Nemade, Harshal and Acharya, Aviseka and Chaudhari, Umesh and Nembo, Erastus and Nguemo, Filomain and Riet, Nicole and Abken, Hinrich and Hescheler, Juergen and Papadopoulos, Symeon and Sachinidis, Agapios (2020) Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells. CELLS, 9 (3): 554. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | PROMOTES CARDIAC DIFFERENTIATION; IPSC-DERIVED CARDIOMYOCYTES; SIGNALING MOLECULES; PRIMITIVE STREAK; MESP1 EXPRESSION; CALCIUM SPARKS; OUTFLOW TRACT; IN-VIVO; WNT; MOUSE; Pluripotent stem cells; Cardiomyocytes; Differentiation; Sulindac; Small molecules; Wnt pathway; Cyclooxygenase pathway |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 12:19 |
| Last Modified: | 29 Mar 2021 12:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44988 |
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