High density bioprocessing of human pluripotent stem cells by metabolic control and in silico modeling.
high density culture
human pluripotent stem cells
in silico process modeling
process scale-up
stirred tank bioreactor
suspension culture
Journal
Stem cells translational medicine
ISSN: 2157-6580
Titre abrégé: Stem Cells Transl Med
Pays: England
ID NLM: 101578022
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
18
01
2021
received:
08
10
2020
accepted:
24
01
2021
pubmed:
5
3
2021
medline:
24
3
2022
entrez:
4
3
2021
Statut:
ppublish
Résumé
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 × 10
Identifiants
pubmed: 33660952
doi: 10.1002/sctm.20-0453
pmc: PMC8235132
doi:
Substances chimiques
Culture Media
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1063-1080Informations de copyright
© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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