Culturing red blood cells from stem cells: a solution to present and future challenges of transfusion medicine?

Abstract

Transfusion needs are diversely fulfilled globally. Besides, with population ageing, the various problems faced by healthcare systems will become more and more prominent. As a consequence, the current model of blood supply has to be strengthened, and new sources of red blood cells (RBC) are welcome. A cell therapy approach, in which so‐called ‘cultured RBC’ (cRBC) are generated in vitro, might be a solution. We report here on the various obstacles that were overcome during the past decade to generate cRBC from various sources of stem cells (SC) and also discuss the next developments which will be required to achieve this goal. To date, the culmination point in the field has been the proof of principle of transfusion of cRBC into human, produced from autologous haematopoietic stem and progenitor cells (HSPC), which allowed to demonstrate a favourable life span of cRBC when compared with their native counterpart. The best available source of highly proliferative adult SC is cord blood (CB), which could allow to produce tens of RBC concentrates (RBCC) from one average CB. However, this source is quantitatively limited in number, and more research on HSPC isolated from peripheral blood (PB) is needed. In parallel, critical advances have allowed in vitro production of functional RBC from human pluripotent SC, either embryonic (ESC) or induced (iPS). As iPS can proliferate indefinitely and can be selected for a specific patient phenotype, they appear to be the most favourable SC source, but the protocols still need to be optimized. Most recently, erythroid cell lines have also been envisaged to produce RBC. The major challenges remaining today are economic and technological in order to lead to a cost‐effective process for large‐scale production.