[Microcirculation] Microfluidics for Investigating Vaso-Occlusions in Sickle Cell Disease
Sickle Cell Disease (SCD) stems from a mutation in the beta globin gene. Upon deoxygenation, hemoglobin polymerizes and triggers red blood cell remodeling. This phenomenon is central to SCD pathogenesis as individuals suffering from the disease are plagued by painful vaso-occlusive crises episodes. These episodes are the result of a combination of processes including inflammation, thrombosis, and blood cell adhesion to the vascular wall which leads to blockages within the vasculature termed vaso-occlusions. Vaso-occlusive episodes deprive tissues of oxygen and are a major contributor to SCD-related complications, unfortunately the complex mechanisms that contribute to vaso-occlusions are not well understood. Vaso- occlusions can occur in post-capillary venules; hence, the microvasculature is a prime target for SCD therapies. Traditional in vitro systems poorly recapitulate architectural and dynamic flow properties of in vivosystems. However, microfluidic devices can capture features of the native vasculature such as cellular composition, flow, geometry, and extracellular matrix presentation. This review, although not comprehensive, highlights microfluidic approaches that aim to improve our current understanding of the pathophysiological mechanisms surrounding SCD. Microfluidic platforms can aid in identifying factors that may contribute to disease severity and can serve as suitable testbeds for novel treatment strategies which may improve patient outcomes.
Renita E. Horton Accepted manuscript online: 4 April 2017 DOI: 10.1111/micc.12373