Evidence map›Paper›PMID 33558697›Full record

ArticleNature biotechnology2021

Human heart-forming organoids recapitulate early heart and foregut development.

Lika Drakhlis, Santoshi Biswanath, Clara-Milena Farr, Victoria Lupanow, Jana Teske, Katharina Ritzenhoff, Annika Franke, Felix Manstein, Emiliano Bolesani, Henning Kempf and 10 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2021. 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 259 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
259citing papers in PubMed, 2 pooled it
24.9field-weighted citation impact, top 1% 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

259 citing papers in PubMed, 2 syntheses or guidelines pooled it, 420 citations in OpenAlex.

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  4. Human cardiovascular organoids: Biomedical applications and ethical challenges.American heart journal plus : cardiology research and practice · 2026
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199 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 2 countries.

Lika DrakhlisLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany. drakhlis.lika@mh-hannover.de.ORCID http://orcid.org/0000-0003-2424-1127
Santoshi BiswanathLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Clara-Milena FarrLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Victoria LupanowLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Jana TeskeLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Katharina RitzenhoffLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Annika FrankeLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Felix MansteinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0001-9740-9686
Emiliano BolesaniLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
Henning KempfLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0003-2790-9137
Simone LiebscherDepartment of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany.
Katja Schenke-LaylandDepartment of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0001-8066-5157
Jan HegermannResearch Core Unit Electron Microscopy, Hannover Medical School, Hannover, Germany.
Lena NolteIndustrial and Biomedical Optics Department, Laser Zentrum Hannover, Hannover, Germany.
Heiko MeyerIndustrial and Biomedical Optics Department, Laser Zentrum Hannover, Hannover, Germany.
Jeanne de la RocheInstitute for Neurophysiology, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0001-5753-1732
Stefan ThiemannInstitute for Neurophysiology, Hannover Medical School, Hannover, Germany.
Christian Wahl-SchottInstitute for Neurophysiology, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0002-7514-2367
Ulrich MartinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0003-1058-4540
Robert ZweigerdtLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), REBIRTH-Research Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany. zweigerdt.robert@mh-hannover.de.ORCID http://orcid.org/0000-0002-4656-0770
Medizinische Hochschule Hannover · DELaser Zentrum Hannover · DENatural and Medical Sciences Institute · DENovo Nordisk (Denmark) · DKUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Organoid models of early tissue development have been produced for the intestine, brain, kidney and other organs, but similar approaches for the heart have been lacking. Here we generate complex, highly structured, three-dimensional heart-forming organoids (HFOs) by embedding human pluripotent stem cell aggregates in Matrigel followed by directed cardiac differentiation via biphasic WNT pathway modulation with small molecules. HFOs are composed of a myocardial layer lined by endocardial-like cells and surrounded by septum-transversum-like anlagen; they further contain spatially and molecularly distinct anterior versus posterior foregut endoderm tissues and a vascular network. The architecture of HFOs closely resembles aspects of early native heart anlagen before heart tube formation, which is known to require an interplay with foregut endoderm development. We apply HFOs to study genetic defects in vitro by demonstrating that NKX2.5-knockout HFOs show a phenotype reminiscent of cardiac malformations previously observed in transgenic mice.

Indexed as

Body PatterningEmbryonic DevelopmentGene Knockdown TechniquesGreen Fluorescent ProteinsHeartHepatocyte Nuclear Factor 4Homeobox Protein Nkx-2.5HumansIntestinesOrganoidsSequence Analysis, RNASOXB1 Transcription FactorsSOXF Transcription Factorsenhanced green fluorescent proteinGreen Fluorescent ProteinsHepatocyte Nuclear Factor 4HNF4A protein, humanHomeobox Protein Nkx-2.5NKX2-5 protein, humanSOX2 protein, humanSOXB1 Transcription FactorsSOXF Transcription Factors

Identifiers

PMID33558697
PMCPMC8192303
OpenAlexW3128197056

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.