Red blood cells as delivery vessels for exerkines: A novel transfusion-based strategyOA

Dear Editor,Recent translational perspectives highlight the therapeutic potential of exercise-conditioned plasma,which is now considered ready for early-phase clinical trials across various non-communicable diseases,including cancer and Alzheimer''s disease,given the well-established benefits of exercise.1,2 Despite these promising advances in plasma transfusion,we propose a more refined approach using washed and filtered red blood cells(RBC)from regularly exercising donors as the primary therapeutic vehicle to deliver the health-promoting effects of exercise in patients.This hypothesis is grounded in the unique biology of the RBC.The RBC is not merely an inert carrier of oxygen.During its 120-day lifespan,RBCs continuously interact with the plasma milieu,actively sampling and accumulating circulating molecules.It has recently been highlighted that receptors,including toll-like receptor 9(TLR9)3 and multispecific chemokine receptors(DARC),4,5 allow RBCs and RBC-derived extracellular vesicles(RBC-EV)to interact with myokines,exercise-responsive miRNAs,and even metabolites,collectively known as exerkines,6 released during skeletal muscle contraction.While the direct binding mechanisms between RBCs and exerkines are still being fully mapped,RBCs and RBC-EVs may both function as a homeostatic''sink''for these circulating factors.7 Why focus on RBC instead of whole plasma?