Print Email Facebook Twitter Expansion and differentiation of ex vivo cultured erythroblasts in scalable stirred bioreactors Title Expansion and differentiation of ex vivo cultured erythroblasts in scalable stirred bioreactors Author Gallego Murillo, Joan Sebastián (TU Delft BT/Bioprocess Engineering) Iacono, Giulia (Amsterdam UMC) van der Wielen, L.A.M. (TU Delft BT/Bioprocess Engineering; University of Limerick) van den Akker, Emile (Amsterdam UMC) von Lindern, Marieke (Amsterdam UMC) Wahl, S.A. (TU Delft BT/Industriele Microbiologie) Date 2022 Abstract 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. Subject cell culturecultured blooderythropoiesisred blood cellscale-upstirred tank bioreactor To reference this document use: http://resolver.tudelft.nl/uuid:1493e607-de5c-4557-8c1e-754dc8150dc6 DOI https://doi.org/10.1002/bit.28193 ISSN 0006-3592 Source Biotechnology and Bioengineering, 119 (11), 3096-3116 Part of collection Institutional Repository Document type journal article Rights © 2022 Joan Sebastián Gallego Murillo, Giulia Iacono, L.A.M. van der Wielen, Emile van den Akker, Marieke von Lindern, S.A. Wahl Files PDF Biotech_Bioengineering_20 ... sts_in.pdf 3.41 MB Close viewer /islandora/object/uuid:1493e607-de5c-4557-8c1e-754dc8150dc6/datastream/OBJ/view