Increasing demand for blood transfusions, but also safety towards emerging diseases of these call for new technologies to obtain red blood cells (RBC) for transfusion. Using cell culture techniques, erythroblasts, the precursor of RBCs can be proliferated at a small scale. For medical applications, a massive scale-up is required. Not only in volume but also cost-efficiency. Using engineering approaches, especially modelling and bioreactor cultivation systems, a significant increase in cell density and final cell titre were achieved.