Tissue engineering has shown and still shows the potential to improve quality of life, especially in the cell therapy industry. An area of interest is in the in vitro production of red blood cells (RBCs). Blood transfusion is one of the most widespread forms of cell-based therapy and has been in use for over 50 years. However, the World Health Organisation (WHO) aims for each country to have 10 units of donated blood for every 1000 people, but studies show more than 40 countries fail to meet the WHO’s standard (Weimer et al., 2019). As the supply of blood is not meeting the demand, another sustainable method may be required to subsidise the blood bank, such as in vitro production using bioreactors. The benefit of cultured red blood cells (cRBCs) is the low risk of alloimmunisation, guaranteed availability and disease-free blood due to the sterile production.
Bioreactors have been increasing in popularity within biotechnology, for instance in the production of antibodies, cells, and tissues for therapy, due to their ability to control environmental factors and nutrient levels, enabling optimisation of cell growth and cost reductions. This project will study and improve large-scale manufacture of cells, improving the cell therapy industry and addressing the shortage of donated blood.
The aim of this research is to design and optimize a bench-scale perfusion bioreactor to produce red blood cells (RBCs) from precursor cells. Synthesis of RBCs requires 2 stages: (1) proliferation of the precursor cells to achieve sufficient starting cell numbers, and (2) differentiation, where the precursor cells mature into a specialised RBC. The approach of the project is to design a bench-scale fluidised bed bioreactor (FBB) and focus on the different parameters and their effects on the proliferation and the differentiation of the cultured cells. Next, the scale-up of bioreactors will be studied, to establish the optimal design and operation for large-scale manufacturing of RBCs for clinical use. The results from the above will show how biological properties of the cell are affected by growth within the FBBs. Hydrodynamic data of the system such as minimum fluidisation velocity and pressure drop will be obtained and research on how these affect biological systems will be researched. These data will give the optimum conditions to operate the bioreactor for maximum growth and production of cRBCs.
The bioreactor that will be developed during this project will be a platform technology applicable for manufacturing other similar cell therapies. The findings for this project will be important and applicable for biochemical engineering and tissue engineering, which may improve the understanding of replication and differentiation of cells in bioreactors.