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

2013 ◽  
Vol 9 (1) ◽  
pp. 28-38 ◽  
Author(s):  
Guillaume F. Rousseau ◽  
Marie-Catherine Giarratana ◽  
Luc Douay
2006 ◽  
Vol 34 (12) ◽  
pp. 1635-1642 ◽  
Author(s):  
Emmanuel N. Olivier ◽  
Caihong Qiu ◽  
Michelle Velho ◽  
Rhoda Elison Hirsch ◽  
Eric E. Bouhassira

2021 ◽  
Author(s):  
Joan Sebastián Gallego-Murillo ◽  
Nurcan Yağcı ◽  
Eduardo Machado Pinho ◽  
Adrián Abeijón-Valle ◽  
Aljoscha Wahl ◽  
...  

Iron is an essential nutrient in mammalian cell cultures, conventionally supplemented as iron-loaded transferrin (holotransferrin). The high cost of human transferrin represents a challenge for the large scale production of cell therapies, such as cultured red blood cells. We evaluated the use of deferiprone, a cell membrane-permeable drug for iron chelation therapy, as an iron carrier for erythroid cultures. Iron-loaded deferiprone (Def3·Fe3+) at a concentration of 52μmol/L could fully replace holotransferrin during erythroblast differentiation into reticulocytes, the erythroid differentiation stage with maximal iron requirements. Reticulocytes cultured in presence of Def3·Fe3+ or holotransferrin (1000μg/mL) were similar with respect to expression of cell-surface markers CD235a and CD49d, hemoglobin content, and oxygen association/dissociation. Def3·Fe3+ also supported expansion of the erythroid compartment in vitro, except for the first stage when hematopoietic stem cells committed to erythroblasts, in which a reduced erythroblasts yield was observed. This suggests that erythroblasts acquired the potential to process Def3·Fe3+ as iron source for biosynthesis pathways. Replacement of holotransferrin by Def3·Fe3+ was also successful in cultures of six myeloid cell lines (MOLM13, NB4, EOL1, K562, HL60, ML2). These results suggest that iron-loaded deferiprone can partially replace holotransferrin in chemically defined medium formulations for the production of cultured reticulocytes and proliferation of selected myeloid cell lines. This would lead to a significant decrease in medium cost that would improve the economic perspectives of the large scale production of red blood cells for transfusion purposes.


Hepatology ◽  
2020 ◽  
Vol 72 (1) ◽  
pp. 257-270 ◽  
Author(s):  
Kerstin Schneeberger ◽  
Natalia Sánchez‐Romero ◽  
Shicheng Ye ◽  
Frank G. Steenbeek ◽  
Loes A. Oosterhoff ◽  
...  

2008 ◽  
pp. 110306231138043
Author(s):  
Francesco D'andrea ◽  
Francesco De Francesco ◽  
Giuseppe A. Ferraro ◽  
Vincenzo Desiderio ◽  
Virginia Tirino ◽  
...  

2012 ◽  
Vol 59 (2) ◽  
pp. 106-120 ◽  
Author(s):  
Sunghoon Jung ◽  
Krishna M. Panchalingam ◽  
Reynold D. Wuerth ◽  
Lawrence Rosenberg ◽  
Leo A. Behie

2020 ◽  
Author(s):  
Magnus A. G. Hoffmann ◽  
Collin Kieffer ◽  
Pamela J. Bjorkman

AbstractEngineered red blood cells (RBCs) expressing viral receptors could be used therapeutically as viral traps as RBCs lack nuclei and other organelles required for viral replication. Here we show that the combination of a powerful erythroid-specific expression system and transgene codon optimization yields high expression levels of the HIV-1 receptors CD4 and CCR5, as well as a CD4-glycophorin A (CD4-GpA) fusion protein on enucleated RBCs. Engineered RBCs expressing CD4 and CCR5 were efficiently infected by HIV-1, but CD4 or CD4-GpA expression in the absence of CCR5 was sufficient to potently neutralize HIV-1 in vitro. To facilitate continuous large-scale production of engineered RBCs, we generated erythroblast cell lines stably expressing CD4-GpA or ACE2-GpA fusion proteins, which produced potent RBC viral traps against HIV-1 and SARS-CoV-2. Our results suggest that this approach warrants further investigation as a potential treatment against viral infections.


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