17. June 2019

Gabriele Bixel

Intravital multiphoton imaging of cellular dynamics in the bone marrow microenvironment

Max Planck Institute for Molecular Biomedicine/ Muenster, Germany

The bone marrow is located within the bone marrow cavities of long and flat bones. It forms an unique and highly dynamic microenvironment and is the principle site of postnatal hematopoiesis controlling the maintenance and self-renewal of hematopoietic stem cells. The bone marrow microvasculature forms a dense and irregular network of interconnecting sinusoidal microvessels specialized in transporting various cell types entering and exiting the bone marrow. 

Due to technical challenges associated with in vivo high-resolution imaging in the intact bone, the cellular dynamics in the bone marrow microenvironment and the impact of blood flow on cell trafficking in the various types of bone marrow microvessels have remained poorly understood.

We developed an intravital multiphoton imaging approach to visualize the cellular dynamics in the bone marrow microenvironment using a chronic cranial window in the mouse. We obtained a detailed flow map of the bone marrow microvasculature with hemodynamic parameters by capturing the motion of red blood cells. Arterioles branching from larger arteries were found to control the blood flow into the bone marrow compartment. As predicted, flow rates decreased considerably in downstream sinusoidal capillaries with wider vessel diameters. Most interestingly, we observed highly variable flow rates among sinusoidal capillaries with some microvessels showing barely any flow possibly affecting local oxygen tension.

Next we analyzed the impact of blood flow on the homing behavior of hematopoietic stem and progenitor cells (HSPCs) to the bone marrow. We observed considerable variability in HSPC rolling and adhesion in irregularly shaped sinusoidal capillaries, while no homing events were detected in arterial vessels. HSPCs prefer sinusoids with slow blood flow and low shear stress as sites for homing to the bone marrow compartment.

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