Kadari, Asifiqbal, Mekala, SubbaRao, Wagner, Nicole, Malan, Daniela, Koeth, Jessica, Doll, Katharina, Stappert, Laura, Eckert, Daniela, Peitz, Michael, Matthes, Jan ORCID: 0000-0003-2754-1555, Sasse, Philipp ORCID: 0000-0002-8502-9472, Herzig, Stefan, Bruestle, Oliver, Erguen, Suleyman and Edenhofer, Frank ORCID: 0000-0002-6489-714X (2015). Robust Generation of Cardiomyocytes from Human iPS Cells Requires Precise Modulation of BMP and WNT Signaling. Stem Cell Rev. Rep., 11 (4). S. 560 - 570. TOTOWA: HUMANA PRESS INC. ISSN 1558-6804

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Abstract

Various strategies have been published enabling cardiomyocyte differentiation of human induced pluripotent stem (iPS) cells. However the complex nature of signaling pathways involved as well as line-to-line variability compromises the application of a particular protocol to robustly obtain cardiomyocytes from multiple iPS lines. Hence it is necessary to identify optimized protocols with alternative combinations of specific growth factors and small molecules to enhance the robustness of cardiac differentiation. Here we focus on systematic modulation of BMP and WNT signaling to enhance cardiac differentiation. Moreover, we improve the efficacy of cardiac differentiation by enrichment via lactate. Using our protocol we show efficient derivation of cardiomyocytes from multiple human iPS lines. In particular we demonstrate cardiomyocyte differentiation within 15 days with an efficiency of up to 95 % as judged by flow cytometry staining against cardiac troponin T. Cardiomyocytes derived were functionally validated by alpha-actinin staining, transmission electron microscopy as well as electrophysiological analysis. We expect our protocol to provide a robust basis for scale-up production of functional iPS cell-derived cardiomyocytes that can be used for cell replacement therapy and disease modeling.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kadari, AsifiqbalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mekala, SubbaRaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malan, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeth, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doll, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stappert, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckert, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peitz, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matthes, JanUNSPECIFIEDorcid.org/0000-0003-2754-1555UNSPECIFIED
Sasse, PhilippUNSPECIFIEDorcid.org/0000-0002-8502-9472UNSPECIFIED
Herzig, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruestle, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erguen, SuleymanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edenhofer, FrankUNSPECIFIEDorcid.org/0000-0002-6489-714XUNSPECIFIED
URN: urn:nbn:de:hbz:38-398429
DOI: 10.1007/s12015-014-9564-6
Journal or Publication Title: Stem Cell Rev. Rep.
Volume: 11
Number: 4
Page Range: S. 560 - 570
Date: 2015
Publisher: HUMANA PRESS INC
Place of Publication: TOTOWA
ISSN: 1558-6804
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PLURIPOTENT STEM-CELLS; PROMOTES CARDIAC DIFFERENTIATION; SMALL-MOLECULE; HEART; MOUSE; POPULATION; INDUCTION; ENHANCE; DISEASEMultiple languages
Cell & Tissue Engineering; Cell Biology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39842

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