In vitro microfluidic model for the study of vaso-occlusive processes

Area of Science:

• Biomedical Engineering
• Hematology
• Microfluidics

Background:

• Vaso-occlusion is a primary cause of morbidity in sickle-cell disease (SCD), driven by leukocyte adhesion in the microcirculation.
• Understanding cellular interactions within the microvasculature is crucial for developing effective SCD therapies.

Purpose of the Study:

• To develop and utilize a microfluidic biochip that mimics the microcirculation.
• To investigate the role of neutrophils and red blood cells from individuals with SCD in vaso-occlusive processes.

Main Methods:

• A microfluidic biochip with microchannels (40 μm to 10 μm) was used to simulate blood flow.
• The adhesion and obstruction dynamics of neutrophils and red blood cells from healthy and SCD individuals were observed under physiological flow conditions.
• Microchannels were coated with laminin or endothelial adhesion molecules (E-selectin/ICAM-1).

Main Results:

• Sickle-cell anemia (SCA) neutrophils caused significantly greater obstruction in E-selectin/ICAM-1 coated microchannels compared to healthy neutrophils, especially in 40-15 μm channels.
• SCA red blood cells alone did not cause significant obstruction.
• Mixed suspensions of SCA neutrophils and red blood cells significantly adhered to and obstructed laminin-coated channels.

Conclusions:

• Leukocytes, particularly neutrophils, play a primary role in initiating vaso-occlusive events in the microcirculation of SCD.
• This in vitro microfluidic assay provides a reproducible method to study cellular interactions in microvasculature-like channels.
• The assay has potential for evaluating drugs targeting occlusive mechanisms in SCD and other thrombotic diseases.