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High density bioprocessing of human pluripotent stem cells by metabolic control and in silico modeling

التفاصيل البيبلوغرافية
العنوان: High density bioprocessing of human pluripotent stem cells by metabolic control and in silico modeling
المؤلفون: Felix Manstein, Kevin Ullmann, Christina Kropp, Caroline Halloin, Wiebke Triebert, Annika Franke, Clara‐Milena Farr, Anais Sahabian, Alexandra Haase, Yannik Breitkreuz, Michael Peitz, Oliver Brüstle, Stefan Kalies, Ulrich Martin, Ruth Olmer, Robert Zweigerdt
المصدر: Stem Cells Translational Medicine, Vol 10, Iss 7, Pp 1063-1080 (2021)
بيانات النشر: Oxford University Press, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine (General)
LCC:Cytology
مصطلحات موضوعية: high density culture, human pluripotent stem cells, in silico process modeling, process scale‐up, stirred tank bioreactor, suspension culture, Medicine (General), R5-920, Cytology, QH573-671
الوصف: Abstract To harness the full potential of human pluripotent stem cells (hPSCs) we combined instrumented stirred tank bioreactor (STBR) technology with the power of in silico process modeling to overcome substantial, hPSC‐specific hurdles toward their mass production. Perfused suspension culture (3D) of matrix‐free hPSC aggregates in STBRs was applied to identify and control process‐limiting parameters including pH, dissolved oxygen, glucose and lactate levels, and the obviation of osmolality peaks provoked by high density culture. Media supplements promoted single cell‐based process inoculation and hydrodynamic aggregate size control. Wet lab‐derived process characteristics enabled predictive in silico modeling as a new rational for hPSC cultivation. Consequently, hPSC line‐independent maintenance of exponential cell proliferation was achieved. The strategy yielded 70‐fold cell expansion in 7 days achieving an unmatched density of 35 × 106 cells/mL equivalent to 5.25 billion hPSC in 150 mL scale while pluripotency, differentiation potential, and karyotype stability was maintained. In parallel, media requirements were reduced by 75% demonstrating the outstanding increase in efficiency. Minimal input to our in silico model accurately predicts all main process parameters; combined with calculation‐controlled hPSC aggregation kinetics, linear process upscaling is also enabled and demonstrated for up to 500 mL scale in an independent bioreactor system. Thus, by merging applied stem cell research with recent knowhow from industrial cell fermentation, a new level of hPSC bioprocessing is revealed fueling their automated production for industrial and therapeutic applications.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2157-6580
2157-6564
Relation: https://doaj.org/toc/2157-6564; https://doaj.org/toc/2157-6580
DOI: 10.1002/sctm.20-0453
URL الوصول: https://doaj.org/article/c7121fae9196446f87e88d0aaf778d3a
رقم الأكسشن: edsdoj.7121fae9196446f87e88d0aaf778d3a
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:21576580
21576564
DOI:10.1002/sctm.20-0453