Exploring the Erythroid Culture Systems and the Potential Use of Their Products as Therapeutic Enzyme Carriers

Abstract

The main use of donated red blood cells (RBCs) is blood transfusion, a treatment which saves millions of lives per year, by counteracting anaemia caused by a myriad of different diseases or situations. For some types of patients, blood banks encounter difficulties in sourcing a safe and suitable supply. Examples of these are rare blood phenotypes and patients who have developed alloimmunity, due to undergoing multiple blood transfusions, such as sickle cell or beta-thalassemia patients. It is a goal of multiple research groups around the world to produce a replacement blood product comprised of cultured stem cells or erythroid-derived cell lines, to produce red blood cells manufactured in the laboratory to service this clinical need. Although the state-of-the-art methodology reported to date can only produce volumes of manufactured red blood cells (mRBCs) far below a standard adult donation, the laboratory production of mRBCs offers a novel opportunity to be modified as a vehicle for drugs delivery or for enzyme replacement therapy. Proof of principal manufacture of cultured red blood cells, containing an enzyme for use as a therapeutic, has been recently achieved for the theoretical treatment of Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). This report will provide an up-to-date assessment of the literature around the ex vivo generation of RBCs and then go on to assess the best disease candidate for producing a therapeutic in mRBCs. To the best of this author's knowledge, this is the first study that theoretically explored the possibility of applying the methodology of Meinders et al., (2020) for glucokinase (GCK) as a potential treatment for hyperglycaemia.