Project description
Observing and modelling circulating red blood cells may help us mimic them better
Red blood cells (RBCs) perform many functions critical to the well-being of all other cells in the body. Inadequate amounts of RBC or a disturbance in their function can have far-reaching detrimental impact. However, although RBCs have been quite well-studied in preparation, the mechanisms of their dynamic physiology as they travel throughout the body are largely unknown. This makes it impossible to know what properties engineered RBCs should have to truly mimic naturally produced ones. EVIDENCE is tackling this challenge with experimental and theoretical methods to evaluate RBCs under physiological flow conditions and in vivo. Outcomes may eventually support capabilities to safely supply RBCs globally via a functional in vitro spleen-on-a-chip.
Objective
After exiting the bone marrow, reticulocytes mature to form red blood cells (RBCs) which are highly adapted cells Red blood cells (RBCs) travel through our circulation during their entire lifetime of in average 120 days. This means they are in constant move and adapt to their surrounding by shape changes, e.g. when in high speed flow or with even more severe volume adaptations, when they squeeze through small capillaries or the slits of the spleen having less than half their own size. While on the move, RBCs have to deal with continuous changes in oxygen tension and pH, have to scavenge reactive oxygen species, and need to balance their responses towards the chemical and mechanical challenges. In contrast, most of the knowledge we gained about RBCs as well as diagnostic methods rely on RBCs in relative stasis, such as flux measurements, conventional patch-clamp, calorimetric assays, density centrifugation, atomic force microscopy, just to name a few. In the most extreme conditions the cells of investigation are even dead like in blood smears, electron microscopy or cyto-spins. Even if cells are on the move like in flow cytometers, they may rest in a drop of liquid. Furthermore, when taken from the circulation, the flow of the RBCs is suddenly terminated and (together with the application of anticoagulants) they experience a completely different environment that is likely to impair their properties.
The objective of EVIDENCE is the exploration of the properties and behaviour of RBCs under flow conditions and in vivo to understand pathophysiology and to design novel diagnostic devices. Theoretical models will help to understand these RBC properties and will enable the transfer of the gained knowledge into diagnostic devises in general and into the development of a spleen-on-the-chip in particular. Furthermore we aim to understand the effect of the flow in bioreactors, allowing the efficient production of RBCs in vitro with the goal to produce RBC for transfusion.
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Coordinator
66123 Saarbrucken
Germany