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Small-scale bioreactor supports high density HEK293 cell perfusion culture for the production of recombinant Erythropoietin
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO. (Cell Technology Group (CETEG); Wallenberg Centre for Protein Research (WCPR), Stockholm, Sweden)ORCID iD: 0000-0002-0584-841X
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO. (Cell Technology Group (CETEG), Royal Institute of Technology (KTH), Stockholm, Sweden; Wallenberg Centre for Protein Research (WCPR), Stockholm, Sweden)ORCID iD: 0000-0002-0841-8845
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. (Cell Technology Group (CETEG), Royal Institute of Technology (KTH), Stockholm, Sweden; Wallenberg Centre for Protein Research (WCPR), Stockholm, Sweden)ORCID iD: 0000-0002-8309-6655
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. (Wallenberg Centre for Protein Research (WCPR), Stockholm, Sweden)ORCID iD: 0000-0003-1763-9073
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2020 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 309, p. 44-52Article in journal (Refereed) Published
Abstract [en]

Process intensification in mammalian cell culture-based recombinant protein production has been achieved by high cell density perfusion exceeding 10(8) cells/mL in the recent years. As the majority of therapeutic proteins are produced in Chinese Hamster Ovary (CHO) cells, intensified perfusion processes have been mainly developed for this type of host cell line. However, the use of CHO cells can result in non-human posttranslational modifications of the protein of interest, which may be disadvantageous compared with human cell lines. In this study, we developed a high cell density perfusion process of Human Embryonic Kidney (HEK293) cells producing recombinant human Erythropoietin (rhEPO). Firstly, a small-scale perfusion system from commercial bench-top screening bioreactors was developed for < 250 mL working volume. Then, after the first trial runs with CHO cells, the system was modified for HEK293 cells (more sensitive than CHO cells) to achieve a higher oxygen transfer under mild aeration and agitation conditions. Steady states for medium (20 x 10(6) cells/mL) and high cell densities (80 x 10(6) cells/mL), normal process temperature (37 degrees C) and mild hypothermia (33 degrees C) as well as different cell specific perfusion rates (CSPR) from 10 to 60 pL/cell/day were applied to study the performance of the culture. The volumetric productivity was maximized for the high cell density steady state but decreased when an extremely low CSPR of 10 pL/cell/day was applied. The shift from high to low CSPR strongly reduced the nutrient uptake rates. The results from our study show that human cell lines, such as HEK293 can be used for intensified perfusion processes.

Place, publisher, year, edition, pages
Elsevier, 2020. Vol. 309, p. 44-52
Keywords [en]
Chinese Hamster Ovary (CHO) cells, Erythropoietin, High cell density culture, Human embryonic kidney 239 (HEK293) cells, Perfusion process, Small-scale bioreactor
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:kth:diva-268782DOI: 10.1016/j.jbiotec.2019.12.017ISI: 000510824700005PubMedID: 31891733Scopus ID: 2-s2.0-85077033718OAI: oai:DiVA.org:kth-268782DiVA, id: diva2:1396342
Note

QC 20200226

Available from: 2020-02-26 Created: 2020-02-26 Last updated: 2020-02-26Bibliographically approved

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Schwarz, HubertZhang, YeZhan, CaijuanMalm, MagdalenaRockberg, Johan

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