Manufacture of red blood cells from stem cells

Abstract

Although the current system of blood transfusion is relatively safe and established within the UK, periodic shortages of certain blood groups and residual risks of emerging transfusion transmitted infections (TTIs) make an industrial manufacture process for the generation of red blood cells more desirable. The generation of red blood cells from human embryonic stem cells has been completed in vitro but the major challenge lies in making the process highly scalable and economically viable. Initially human embryonic and induced pluripotent stem cells were trialled for use on the project however these were found to be inconsistent, a major issue in cellular therapies. They were replaced with CD34+ cord blood stem cells which are morphologically and physiologically divergent. In order to assess their suitability for a GMP-complaint manufacturing process an ultra-scale down (microfluidic) approach was taken to assess the cells’ reactions to the changeable physical environment associated with scale-up procedures. Cellular responses to hypoxia and shear stress were evaluated at successive time-points in the step-wise haematopoietic differentiation process and recommendations made for optimum scale-up conditions. Conversely further challenges in the manufacture of red blood cells from stem cells were uncovered regarding the differences between stem cell derived red blood cells and their adult equivalents.