Evidence map›Paper›PMID 33660952›Full record

ArticleStem cells translational medicine2021

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

Felix Manstein, Kevin Ullmann, Christina Kropp, Caroline Halloin, Wiebke Triebert, Annika Franke, Clara-Milena Farr, Anais Sahabian, Alexandra Haase, Yannik Breitkreuz and 6 more

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 104 citations in OpenAlex.

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  14. GMP Manufacturing of Allogenic iPSC-NK Cells for Immunotherapy.Advances in experimental medicine and biology · 2025
    Review
  15. Human Pluripotent Stem Cell Expansion in Stirred Tank Bioreactors.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Felix MansteinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.ORCID 0000-0001-9740-9686
Kevin UllmannLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.ORCID 0000-0001-5543-527X
Christina KroppLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Caroline HalloinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Wiebke TriebertLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Annika FrankeLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Clara-Milena FarrLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Anais SahabianLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Alexandra HaaseLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Yannik BreitkreuzInstitute of Reconstructive Neurobiology, University of Bonn Medical Faculty & University Hospital Bonn, Bonn, Germany.
Michael PeitzInstitute of Reconstructive Neurobiology, University of Bonn Medical Faculty & University Hospital Bonn, Bonn, Germany.ORCID 0000-0001-5777-4240
Oliver BrüstleInstitute of Reconstructive Neurobiology, University of Bonn Medical Faculty & University Hospital Bonn, Bonn, Germany.ORCID 0000-0002-1277-0980
Stefan KaliesInstitute of Quantum Optics, Leibniz University Hannover, Hannover, Germany.ORCID 0000-0003-3025-264X
Ulrich MartinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.ORCID 0000-0003-1058-4540
Ruth OlmerLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.
Robert ZweigerdtLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Germany.ORCID 0000-0002-4656-0770
Leibniz Association · DEUniversity of Bonn · DELeibniz University Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 × 10

Indexed as

Cell Culture TechniquesPluripotent Stem CellsBioreactorsCell DifferentiationComputer SimulationCulture MediaHumansCulture Mediahigh density culturehuman pluripotent stem cellsin silico process modelingprocess scale-upstirred tank bioreactorsuspension culture

Identifiers

PMID33660952
PMCPMC8235132
OpenAlexW3135162893

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.