3D capillary system offers a new approach to investigate obstruction of microvessels

3D capillary system offers a new approach to investigate obstruction of microvessels

Pioneering CRISPR therapy leaves two patients free of blood disease symptoms Normal red blood cells, which are shaped like a round rubber raft, get through smoothly by contorting themselves to look like slippers, parachutes or bells. They somehow seem to avoid touching the inside of the capillary. However, red blood cells infected with malaria are more rigid and knobby. When transversing the capillary region, they do not elongate very much. They also roll and tumble. Both their shape and motion increase their risk of adhering to the capillary and becoming trapped. Encountering the forces present in blood flow, infected red blood cells tend to be pushed more toward the capillary wall compared to their uninfected counterparts. This shoving aside also raises their likelihood of sticking. While most normal red blood cells passed through the narrowest regions of the capillary model without a hitch, those infected with certain malaria parasite variants steadily accumulate. Within minutes they can dam the capillary and stop the flow, trapping some normal red blood cells with them. The researchers performed additional analysis of the possible detrimental contributions of the knobs that appear on malaria-infected red blood cells. They concluded that the dynamic forces of blood flow on the infected cells, and the modifications in the red blood cells induced by the malaria parasite might play independent roles in the events leading to blockage of microvessels. So, for example, there is more gathering of infected cells near the exit from the capillaries, which is the spot where blood flow slows down and shear stresses are reduced. The scientists mentioned that two possible shortcomings of their 3D human microvessel model is that it was derived from cell types originating in larger blood vessels and that studying single-cell dynamics is challenging due to imprecise flow control. They hope that, with modifications, this fundamentally new approach to investigating obstruction of microvessels will assist in future therapeutic developments for blood-stage malaria, in the study of other conditions that might damage small blood vessels, and in transfusion medicine research on blood products. Source: University of Washington Health Sciences/UW Medicine Journal reference: Arakawa, C. et al . (2020) Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries. Science Advances. doi.



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