Evidence map›Paper›PMID 31444389›Full record

ArticleScientific reports2019

Automated real-time monitoring of human pluripotent stem cell aggregation in stirred tank reactors.

Ivo Schwedhelm, Daniela Zdzieblo, Antje Appelt-Menzel, Constantin Berger, Tobias Schmitz, Bernhard Schuldt, Andre Franke, Franz-Josef Müller, Ole Pless, Thomas Schwarz and 3 more

Erratum issuedAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Review
  2. Article
  3. Advancements in theFrontiers in toxicology · 2025
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  14. Article
  15. End-to-End Platform for Human Pluripotent Stem Cell Manufacturing.International journal of molecular sciences · 2019
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Ivo SchwedhelmUniversity Hospital Würzburg, Department Tissue Engineering and Regenerative Medicine (TERM), 97070, Würzburg, Germany.
Daniela ZdziebloUniversity Hospital Würzburg, Department Tissue Engineering and Regenerative Medicine (TERM), 97070, Würzburg, Germany.ORCID http://orcid.org/0000-0002-6606-2445
Antje Appelt-MenzelUniversity Hospital Würzburg, Department Tissue Engineering and Regenerative Medicine (TERM), 97070, Würzburg, Germany.
Constantin BergerUniversity Hospital Würzburg, Department Tissue Engineering and Regenerative Medicine (TERM), 97070, Würzburg, Germany.
Tobias SchmitzUniversity Hospital Würzburg, Department Tissue Engineering and Regenerative Medicine (TERM), 97070, Würzburg, Germany.
Bernhard SchuldtUniversity Hospital Schleswig-Holstein, Department of Psychiatry and Psychotherapy, 24105, Kiel, Germany.
Andre FrankeUniversity Hospital Schleswig-Holstein, Institute of Clinical Molecular Biology, 24105, Kiel, Germany.ORCID http://orcid.org/0000-0003-1530-5811
Franz-Josef MüllerUniversity Hospital Schleswig-Holstein, Department of Psychiatry and Psychotherapy, 24105, Kiel, Germany.
Ole PlessFraunhofer Institute for Molecular Biology and Applied Ecology IME, 22525, Hamburg, Germany.ORCID http://orcid.org/0000-0002-1468-316X
Thomas SchwarzTranslational Center for Regenerative Therapies, Fraunhofer Institute for Silicate Research ISC, 97070, Würzburg, Germany.
Philipp WiedemannMannheim University of Applied Sciences, Institute of Molecular and Cell Biology, 68163, Mannheim, Germany.
Heike WallesUniversity Hospital Würzburg, Department Tissue Engineering and Regenerative Medicine (TERM), 97070, Würzburg, Germany.
Jan HansmannUniversity Hospital Würzburg, Department Tissue Engineering and Regenerative Medicine (TERM), 97070, Würzburg, Germany. Jan.Hansmann@uni-wuerzburg.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The culture of human induced pluripotent stem cells (hiPSCs) at large scale becomes feasible with the aid of scalable suspension setups in continuously stirred tank reactors (CSTRs). Innovative monitoring options and emerging automated process control strategies allow for the necessary highly defined culture conditions. Next to standard process characteristics such as oxygen consumption, pH, and metabolite turnover, a reproducible and steady formation of hiPSC aggregates is vital for process scalability. In this regard, we developed a hiPSC-specific suspension culture unit consisting of a fully monitored CSTR system integrated into a custom-designed and fully automated incubator. As a step towards cost-effective hiPSC suspension culture and to pave the way for flexibility at a large scale, we constructed and utilized tailored miniature CSTRs that are largely made from three-dimensional (3D) printed polylactic acid (PLA) filament, which is a low-cost material used in fused deposition modelling. Further, the monitoring tool for hiPSC suspension cultures utilizes in situ microscopic imaging to visualize hiPSC aggregation in real-time to a statistically significant degree while omitting the need for time-intensive sampling. Suitability of our culture unit, especially concerning the developed hiPSC-specific CSTR system, was proven by demonstrating pluripotency of CSTR-cultured hiPSCs at RNA (including PluriTest) and protein level.

Indexed as

BioreactorsComputer SystemsAutomationCell AggregationCell ProliferationCells, CulturedComputer SimulationHumansInduced Pluripotent Stem CellsSuspensionsSuspensions

Identifiers

PMID31444389
PMCPMC6707254

What OpenQuestion holds

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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.