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Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells

Iron, supplemented as iron-loaded transferrin (holotransferrin), is an essential nutrient in mammalian cell cultures, particularly for erythroid cultures. The high cost of human transferrin represents a challenge for large scale production of red blood cells (RBCs) and for cell therapies in general....

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Autores principales: Gallego-Murillo, Joan Sebastián, Yağcı, Nurcan, Pinho, Eduardo Machado, Wahl, Sebastian Aljoscha, van den Akker, Emile, von Lindern, Marieke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147612/
https://www.ncbi.nlm.nih.gov/pubmed/37117329
http://dx.doi.org/10.1038/s41598-023-32706-1
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author Gallego-Murillo, Joan Sebastián
Yağcı, Nurcan
Pinho, Eduardo Machado
Wahl, Sebastian Aljoscha
van den Akker, Emile
von Lindern, Marieke
author_facet Gallego-Murillo, Joan Sebastián
Yağcı, Nurcan
Pinho, Eduardo Machado
Wahl, Sebastian Aljoscha
van den Akker, Emile
von Lindern, Marieke
author_sort Gallego-Murillo, Joan Sebastián
collection PubMed
description Iron, supplemented as iron-loaded transferrin (holotransferrin), is an essential nutrient in mammalian cell cultures, particularly for erythroid cultures. The high cost of human transferrin represents a challenge for large scale production of red blood cells (RBCs) and for cell therapies in general. 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 (Def(3)·Fe(3+), at 52 µmol/L) could eliminate the need for holotransferrin supplementation during in vitro expansion and differentiation of erythroblast cultures to produce large numbers of enucleated RBC. Only the first stage, when hematopoietic stem cells committed to erythroblasts, required holotransferrin supplementation. RBCs cultured in presence of Def(3)·Fe(3+) or holotransferrin (1000 µg/mL) were similar with respect to differentiation kinetics, expression of cell-surface markers CD235a and CD49d, hemoglobin content, and oxygen association/dissociation. Replacement of holotransferrin supplementation by Def(3)·Fe(3+) was also successful in cultures of myeloid cell lines (MOLM13, NB4, EOL1, K562, HL60, ML2). Thus, iron-loaded deferiprone can partially replace holotransferrin as a supplement in chemically defined cell culture medium. This holds promise for a significant decrease in medium cost and improved economic perspectives of the large scale production of red blood cells for transfusion purposes.
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spelling pubmed-101476122023-04-30 Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells Gallego-Murillo, Joan Sebastián Yağcı, Nurcan Pinho, Eduardo Machado Wahl, Sebastian Aljoscha van den Akker, Emile von Lindern, Marieke Sci Rep Article Iron, supplemented as iron-loaded transferrin (holotransferrin), is an essential nutrient in mammalian cell cultures, particularly for erythroid cultures. The high cost of human transferrin represents a challenge for large scale production of red blood cells (RBCs) and for cell therapies in general. 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 (Def(3)·Fe(3+), at 52 µmol/L) could eliminate the need for holotransferrin supplementation during in vitro expansion and differentiation of erythroblast cultures to produce large numbers of enucleated RBC. Only the first stage, when hematopoietic stem cells committed to erythroblasts, required holotransferrin supplementation. RBCs cultured in presence of Def(3)·Fe(3+) or holotransferrin (1000 µg/mL) were similar with respect to differentiation kinetics, expression of cell-surface markers CD235a and CD49d, hemoglobin content, and oxygen association/dissociation. Replacement of holotransferrin supplementation by Def(3)·Fe(3+) was also successful in cultures of myeloid cell lines (MOLM13, NB4, EOL1, K562, HL60, ML2). Thus, iron-loaded deferiprone can partially replace holotransferrin as a supplement in chemically defined cell culture medium. This holds promise for a significant decrease in medium cost and improved economic perspectives of the large scale production of red blood cells for transfusion purposes. Nature Publishing Group UK 2023-04-28 /pmc/articles/PMC10147612/ /pubmed/37117329 http://dx.doi.org/10.1038/s41598-023-32706-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gallego-Murillo, Joan Sebastián
Yağcı, Nurcan
Pinho, Eduardo Machado
Wahl, Sebastian Aljoscha
van den Akker, Emile
von Lindern, Marieke
Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells
title Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells
title_full Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells
title_fullStr Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells
title_full_unstemmed Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells
title_short Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells
title_sort iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147612/
https://www.ncbi.nlm.nih.gov/pubmed/37117329
http://dx.doi.org/10.1038/s41598-023-32706-1
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