Evidence map›Paper›PMID 42393756›Full record

ArticleStem cell research & therapy2026

Differentiation of human induced pluripotent stem cells into cardiac valve cells using 2D and 3D differentiation protocols.

Z Farzaneh, A Brückner, B K Fleischmann, S Rieck

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Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Z FarzanehInstitute of Physiology 1, Medical Faculty, University of Bonn, Bonn, Germany.
A BrücknerInstitute of Physiology 1, Medical Faculty, University of Bonn, Bonn, Germany.
B K FleischmannInstitute of Physiology 1, Medical Faculty, University of Bonn, Bonn, Germany. bernd.fleischmann@uni-bonn.de.
S RieckInstitute of Physiology 1, Medical Faculty, University of Bonn, Bonn, Germany. srieck@uni-bonn.de.ORCID 0009-0002-6172-4478

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGiven the high relevance of human cardiac valve disease, recent research aims to differentiate human induced pluripotent stem cells (hiPSCs) into valve endothelial-like cells (VELCs) and, through endothelial-to-mesenchymal transition (EndMT), into valve interstitial-like cells (VILCs).

methodsHere, we modified a 2D differentiation protocol demonstrating that VEGF can serve as the sole driver for differentiating cardiac progenitor cells (CPCs) into VELCs. Next, we utilized the so-called GiWi protocol (inhibition of glycogen synthase kinase, followed by inhibition of the Wnt pathway) to derive VELCs from 3D endocardial spheres. To this aim, hiPSCs were first differentiated into cardiac progenitor (CP) spheres using CHIR99021 (12 µM) and IWP2 (5 µM). Subsequent treatment with E8 medium containing high-dose FGF2 (100 ng/ml) resulted in endocardial spheres enriched for VELCs. For EndMT induction, endocardial spheres were MACS-sorted for PECAM1

resultsUsing VEGF as main driver to differentiate CPCs into VELCs in 2D, the generated VELCs appeared stable over time, can be maintained in vitro and transdifferentiated into ACTA2

conclusionsOverall, we developed a 2D differentiation protocol that produces stable VELCs and a high percentage of VILCs upon EndMT induction. We also established a new, efficient, and cost-effective protocol for the 3D differentiation of endocardial spheres to better mimic a physiologically relevant environment, thereby enabling improved maturation.

Indexed as

Cell DifferentiationHeart ValvesInduced Pluripotent Stem CellsCell Culture TechniquesCell Culture Techniques, Three DimensionalEndothelial CellsEndothelial-Mesenchymal TransitionFibroblast Growth Factor 2HumansPyridinesPyrimidinesTransforming Growth Factor beta1Vascular Endothelial Growth Factor AChir 99021Fibroblast Growth Factor 2PyridinesPyrimidinesTransforming Growth Factor beta1Vascular Endothelial Growth Factor ADifferentiationEndocardial cellsEndothelial-to-mesenchymal transitionHuman induced pluripotent stem cellsValve endothelial-like cells

Identifiers

PMID42393756
PMCPMC13330356

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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.