Universität zu Köln

Eldabah, Nermeen, Nembo, Erastus Nembu, Penner, Marina, Semmler, Judith, Swelem, Rania, Hassab, Amina, Molcanyi, Marek, Hescheler, Juergen and Nguemo, Filomain (2018). Altered Functional Expression of beta-Adrenergic Receptors in Rhesus Monkey Embryonic Stem Cell-Derived Cardiomyocytes. Stem Cells Dev., 27 (5). S. 336 - 347. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-8534

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Abstract

Pluripotent stem cells have demonstrated the potential to generate large numbers of functional cardiomyocytes (CMs) from different cell sources. Besides Wnt signaling, additional pathways are involved in early cardiac development and function. To date however, no study exists showing the effects of perturbing the canonical Wnt pathway using nonhuman primate embryonic stem (ES) cells. In this study, we investigated the effect of canonical Wnt inhibition during differentiation of nonhuman primate ES cell-derived CMs under defined, growth factor conditions. Rhesus monkey ES (rES) cells were differentiated into spontaneously beating CMs in the absence (control) or presence (treated) of Wnt inhibitor Dickkopf1 (DKK1), vascular endothelial growth factor, and basic fibroblast growth factor combined or added in a sequential manner during differentiation. Quantification and functional characterization of CMs were assessed by molecular and electrophysiological techniques. Analysis revealed no difference in average ratio of spontaneously beating clusters in both control and treated groups. However, the percentage of CMs was significantly reduced and the expressions of specific cardiac markers tested were also decreased in the treated group. Interestingly, we found that in CMs obtained from treated group, beta-adrenergic receptors (beta-ARs) were less expressed, their function was altered and electrophysiological studies revealed differences in action potential responsiveness to beta-AR stimulation. We demonstrated that the Wnt/beta-catenin pathway inhibitor, DKK1 associated with other growth factors repressed functional expression of beta-ARs in rES cell-derived CMs. Thus, control of this pathway in each cell line and source is important for proper basic research and further cell therapy applications.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Eldabah, Nermeen UNSPECIFIED UNSPECIFIED UNSPECIFIED Nembo, Erastus Nembu UNSPECIFIED UNSPECIFIED UNSPECIFIED Penner, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Semmler, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Swelem, Rania UNSPECIFIED UNSPECIFIED UNSPECIFIED Hassab, Amina UNSPECIFIED UNSPECIFIED UNSPECIFIED Molcanyi, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-196012
DOI:	10.1089/scd.2017.0053
Journal or Publication Title:	Stem Cells Dev.
Volume:	27
Number:	5
Page Range:	S. 336 - 347
Date:	2018
Publisher:	MARY ANN LIEBERT, INC
Place of Publication:	NEW ROCHELLE
ISSN:	1557-8534
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARDIAC DIFFERENTIATION; MOUSE; MODULATION; ACTIVATION; SIGNALS; PROTEIN Multiple languages Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19601