Chalcone‐Supported Cardiac Mesoderm Induction in Human Pluripotent Stem Cells for Heart Muscle Engineering

Autor: Lutz F. Tietze, James E. Hudson, Ravi Gandamala, Bhakti Irene Seth, Taukeer A. Khan, Farah Raad, Tilman Uli Esser, Buntaro Fujita, Wolfram-Hubertus Zimmermann
Rok vydání: 2021
Předmět:
pharmacology [Chalcones]
cardiac differentiation
metabolism [Mesoderm]
Biochemistry
Mesoderm
chemistry.chemical_compound
0302 clinical medicine
drug effects [Pluripotent Stem Cells]
Drug Discovery
human pluripotent stem cells
General Pharmacology
Toxicology and Pharmaceutics
Induced pluripotent stem cell
0303 health sciences
Full Paper
Molecular Structure
Full Papers
3. Good health
Cell biology
medicine.anatomical_structure
Bone morphogenetic protein 4
embryonic structures
Molecular Medicine
chemistry [Chalcones]
Signal transduction
Stem cell
Pluripotent Stem Cells
cytology [Myocardium]
Chalcone
metabolism [Pluripotent Stem Cells]
BMP signaling
Phenotypic screening
Structure-Activity Relationship
03 medical and health sciences
Directed differentiation
medicine
Humans
ddc:610
030304 developmental biology
Pharmacology
drug effects [Mesoderm]
Dose-Response Relationship
Drug
Tissue Engineering
chalcones
Myocardium
Organic Chemistry
chemistry
small-molecule screening
030217 neurology & neurosurgery
Zdroj: Chemmedchem
ChemMedChem 16(21), 3300-3305 (2021). doi:10.1002/cmdc.202100222
ISSN: 1860-7187
1860-7179
DOI: 10.1002/cmdc.202100222
Popis: Human pluripotent stem cells (hPSCs) hold great promise for applications in cell therapy and drug screening in the cardiovascular field. Bone morphogenetic protein 4 (BMP4) is key for early cardiac mesoderm induction in hPSC and subsequent cardiomyocyte derivation. Small‐molecular BMP4 mimetics may help to standardize cardiomyocyte derivation from hPSCs. Based on observations that chalcones can stimulate BMP4 signaling pathways, we hypothesized their utility in cardiac mesoderm induction. To test this, we set up a two‐tiered screening strategy, (1) for directed differentiation of hPSCs with commercially available chalcones (4’‐hydroxychalcone [4’HC] and Isoliquiritigen) and 24 newly synthesized chalcone derivatives, and (2) a functional screen to assess the propensity of the obtained cardiomyocytes to self‐organize into contractile engineered human myocardium (EHM). We identified 4’HC, 4‐fluoro‐4’‐methoxychalcone, and 4‐fluoro‐4’‐hydroxychalcone as similarly effective in cardiac mesoderm induction, but only 4’HC as an effective replacement for BMP4 in the derivation of contractile EHM‐forming cardiomyocytes.
Have a little heart: A screen for mesoderm inducing chalcones in human pluripotent stem cell cultures identified 4’‐hydroxychalcone (4’HC) as an effective replacement for bone‐morphogenetic protein 4 (BMP4) in supporting the derivation of engineered heart muscle (EHM)‐formation competent cardiomyocytes.
Databáze: OpenAIRE
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