Process control and in silico modeling strategies for enabling high density culture of human pluripotent stem cells in stirred tank bioreactors

Felix Manstein; Kevin Ullmann; Wiebke Triebert; Robert Zweigerdt

doi:10.1016/j.xpro.2021.100988

Process control and in silico modeling strategies for enabling high density culture of human pluripotent stem cells in stirred tank bioreactors

STAR Protoc. 2021 Dec 9;2(4):100988. doi: 10.1016/j.xpro.2021.100988. eCollection 2021 Dec 17.

Authors

Felix Manstein^{1

2}, Kevin Ullmann^{1

2}, Wiebke Triebert^{1

2}, Robert Zweigerdt^{1

2}

Affiliations

¹ Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover, Germany.
² REBIRTH Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

Abstract

The routine therapeutic and industrial applications of human pluripotent stem cells (hPSCs) require their constant mass supply by robust, efficient, and economically viable bioprocesses. Our protocol describes the fully controlled expansion of hPSCs in stirred tank bioreactors (STBRs) enabling cell densities of 35 × 10⁶ cells/mL while reducing culture medium consumption by 75%. This is achieved by in silico process modeling and computable upscaling. We provide a detailed blueprint for systematic process development of hPSCs and their progenies. For complete details on the use and execution of this protocol, please refer to Manstein et al. (2021).

Keywords: Biotechnology and bioengineering; Cell culture; Stem Cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bioreactors*
Cell Culture Techniques / methods*
Cells, Cultured
Computer Simulation*
Culture Media / chemistry
Culture Media / metabolism
Humans
Pluripotent Stem Cells / cytology*

Substances

Culture Media