emergency hematopoiesis.
• Monitoring bone marrow vasculature presents potential therapeutic targets for systemic inflammation.