Universität zu Köln

Nemade, Harshal, Acharya, Aviseka, Chaudhari, Umesh ORCID: 0000-0002-7743-4371, Nembo, Erastus, Nguemo, Filomain ORCID: 0000-0002-2236-6797, Riet, Nicole, Abken, Hinrich, Hescheler, Juergen, Papadopoulos, Symeon and Sachinidis, Agapios (2020). Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells. Cells, 9 (3). BASEL: MDPI. ISSN 2073-4409

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Abstract

Application of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited by the challenges in their efficient differentiation. Recently, the Wingless (Wnt) signaling pathway has emerged as the key regulator of cardiomyogenesis. In this study, we evaluated the effects of cyclooxygenase inhibitors on cardiac differentiation of hPSCs. Cardiac differentiation was performed by adherent monolayer based method using 4 hPSC lines (HES3, H9, IMR90, and ES4SKIN). The efficiency of cardiac differentiation was evaluated by flow cytometry and RT-qPCR. Generated hPSC-CMs were characterised using immunocytochemistry, electrophysiology, electron microscopy, and calcium transient measurements. Our data show that the COX inhibitors Sulindac and Diclofenac in combination with CHIR99021 (GSK-3 inhibitor) efficiently induce cardiac differentiation of hPSCs. In addition, inhibition of COX using siRNAs targeted towards COX-1 and/or COX-2 showed that inhibition of COX-2 alone or COX-1 and COX-2 in combination induce cardiomyogenesis in hPSCs within 12 days. Using IMR90-Wnt reporter line, we showed that inhibition of COX-2 led to downregulation of Wnt signalling activity in hPSCs. In conclusion, this study demonstrates that COX inhibition efficiently induced cardiogenesis via modulation of COX and Wnt pathway and the generated cardiomyocytes express cardiac-specific structural markers as well as exhibit typical calcium transients and action potentials. These cardiomyocytes also responded to cardiotoxicants and can be relevant as an in vitro cardiotoxicity screening model.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nemade, Harshal UNSPECIFIED UNSPECIFIED UNSPECIFIED Acharya, Aviseka UNSPECIFIED UNSPECIFIED UNSPECIFIED Chaudhari, Umesh UNSPECIFIED orcid.org/0000-0002-7743-4371 UNSPECIFIED Nembo, Erastus UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED orcid.org/0000-0002-2236-6797 UNSPECIFIED Riet, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-342142
DOI:	10.3390/cells9030554
Journal or Publication Title:	Cells
Volume:	9
Number:	3
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROMOTES CARDIAC DIFFERENTIATION; IPSC-DERIVED CARDIOMYOCYTES; SIGNALING MOLECULES; PRIMITIVE STREAK; MESP1 EXPRESSION; CALCIUM SPARKS; OUTFLOW TRACT; IN-VIVO; WNT; MOUSE Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34214