Research output per year
Research output per year
Joan Sebastián Gallego-Murillo, Giulia Iacono, Luuk A.M. van der Wielen, Emile van den Akker, Marieke von Lindern*, Sebastian Aljoscha Wahl
Research output: Contribution to journal › Article › Scientific › peer-review
Transfusion of donor-derived red blood cells (RBCs) is the most common form of cell therapy. Production of transfusion-ready cultured RBCs (cRBCs) is a promising replacement for the current, fully donor-dependent therapy. A single transfusion unit, however, contains 2 × 1012 RBC, which requires large scale production. Here, we report on the scale-up of cRBC production from static cultures of erythroblasts to 3 L stirred tank bioreactors, and identify the effect of operating conditions on the efficiency of the process. Oxygen requirement of proliferating erythroblasts (0.55–2.01 pg/cell/h) required sparging of air to maintain the dissolved oxygen concentration at the tested setpoint (2.88 mg O2/L). Erythroblasts could be cultured at dissolved oxygen concentrations as low as 0.7 O2 mg/ml without negative impact on proliferation, viability or differentiation dynamics. Stirring speeds of up to 600 rpm supported erythroblast proliferation, while 1800 rpm led to a transient halt in growth and accelerated differentiation followed by a recovery after 5 days of culture. Erythroblasts differentiated in bioreactors, with final enucleation levels and hemoglobin content similar to parallel cultures under static conditions.
Original language | English |
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Pages (from-to) | 3096-3116 |
Journal | Biotechnology and Bioengineering |
Volume | 119 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2022 |
Research output: Thesis › Dissertation (TU Delft)