Large‐scale production of red blood cells from stem cells: What are the technical challenges ahead?

Abstract

Blood-transfusion centers regularly face the challenge of donor blood shortages, especially for rare blood groups. The possibility of producing universal red blood cells from stem cells industrially has become a possible alternative since the successful injection of blood generated in vitro into a human being in 2011. Although there remains many biological and regulatory issues concerning the efficacy and safety of this new product, the major challenge today for future clinical applications is switching from the current limited 2-dimensional production techniques to large-scale 3-dimensional bioreactors. In addition to requiring technological breakthroughs, the whole process also has to become at least five-fold more cost-efficient to match the current prices of high-quality blood products. The current review sums up the main biological advances of the past decade, outlines the key biotechnological challenges for the large-scale cost-effective production of red blood cells, proposes solutions based on strategies used in the bioindustry and presents the state-of-the-art of large-scale blood production.

Use of differentiated pluripotent stem cells in replacement therapy for treating disease

“…The derivation of HSC from human PSC has proven elusive, although several examples of low level engraftment have been reported(8–10). Although true HSCs are not yet available, methods exist to produce RBCs (11, 12) and platelets (13) in vitro that are suitable for transfusion. Ultimately, advances in in vitro cell manufacture should soon be able to reduce costs and enable an off-the-shelf supply.…”

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model

“…Stem cell-derived RBCs are being considered as a potential alternative to donor-derived red cell transfusion products [6, 7, 33, 34]. We characterized biochemical and functional parameters of RBCs derived from cord blood and compared those parameters to RBCs collected from healthy human volunteers.…”

“…A number of groups have developed protocols to stimulate differentiation of induced pluripotent stem cells or hematopoietic stem cells to mature into enucleated erythrocytes. While RBCs produced using these methods show much promise, the methods have generally suffered from low cell expansion rates or low enucleation frequency [6]. Due to recent refinements of the techniques, stemRBCs with similar morphology and hemoglobin function compared to donor-derived RBCs have been produced (for review, see [6, 7]).…”

“…While RBCs produced using these methods show much promise, the methods have generally suffered from low cell expansion rates or low enucleation frequency [6]. Due to recent refinements of the techniques, stemRBCs with similar morphology and hemoglobin function compared to donor-derived RBCs have been produced (for review, see [6, 7]). As a proof of concept of their clinical significance, Giarratana et al .…”

Blood, meat, and upscaling tissue engineering: Promises, anticipated markets, and performativity in the biomedical and agri-food sectors

“…Taking a similar line, Rousseau et al (2014) suggest that the current cost per unit for allo-immunized patients is $700-1200, and predict that this cost would also be met by health insurance companies in critical situations. This given, these prices are clearly below the current likely costs with Rousseau et al (2014) identifying a cultured blood cost of $3,000 per unit as the appropriate target which remains higher than even rare blood types at current prices. The anticipated economics of cultured meat are quite distinct, once again in the world of agri-food as opposed to healthcare.…”