Evidence map›Paper›PMID 38548938›Full record

ArticleNature protocols2024

Standardized production of hPSC-derived cardiomyocyte aggregates in stirred spinner flasks.

Nils Kriedemann, Wiebke Triebert, Jana Teske, Mira Mertens, Annika Franke, Kevin Ullmann, Felix Manstein, Lika Drakhlis, Alexandra Haase, Caroline Halloin and 2 more

Abstract read
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In one paragraph

Article in Nature protocols, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
7.5field-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

23 citing papers in PubMed, 32 citations in OpenAlex.

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  8. Beyond monolayers: a comparative analysis of 2D cell cultures and 3DFrontiers in bioengineering and biotechnology · 2026
    Review
  9. Article
  10. Pluripotent stem cell-based approaches for heart repair and the potential of genetic modifications.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  11. Review
  12. Article
  13. Generation and applications of cardiac spheroids.npj biomedical innovations · 2025
    Review
  14. Article
  15. 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

12 authors at 2 institutions in 2 countries.

Nils Kriedemann *Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany. kriedemann.nils@mh-hannover.de.ORCID 0000-0001-7767-1556
Wiebke Triebert *Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.
Jana TeskeDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.
Mira MertensDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.
Annika FrankeDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.
Kevin UllmannDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.ORCID 0000-0001-5543-527X
Felix MansteinDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.ORCID 0000-0001-9740-9686
Lika DrakhlisDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.ORCID 0000-0003-2424-1127
Alexandra HaaseDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.ORCID 0000-0003-2666-4297
Caroline HalloinDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.
Ulrich MartinDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany.ORCID 0000-0003-1058-4540
Robert ZweigerdtDepartment of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO); REBIRTH-Research Center for Translational Regenerative Medicine; Hannover Medical School (MHH), Hannover, Germany. zweigerdt.robert@mh-hannover.de.ORCID 0000-0002-4656-0770
Medizinische Hochschule Hannover · DENovo Nordisk (Denmark) · DK

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01EK1601A, 13XP5092B, 031L0249, 01EK2108ADeutsche Forschungsgemeinschaft (German Research Foundation) REBIRTH EXC 62/2, ZW64/4-2European Commission (EC) 101056712Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture) ZN3340, ZN4092
6 · The paper itself

Abstract

A promising cell-therapy approach for heart failure aims at differentiating human pluripotent stem cells (hPSCs) into functional cardiomyocytes (CMs) in vitro to replace the disease-induced loss of patients' heart muscle cells in vivo. But many challenges remain for the routine clinical application of hPSC-derived CMs (hPSC-CMs), including good manufacturing practice (GMP)-compliant production strategies. This protocol describes the efficient generation of hPSC-CM aggregates in suspension culture, emphasizing process simplicity, robustness and GMP compliance. The strategy promotes clinical translation and other applications that require large numbers of CMs. Using a simple spinner-flask platform, this protocol is applicable to a broad range of users with general experience in handling hPSCs without extensive know-how in biotechnology. hPSCs are expanded in monolayer to generate the required cell numbers for process inoculation in suspension culture, followed by stirring-controlled formation of cell-only aggregates at a 300-ml scale. After 48 h at checkpoint (CP) 0, chemically defined cardiac differentiation is induced by WNT-pathway modulation through use of the glycogen-synthase kinase-3 inhibitor CHIR99021 (WNT agonist), which is replaced 24 h later by the chemical WNT-pathway inhibitor IWP-2. The exact application of the described process parameters is important to ensure process efficiency and robustness. After 10 d of differentiation (CP I), the production of ≥100 × 10

Indexed as

Cell Culture TechniquesCell DifferentiationMyocytes, CardiacPluripotent Stem CellsHumans

Identifiers

PMID38548938
OpenAlexW4393258316

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.